Acute Cholangitis · Web of Medicine

On this page

Quick Reference

RxDrug of choicePiperacillin/tazobactam 4.5 g IV Q6H (for severe/healthcare-associated) or Ceftriaxone 2 g IV daily + Metronidazole 500 mg IV Q8H

AltAlternativesMeropenem 1 g IV Q8H (if ESBL suspected) or Levofloxacin 750 mg IV daily + Metronidazole

⊘AvoidAvoid elective cholecystectomy during the hyper-acute phase of sepsis before biliary decompression is achieved.

DxTest of choiceERCP (Diagnostic and Therapeutic); MRCP (Non-invasive diagnostic gold standard)

ScKey scoreTokyo Guidelines 2018 (TG18) Severity Grading

→When to referRefer to Interventional Gastroenterology or IR immediately for any Grade II or III disease requiring urgent decompression.

Acute cholangitis is a medical emergency; the combination of IV antibiotics and urgent biliary decompression (<24h) is mandatory to prevent death from biliary sepsis.

Acute cholangitis is a life-threatening clinical syndrome characterized by inflammation and infection of the biliary tree, typically resulting from the synergistic combination of biliary obstruction and bacterial proliferation. Historically defined by Charcot's triad (fever, jaundice, and right upper quadrant pain), modern diagnosis relies on the more sensitive [[Tokyo Guidelines 2018]] (TG18) criteria, which integrate systemic inflammatory markers, cholestatic laboratory findings, and cross-sectional imaging. The central pathophysiology involves a critical rise in intraductal pressure (>20 cm H2O), facilitating the translocation of enteric bacteria into the systemic circulation. Management is a medical-surgical emergency requiring aggressive fluid resuscitation, broad-spectrum antimicrobial therapy, and, most crucially, mechanical biliary decompression. Delays in decompression beyond 24 hours significantly increase mortality, which ranges from 1.2% in mild cases to over 8% in severe (Grade III) disease characterized by organ dysfunction.

Overview and Recommendations

Background

•Acute cholangitis represents a critical failure of the biliary-venous barrier, where intraductal pressures exceeding 20 cm H2O force bacteria and endotoxins directly into the hepatic venous sinuses and lymphatics. While the biliary tree is normally maintained at low pressures (7–14 cm H2O) and kept sterile by the flushing action of bile and secretory IgA, mechanical obstruction—most commonly from (gallstones), strictures, or malignancy—triggers rapid bacterial proliferation and systemic endotoxemia.
•The epidemiological landscape is bifurcating into two distinct high-risk populations: a geriatric cohort dominated by calculous disease (median age >80 years) and a younger, predominantly male cohort (median age ~48 years) with (PSC), often associated with . Iatrogenic triggers, particularly post- infections and -induced pseudolithiasis, represent increasingly common healthcare-associated causes that often involve multi-drug resistant organisms.
•Microbiological profiles are dominated by enteric Gram-negative rods, with (25–50%), species (15–20%), and species being the most frequent isolates. However, polymicrobial infections are common in patients with prior biliary-enteric anastomoses or indwelling stents, where species and anaerobes like play a significant role in driving systemic inflammatory response syndrome (SIRS).
•The paradigm shift from the historical Charcot's triad (1877) to the modern (TG18) has dramatically improved diagnostic sensitivity. While the classic triad is highly specific (~93%), it is absent in up to 50% of confirmed cases; the TG18 framework achieves a sensitivity >90% by incorporating laboratory markers like C-reactive protein (CRP) and advanced imaging findings to identify biliary sepsis before the onset of Reynolds' pentad (triad plus shock and altered mental status).

Evaluation

•Suspect acute cholangitis in any patient presenting with the classic triad of fever, jaundice, and right upper quadrant pain, but maintain a high index of clinical suspicion in elderly or immunocompromised patients who may present only with altered mental status or unexplained hypotension. Early recognition of biliary sepsis is vital, as the transition from localized infection to systemic shock can occur within hours of symptom onset.
•Examine the patient for signs of impending organ failure, specifically looking for tachycardia, hypotension (SBP < 90 mmHg), and tachypnea. Assess for septic encephalopathy (confusion or lethargy) and perform a thorough abdominal exam; while RUQ tenderness is common, the presence of guarding or rebound tenderness should prompt concern for concomitant or gallbladder perforation.
•Order immediate laboratory studies including a complete blood count (WBC), C-reactive protein (CRP), and a comprehensive metabolic panel (CMP) to evaluate liver function. Diagnostic thresholds under TG18 include a WBC < 4,000 or > 10,000/µL, CRP ≥ 1 mg/dL, and cholestatic markers such as serum bilirubin ≥ 2 mg/dL or alkaline phosphatase (ALP) > 1.5x the upper limit of normal.
•Obtain blood cultures (two sets) before initiating antibiotics, as they are positive in 20–30% of cases and guide narrowing of therapy. While bile cultures often yield more organisms, blood cultures are the primary tool for identifying the systemic pathogen driving the septic response.
•Perform transabdominal ultrasound as the initial imaging modality to screen for and biliary ductal dilation. While ultrasound is highly specific for stones, it has limited sensitivity for distal common bile duct (CBD) stones; therefore, a negative ultrasound in a patient with high clinical suspicion must be followed by more sensitive cross-sectional imaging.
•Order contrast-enhanced of the abdomen or if ultrasound is inconclusive or if malignancy is suspected. CT is superior for identifying the level of obstruction and complications like liver abscesses, while MRCP is the non-invasive gold standard for mapping the biliary tree and identifying subtle strictures or small stones.
•Apply the TG18 severity grading system immediately to dictate the timing of intervention. Grade III (Severe) is defined by any new organ dysfunction (e.g., PaO2/FiO2 < 300, Platelets < 100k, or need for vasopressors); Grade II (Moderate) includes patients with high fever (≥39°C), age ≥75, or bilirubin ≥5 mg/dL; Grade I (Mild) is a diagnosis of exclusion in those responding to initial therapy.
•Consider specialized testing if autoimmune etiologies are suspected, such as serum IgG4 levels for or p-ANCA for . In patients on immune checkpoint inhibitors (e.g., ), be alert for immune-related cholangitis which may present with concurrent hepatitis.

Management

•Initiate aggressive fluid resuscitation immediately following the Surviving Sepsis Campaign bundles, administering 30 mL/kg of balanced crystalloid (e.g., Lactated Ringer's) within the first 3 hours for patients with hypotension or lactate ≥ 4 mmol/L. Target a mean arterial pressure (MAP) ≥ 65 mmHg, utilizing norepinephrine if shock is refractory to fluids.
•Administer empiric broad-spectrum IV antibiotics within one hour of recognition. For community-acquired Grade I or II disease, 1–2 g daily plus 500 mg every 8 hours is appropriate; for Grade III or healthcare-associated cases, use 4.5 g every 6 hours to ensure coverage against and .
•Perform urgent biliary decompression within 24 hours for all patients with acute cholangitis, as this is the only definitive treatment for the septic focus. For Grade III (Severe) cases, decompression should ideally occur within 12 hours once the patient is hemodynamically stabilized.
•Utilize as the first-line modality for decompression. In the setting of sepsis-induced coagulopathy, prioritize simple biliary drainage (via plastic stent or nasobiliary tube) over endoscopic sphincterotomy (EST) to minimize the risk of procedural bleeding.
•Refer for (PTBD) or -guided biliary drainage (EUS-BD) if ERCP fails or is technically unfeasible due to altered surgical anatomy (e.g., Roux-en-Y gastric bypass). PTBD is particularly effective for high hilar (Klatskin) obstructions.
•Monitor for post-procedural complications, including , bleeding, and perforation. In patients with Grade III disease, continue intensive care monitoring for at least 24–48 hours post-decompression to ensure resolution of organ dysfunction.
•Tailor antibiotic therapy based on culture results once the patient is clinically stable. While the standard duration is 4–7 days, therapy may be shortened to 24–48 hours following successful and complete biliary drainage in uncomplicated calculous disease.
•Schedule definitive treatment of the underlying cause once the acute infection has resolved. For calculous disease, this typically involves a during the same hospital admission to prevent recurrent biliary events.
•Avoid the use of non-dihydropyridine calcium channel blockers or other drugs that may worsen biliary stasis during the acute phase. In patients with PSC, consider the long-term use of (UDCA) 13–15 mg/kg/day, though its role in preventing acute infectious episodes is limited.
•Discharge the patient only once they are afebrile for 24 hours, have a declining trend in inflammatory markers, and have achieved definitive biliary source control. Ensure a follow-up plan for repeat imaging or stent removal/exchange if temporary drainage was utilized.

Board Review — High Yield

•Charcot's Triad — Fever, Jaundice, RUQ pain (High specificity, low sensitivity for cholangitis).
•Reynolds' Pentad — Charcot's triad plus hypotension and altered mental status (indicates suppurative cholangitis and high mortality).
•20 cm H2O Rule — The critical intraductal pressure threshold for biliary-venous reflux and systemic bacterial translocation.
•Tokyo Guidelines 2018 — The current gold standard for diagnosis, requiring evidence of systemic inflammation, cholestasis, and imaging findings.
•Most Common Organism — Escherichia coli is the most frequently isolated pathogen in bile and blood cultures.
•Timing of ERCP — Urgent (<24h) decompression is associated with significantly lower mortality compared to delayed intervention.
•Primary Sclerosing Cholangitis (PSC) — A chronic risk factor for recurrent cholangitis, often associated with ulcerative colitis and an increased risk of cholangiocarcinoma.
•Ceftriaxone Pseudolithiasis — A known side effect where ceftriaxone precipitates with calcium in bile, potentially mimicking or causing biliary obstruction.

Deep Dive — Evidence Details

Definition, Classification, and Historical Context

▸Acute cholangitis is defined by the TG18 criteria as a combination of systemic inflammation, cholestasis, and biliary obstruction.
▸The historical Reynolds' pentad identifies the most severe form, Acute Suppurative Obstructive Cholangitis (AOSC), which carries a high risk of multi-organ failure.
▸Severity is graded from I to III based on the presence of organ dysfunction and the patient's response to initial therapy.

HY High Yield: Charcot's triad (fever, jaundice, RUQ pain) has high specificity but low sensitivity (~50-70%); the absence of the triad does not rule out acute cholangitis [8].

Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending from its junction with the duodenum. It tends to occur if the bile duct — Ascending cholangitis — Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending f...Wikipedia ↗

Acute cholangitis is a life-threatening clinical syndrome characterized by inflammation of the biliary tree, most commonly triggered by bacterial infection secondary to biliary stasis and obstruction ^[12]^D5. While historically viewed as a simple infection, modern understanding recognizes it as a complex interplay of mechanical stasis, increased intraductal pressure, and systemic inflammatory response ^[8]^B2b^[10]^C4.

Also Called / Synonyms:

Ascending cholangitis
Biliary sepsis
Acute suppurative obstructive cholangitis (AOSC)
Hepatic fever

Historical Evolution

The clinical recognition of acute cholangitis began with Jean-Martin Charcot in 1877, who described "hepatic fever" characterized by the classic triad of fever, jaundice, and right upper quadrant pain. This triad remains a hallmark of diagnosis, though its sensitivity is limited. In 1959, Reynolds and Dargan expanded this definition to include septic shock and altered mental status—collectively known as Reynolds' pentad—to describe Acute Suppurative Obstructive Cholangitis (AOSC) ^[10]^C4. AOSC represents a critical stage where purulent bile is under high pressure, necessitating immediate decompression to prevent multi-organ failure ^[8]^B2b^[10]^C4.

Modern Clinical Definition and Grading

The contemporary definition has shifted from purely clinical signs to the standardized framework of the Tokyo Guidelines 2018 (TG18). Under TG18, a definitive diagnosis requires evidence of systemic inflammation (fever or elevated inflammatory markers), cholestasis (jaundice or abnormal liver function tests), and biliary obstruction on imaging ^[7]^B3b^[8]^B2b. This framework also establishes a severity grading system that dictates the timing of intervention:

Grade I (Mild): Acute cholangitis that responds to initial medical treatment without meeting criteria for higher grades.
Grade II (Moderate): Cholangitis associated with factors such as leukocytosis (>12,000/mm³), high fever (≥39°C), advanced age (≥75 years), hyperbilirubinemia (total bilirubin ≥5 mg/dL), or hypoalbuminemia ^[8]^B2b.
Grade III (Severe): Cholangitis associated with at least one organ dysfunction (cardiovascular, neurological, respiratory, renal, hepatic, or hematological) ^[7]^B3b.

Classification and Variants

Acute cholangitis is classified primarily by its underlying etiology. While remains the most common cause (calculous cholangitis), several distinct variants and mimics exist, ranging from neoplastic obstructions to immune-mediated inflammatory conditions ^[4]^D5^[5]^D5^[11]^C4.

Variant	Key Distinguishing Feature	Associated Marker/Subtype
Calculous Cholangitis	Obstruction due to ; most common form ^[8]^B2b	Elevated CRP or NLR ^[7]^B3b
Malignant Cholangitis	Obstruction from tumors like or IPNB ^[4]^D5	Mucin production (IPNB) ^[4]^D5
Primary Sclerosing Cholangitis (PSC)	Chronic, immune-mediated fibro-inflammatory disease ^[3]^D5^[5]^D5	Large-duct vs. small-duct ^[1]^A1b^[2]^B2b
IgG4-Related Sclerosing Cholangitis	Biliary manifestation of ^[6]^D5	Elevated serum IgG4 ^[6]^D5
Iatrogenic/Post-Surgical	Occurs after ERCP or Kasai portoenterostomy ^[10]^C4^[12]^D5	Post-Kasai ( ) ^[12]^D5
Immune-Related (irAE)	Induced by checkpoint inhibitors (e.g., ) ^[11]^C4	Concurrent hepatitis/pancreatitis ^[11]^C4

Emerging etiologies include drug-induced biliary stasis, such as -induced pseudogallstones in rehabilitation patients ^[14]^C4. Rare mimics like hepatic Langerhans cell histiocytosis (LCH) can also present as sclerosing cholangitis, often requiring portal area histology for differentiation ^[9]^C4.

Pearl: The transition from Charcot’s triad to the TG18 criteria has improved diagnostic sensitivity, as the classic triad is absent in up to 50% of confirmed cases, yet its presence remains highly specific for biliary sepsis ^[8]^B2b.

Epidemiology and Risk Factors

▸PSC-related cholangitis predominantly affects males (up to 69%) with a median age of 48, whereas stone-related disease is common in the elderly (>80 years).
▸Ceftriaxone is a unique pharmacological risk factor for cholangitis due to the formation of calcium-ceftriaxone pseudogallstones.
▸Statin use is associated with a protective effect against acute cholangitis episodes in patients with primary sclerosing cholangitis.

HY High Yield: In patients with PSC, the presence of IBD not only increases the risk of colorectal cancer (HR 1.83) but also correlates with an earlier diagnosis of biliary disease [2, 27].

! Warning: Ceftriaxone-induced pseudolithiasis is a frequently overlooked cause of biliary obstruction in hospitalized elderly patients receiving prolonged antibiotic therapy [14, 29].

Incidence and prevalence of autoimmune-mediated biliary conditions are rising globally, contributing to a shifting landscape of acute cholangitis triggers ^[35]^D5. While remains the primary driver of biliary obstruction and subsequent infection, the increasing frequency of iatrogenic interventions and the rising prevalence of (PSC) have diversified the patient population at risk ^[17]^A1b^[35]^D5.

Demographic Distribution and Temporal Trends

Demographic profiles vary significantly based on the underlying etiology. In cohorts dominated by stone-related disease, the median age often exceeds 80 years, with a balanced sex distribution ^[14]^C4. Conversely, patients with PSC-related cholangitis are predominantly male (56%–69%) and present at a younger median age of 48 years ^[2]^B2b^[30]^B3b. PSC is diagnosed significantly earlier in patients with concurrent (IBD) compared to those with PSC alone ^[2]^B2b.

Temporal trends indicate an upward trajectory in the incidence of autoimmune liver diseases (AILD), including PSC and primary biliary cholangitis ^[35]^D5. In pediatric populations, cholangitis remains a critical complication following the Kasai procedure for and after (LT) ^[23]^B2a^[32]^B2a. Recurrence of PSC (rPSC) after LT is a significant challenge, with a high prevalence in patients who underwent transplantation for advanced immune-mediated cholestasis ^[19]^B2a^[34]^C4.

Iatrogenic and Procedural Risk Factors

Iatrogenic triggers, particularly (ERCP), represent a major risk for acute cholangitis. In LT recipients with biliary strictures, post-ERCP cholangitis is a frequent complication, even with prophylactic measures ^[33]^B3b. Single-dose antibiotic prophylaxis (e.g., 1 g or 400 mg) is often compared to multiday regimens to mitigate this risk, though optimal duration remains debated ^[25]^B3b.

Specific procedural techniques also influence risk. For instance, performing an endoscopic sphincterotomy (EST) during biliary drainage in patients with sepsis-induced coagulopathy (SIC) increases bleeding risk without providing clear clinical benefits over drainage alone ^[37]^B3b. In malignant obstruction, such as , the addition of intraluminal iodine-125 seed to biliary stenting may improve patency but requires careful monitoring for infectious complications ^[24]^A1a.

Pharmacological and Comorbid Risk Factors

Pharmacological agents can paradoxically increase biliary risk. Ceftriaxone use is associated with an increased risk of biliary infections due to pseudolithiasis caused by ceftriaxone-calcium precipitation ^[29]^B3b. This risk is particularly pronounced in geriatric rehabilitation patients, where ceftriaxone-induced pseudogallstones can lead to acute biliary events ^[14]^C4. Conversely, statin use has been identified as a protective factor, associated with a reduced risk of acute cholangitis in patients with PSC ^[30]^B3b.

Comorbidities such as IBD significantly elevate the risk of hepatobiliary complications. IBD increases the hazard ratio (HR) for to 1.83 (95% CI 1.52-2.21) in PSC patients, reflecting the high systemic inflammatory burden (NNT not calculable from reported data) ^[27]^B2b. Additionally, cirrhosis and advancing age are key determinants of hepatocellular carcinoma risk in the PSC population ^[31]^B2b.

Controversies and Guideline Disagreement

Question	Position A	Position B	Strength	Implication
Dominant Stricture in PSC	Endoscopic balloon dilation (EBD) is preferred due to fewer interventions (2.7 vs 6.5 per person) ^[22]^B2a.	Stent placement offers similar clinical efficacy (~85%) but higher complication rates ^[22]^B2a.	Moderate	EBD may reduce the cumulative risk of iatrogenic cholangitis.
Biliary Reconstruction in LT	Duct-to-duct (DD) reconstruction is standard in many centers ^[21]^B2a.	Roux-en-Y (RY) hepaticojejunostomy may be preferred in PSC to reduce recurrence ^[21]^B2a.	Low	Choice of technique impacts long-term biliary patency and infection risk.

Pearl: The of acute cholangitis is bifurcating into a geriatric, stone-driven population and a younger, male-predominant PSC-IBD population, with iatrogenic triggers like ERCP and ceftriaxone-induced pseudolithiasis representing critical modifiable risks ^[14]^C4^[29]^B3b^[30]^B3b^[35]^D5.

Risk Factors for Acute Cholangitis

Factor	Association (OR/HR/RR)	Evidence Level
Choledocholithiasis	Primary cause of obstruction	1b ^[17]^A1b
Ceftriaxone Use	Associated with pseudolithiasis	3b ^[29]^B3b
Post-Kasai Procedure	Significant complication in biliary atresia	2a ^[23]^B2a
Statin Use	Protective (Reduced risk in PSC)	3b ^[30]^B3b
IBD in PSC	HR 1.83 for CRC; high biliary morbidity	2b ^[2]^B2b^[27]^B2b
Gastritis/H. pylori	Potential trigger for AILD/PSC	2b ^[26]^B2b

Pathophysiology and Microbiology

▸Biliary-venous reflux occurs when intraductal pressure exceeds 20 cm H2O, facilitating the systemic translocation of bacteria and endotoxins.
▸Enteric organisms, particularly Escherichia coli and Klebsiella, are the primary pathogens, though anaerobes and Enterococcus are common in polymicrobial or healthcare-associated cases.
▸Microbiome-derived peptides like corisin and outer membrane vesicles (OMVs) from the gut-liver axis serve as key molecular drivers of cholangiocyte apoptosis and systemic inflammation.

HY High Yield: The most common organism isolated from both bile and blood cultures in acute cholangitis is **Escherichia coli**, followed by **Klebsiella** species [56].

! Warning: In patients with indwelling biliary stents or frequent ERCPs, the risk of polymicrobial infection and multidrug-resistant organisms (e.g., Pseudomonas, VRE) increases significantly [48, 56].

Intraductal pressures exceeding 20 cm H2O serve as the critical threshold for the systemic translocation of bacteria and endotoxins from the biliary tree into the bloodstream ^[56]^B2c^[61]^B3b. Under physiological conditions, bile is maintained at a low pressure (7–14 cm H2O) and is relatively sterile due to the flushing action of bile flow, the bacteriostatic properties of bile salts, and the presence of secretory IgA ^[42]^D5^[57]^B3b. When an obstruction—most commonly , strictures, or malignancy—interrupts this flow, the resulting stasis allows for bacterial proliferation and a rapid rise in pressure. Once this pressure surpasses the threshold for biliary-venous and biliary-lymphatic reflux, the patient transitions from localized biliary infection to systemic and sepsis ^[56]^B2c^[63]^D5.

The Mechanical-Infectious Synergy

The pathogenesis of acute cholangitis requires two concurrent factors: biliary stasis and the presence of bacteria in the bile (bacterbilia). In the setting of complete obstruction, such as an impacted stone at the ampulla, the intraductal pressure can rise to 30–50 cm H2O, forcing pathogens through the tight junctions of and into the hepatic venous sinuses ^[59]^D5^[61]^B3b. This mechanism is particularly aggressive in "recurrent pyogenic cholangitis" associated with hepatolithiasis, where a self-sustaining cycle of infection, stricture formation, and stone development perpetuates the disease ^[58]^D5. In severe gallstone pancreatitis, the impaction of stones at the ampulla of Vater can create a "common channel" that facilitates biliopancreatic reflux, further exacerbating the inflammatory response ^[59]^D5.

The Gut-Liver Axis and Bacterial Translocation

Pathogens typically enter the biliary system via retrograde migration from the duodenum, though portal venous translocation remains a significant secondary route ^[45]^D5. The integrity of the intestinal barrier is paramount; dysbiosis and "leaky gut" conditions allow gut pathobionts to release outer membrane vesicles (OMVs) that drive liver inflammation and fibrosis ^[55]^D5. These OMVs and other microbiome-derived products, such as the proapoptotic peptide corisin, are significantly elevated in the plasma and bile of patients with severe cholangitis ^[61]^B3b. Corisin, in particular, induces acute tissue injury by triggering cholangiocyte apoptosis, which further compromises the biliary barrier and facilitates systemic dissemination ^[61]^B3b.

Microbiology and Resistance Patterns

Biliary tract-associated bloodstream infections (BSI) are predominantly monomicrobial, though polymicrobial bile cultures are common in patients with prior biliary interventions or indwelling stents ^[56]^B2c^[48]^D5. Enteric Gram-negative rods are the most frequent isolates, reflecting the retrograde route of infection.

Organism Group	Common Pathogens	Clinical Significance
Gram-negative	Escherichia coli, Klebsiella spp., Enterobacter spp.	Most common; primary drivers of and sepsis ^[56]^B2c.
Gram-positive	Enterococcus spp., Streptococcus spp.	Often seen in polymicrobial infections or post-ERCP ^[48]^D5^[56]^B2c.
Anaerobes	Bacteroides fragilis, Clostridium spp.	Associated with complex strictures and prior biliary surgery ^[56]^B2c.
Emerging		Increasing prevalence in healthcare-associated cholangitis ^[56]^B2c.

Molecular Mediators of Injury

At the cellular level, are not passive conduits but active participants in the innate immune response. Upon exposure to pathogen-associated molecular patterns (PAMPs), these cells secrete pro-inflammatory cytokines, including IL-6 and TNF-α, and activate the IL-17 signaling pathway ^[38]^D5^[42]^D5. In chronic conditions like primary sclerosing cholangitis (PSC), this inflammatory milieu is further complicated by epigenetic alterations and aberrant immune activation, such as the recruitment of Th17 cells, which predispose the biliary tree to recurrent bouts of acute bacterial cholangitis ^[38]^D5^[51]^B3b^[66]^D5.

Controversies and Guideline Disagreement

Question	Traditional View	Emerging Evidence	Implication
Bile Sterility	Bile is sterile in healthy individuals.	16S rRNA sequencing reveals a distinct "biliary microbiome" even in health ^[40]^B2a^[57]^B3b.	Infection may arise from endogenous flora, not just retrograde migration.
Role of Anaerobes	Anaerobes are rare and don't require empiric coverage.	Anaerobes are present in up to 15% of severe cases and BSIs ^[56]^B2c.	Empiric anaerobic coverage is vital in Grade III (severe) disease.

Pearl: The transition from localized biliary infection to systemic sepsis is governed by the "20 cm H2O rule," where elevated intraductal pressure forces bacteria directly into the systemic circulation via biliary-venous reflux ^[56]^B2c^[61]^B3b.

Clinical Presentation and Physical Examination

▸Charcot's triad (fever, jaundice, RUQ pain) has high specificity (>90%) but poor sensitivity (<30%), making it an unreliable screening tool [75].
▸Reynolds' pentad (triad plus hypotension and altered mental status) indicates critical biliary sepsis and carries a high mortality risk [75].
▸Atypical presentations are common in the elderly and immunocompromised, who may present with isolated confusion or afebrile biliary obstruction [71, 84].

HY High Yield: In patients with suspected cholangitis and a history of immunotherapy, consider immune-mediated cholangitis (IMC). These patients often present with abdominal pain and fever but may require steroids rather than just antibiotics and drainage [69, 81].

! Warning: Do not wait for the full Charcot's triad to manifest before initiating a workup. The absence of jaundice does not exclude life-threatening cholangitis, especially in the early stages of obstruction [75].

Clinical recognition of biliary sepsis relies on identifying systemic inflammation alongside evidence of cholestasis, yet the classic diagnostic clusters often fail to manifest in early or complex cases. While the historical reliance on clinical signs persists in bedside teaching, modern diagnostic frameworks like the (TG18) have largely superseded them due to the low sensitivity of physical findings alone ^[75]^B3b^[76]^B2b.

Presenting Symptoms

Patients typically present with an acute onset of symptoms that progress rapidly over hours to days. The hallmark is Right Upper Quadrant (RUQ) pain, which is present in approximately 80% of cases, often described as constant, dull, or colicky if associated with migrating . Fever and chills are the most common systemic symptoms, reflecting the rapid translocation of bacteria into the systemic circulation once biliary pressure exceeds 20 cm H2O. In chronic conditions like (PSC), the presentation is more insidious; patients may remain asymptomatic for years or present with non-specific fatigue and pruritus before an acute infectious episode occurs ^[74]^D5^[83]^D5.

Systemic and Neurological Findings

In the context of acute cholangitis, the physical examination must focus on identifying signs of impending septic shock and organ dysfunction.

Autonomic/Hemodynamic: Tachycardia and hypotension (SBP < 90 mmHg) are critical indicators of severity. These findings, when paired with the classic triad, constitute the transition to Reynolds' Pentad, signaling a high risk of mortality without immediate decompression ^[75]^B3b.
Mental Status: Septic encephalopathy manifests as confusion, lethargy, or a decreased ( < 15). This is a late finding and often indicates a failure of the blood-brain barrier due to systemic inflammatory mediators.
Abdominal Examination: RUQ tenderness is common, though peritoneal signs (guarding, rebound) are often absent unless gallbladder perforation or concomitant has occurred ^[73]^B3b.
Integumentary: is best visualized in the sclera or under the tongue when serum bilirubin exceeds 2–3 mg/dL.

Phenotypic Variants

Different etiologies of biliary obstruction present with distinct clinical nuances that can guide the initial differential diagnosis.

Variant	Key Features	Frequency
Primary Sclerosing Cholangitis (PSC)	Chronic fatigue, pruritus, and RUQ pain; often associated with Ulcerative Colitis ^[2]^B2b^[74]^D5.	17% have dominant strictures ^[80]^B2b.
IgG4-Related Cholangitis	Mimics biliary malignancy; often associated with ; dramatic response to corticosteroids ^[70]^B3b.	Rare; systemic fibroinflammatory ^[70]^B3b.
ICI-Induced Cholangitis	Occurs after immune checkpoint inhibitor therapy; presents with abdominal pain and fever ^[81]^B3b^[77]^B3b.	~12% of severe ICI-liver injuries ^[81]^B3b.
Post-PD Cholangitis	Late complication (median 14 months) after ; often due to reflux or anastomotic stricture ^[72]^B3b.	11% post- ^[72]^B3b.

Red Flags

Immediate escalation for biliary decompression is required if any of the following are present:

Hypotension (SBP < 90 mmHg) unresponsive to initial fluid resuscitation.
Altered Mental Status (confusion or disorientation).
High Fever (> 39°C) or hypothermia (< 36°C) suggesting severe sepsis.
Evidence of Organ Failure, such as oliguria or a need for vasopressors ^[76]^B2b.

Atypical Presentations

Clinicians must maintain a high index of suspicion in the elderly, who may present with "painless jaundice" or isolated mental status changes without fever. Similarly, patients on chronic immunosuppression or those with secondary sclerosing cholangitis due to (DILI) may lack a robust inflammatory response, masking the severity of the underlying infection ^[71]^B3b^[84]^D5.

Controversies and Guideline Disagreement

Question	Position A (Charcot's Triad)	Position B (TG18 Criteria)	Strength	Implication
Primary Diagnostic Tool	High specificity (98.7%) but very low sensitivity (15.8%) ^[75]^B3b.	Higher sensitivity by integrating labs and imaging ^[75]^B3b.	Strong (TG18 preferred)	Charcot's triad should never be used to rule out cholangitis.

Pearl: Charcot’s triad lacks the sensitivity (approx. 16–28%) required for screening, necessitating the use of the Tokyo Guidelines 2018 (TG18) which incorporate laboratory and imaging data to achieve higher diagnostic accuracy ^[75]^B3b.

Diagnostic Performance of Clinical Signs

Clinical Sign	Sensitivity	Specificity	PPV	NPV
Charcot's Triad (Complete)	15.8%	98.7%	50%	89%
Charcot's Triad (Incomplete)	28.6%	91.9%	36%	89%
TG18 Criteria	91.7%	77.7%	27%	99%

Data adapted from studies on ascending cholangitis ^[75]^B3b.

Tokyo Guidelines 2018 (TG18) Diagnostic Criteria

▸A definite TG18 diagnosis requires evidence of systemic inflammation, cholestasis, and biliary imaging findings (A+B+C).
▸A suspected diagnosis is established with systemic inflammation plus either cholestasis or imaging evidence (A + B or C).
▸Imaging is mandatory to upgrade a suspected diagnosis to a definite one, with MRCP being the most sensitive non-invasive modality.

Dx Diagnostic Essentials: The Tokyo Guidelines 2018 (TG18) are the global gold standard for diagnosis. A 'Definite' diagnosis requires all three pillars: Systemic Inflammation (Fever/CRP/WBC), Cholestasis (Jaundice/LFTs), and Imaging (Dilatation/Etiology).

HY High Yield: Charcot's Triad (fever, jaundice, RUQ pain) has a sensitivity of only 28.6% [75]. Never rule out acute cholangitis based on the absence of this triad; use TG18 criteria instead.

Integrating systemic inflammation, cholestasis, and imaging findings into a tripartite framework allows TG18 to achieve a diagnostic sensitivity exceeding 90% ^[88]^A1c^[90]^A1c. This structured approach was developed to address the limitations of the classic Charcot’s triad, which, while highly specific, fails to identify nearly 70% of patients with acute cholangitis in clinical practice ^[75]^B3b^[88]^A1c. The TG18 criteria categorize patients into "suspected" or "definite" diagnosis based on the presence of clinical and laboratory indicators across three distinct pillars ^[88]^A1c^[90]^A1c.

The Tripartite Framework

The TG18 diagnostic criteria are organized into three categories: Systemic Inflammation (A), Cholestasis (B), and Imaging Findings (C).

Pillar A: Systemic Inflammation: This requires either a documented fever (>38°C) or shaking chills, or laboratory evidence of an inflammatory response. Laboratory thresholds include a white blood cell (WBC) count <4,000 or >10,000/µL, or an elevated C-reactive protein (CRP) ≥1 mg/dL ^[88]^A1c^[90]^A1c.
Pillar B: Cholestasis: This is established by the presence of jaundice (serum total bilirubin ≥2 mg/dL) or abnormal liver function tests. Specifically, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) must be >1.5 times the upper limit of normal (ULN) ^[88]^A1c^[90]^A1c.
Pillar C: Imaging Findings: Diagnosis requires radiologic evidence of biliary dilatation or an identifiable etiology of obstruction, such as stones, strictures, or indwelling stents ^[98]^D5.

Diagnostic Algorithm and Thresholds

A suspected diagnosis is made if a patient meets one criterion in Pillar A and one criterion in either Pillar B or Pillar C. A definite diagnosis requires the presence of at least one criterion from all three pillars (A + B + C) ^[88]^A1c^[90]^A1c. This tiered approach ensures that patients with early or atypical presentations—such as those without overt jaundice but with clear imaging evidence of a stone—are still captured for urgent ^[95]^A1c.

In validation studies, the "gold standard" for confirming acute cholangitis includes the observation of purulent bile during drainage, rapid clinical remission following biliary decompression, or complete resolution of symptoms with targeted antimicrobial therapy ^[90]^A1c. While TG18 is the global standard, emerging neuro-symbolic AI models have demonstrated the potential to match or exceed human expert accuracy in applying these criteria, particularly in complex cases where laboratory findings are borderline ^[97]^C4.

Imaging Modalities in Diagnosis

Radiologists play a pivotal role in establishing the "definite" diagnosis by confirming Pillar C criteria ^[98]^D5. Transabdominal ultrasonography (US) is typically the first-line modality due to its availability, though it may miss small common bile duct (CBD) stones. Computed tomography (CT) is superior for identifying the level and cause of obstruction, such as pancreatic-biliary tumors or Mirizzi syndrome ^[98]^D5. Magnetic resonance cholangiopancreatography (MRCP) remains the most sensitive non-invasive test for and is essential when US and CT are inconclusive ^[98]^D5.

Special Considerations and Etiologies

The diagnostic workup must account for miscellaneous etiologies that may present with atypical features. Oriental cholangitis (recurrent pyogenic cholangitis), common in Southeast Asia, is characterized by intrahepatic and extrahepatic pigment stones and frequent strictures ^[87]^A1c. In liver transplant recipients, the threshold for suspicion must be lower, as these patients often lack classic systemic inflammatory signs due to immunosuppression; post-ERCP cholangitis in this cohort may occur despite single-dose antibiotic prophylaxis ^[25]^B3b. Furthermore, clinicians must distinguish standard acute cholangitis from acute suppurative cholangitis (ASC), a life-threatening variant characterized by pus under pressure in the biliary tree, which may require more aggressive intervention than non-suppurative forms ^[96]^B3b.

Controversies and Guideline Disagreement

Question	Position A (TG18)	Position B (Traditional)	Strength	Implication
Diagnostic Standard	Requires imaging for definite diagnosis ^[88]^A1c^[90]^A1c.	Relies on Charcot's Triad (Fever, Jaundice, RUQ pain) ^[75]^B3b.	High	TG18 increases sensitivity from ~28% to >90% ^[75]^B3b.
Inflammatory Markers	CRP ≥1 mg/dL is a core criterion ^[88]^A1c.	CRP is supportive but not diagnostic.	Moderate	TG18 allows diagnosis in afebrile patients with high CRP.

Pearl: TG18 criteria achieve a diagnostic sensitivity of approximately 91% by requiring only two of three clinical pillars for a "suspected" diagnosis, whereas the classic Charcot’s triad remains highly specific (92%) but clinically inadequate due to its poor sensitivity (28%) ^[75]^B3b^[88]^A1c.

TG18 Diagnostic Criteria for Acute Cholangitis

Category	Criteria	Thresholds
A. Systemic Inflammation	A-1. Fever and/or chills<br>A-2. Lab data	Fever >38°C<br>WBC <4k or >10k/µL; CRP ≥1 mg/dL
B. Cholestasis	B-1. Jaundice<br>B-2. Lab data	Total Bilirubin ≥2 mg/dL<br>ALP, GGT, AST, or ALT >1.5x ULN
C. Imaging	C-1. Biliary dilatation<br>C-2. Etiology	Evidence of stones, strictures, or stents on US, CT, or MRI

Severity Grading and Risk Stratification

▸TG18 Grade III is defined by new-onset dysfunction in any of six organ systems (cardiovascular, neurological, respiratory, renal, hepatic, or hematological).
▸Grade II (moderate) cholangitis is characterized by high-risk features such as age ≥75, bilirubin ≥5 mg/dL, or marked leukocytosis, and requires drainage within 48 hours.
▸Procalcitonin levels >3.0 ng/mL are highly predictive of Grade III severity and can assist in early triage when clinical signs of organ failure are subtle.

HY High Yield: In Grade III cholangitis, the most common organ dysfunctions are cardiovascular (hypotension) and renal (Cr >2.0). Always check a PT-INR and Platelet count, as hepatic and hematological failures are often the earliest silent markers of severe disease [99].

! Warning: Do not wait for the 'classic' Charcot's triad to grade severity; only 50-60% of patients with confirmed cholangitis present with all three symptoms, and its absence does not rule out Grade III disease [104].

Classification into three distinct severity tiers dictates the clinical trajectory of acute cholangitis, moving from elective to emergent life-saving intervention ^[99]^A1a^[103]^A1c. The Tokyo Guidelines 2018 (TG18) provide the global standard for this stratification, utilizing a framework that prioritizes the presence of organ dysfunction and specific markers of systemic inflammation ^[99]^A1a. This grading system is not merely descriptive; it is a prognostic tool where 30-day mortality increases significantly with each grade: 1.2% for Grade I, 2.6% for Grade II, and 8.4% for Grade III ^[105]^B3b.

Grade III: Severe Acute Cholangitis

Severe (Grade III) cholangitis is defined by the presence of at least one new-onset organ dysfunction ^[99]^A1a^[103]^A1c. This stage represents a critical failure of the body's compensatory mechanisms in response to biliary sepsis. The TG18 criteria identify six specific systems for assessment:

Cardiovascular: Hypotension requiring dopamine ≥5 μg/kg/min or any dose of norepinephrine ^[99]^A1a.
Neurological: Any disturbance in consciousness ^[99]^A1a.
Respiratory: A PaO2/FiO2 ratio < 300 ^[99]^A1a.
Renal: Serum creatinine > 2.0 mg/dL ^[99]^A1a.
Hepatic: PT-INR > 1.5 ^[99]^A1a.
Hematological: Platelet count < 100,000/mm³ ^[99]^A1a.

Patients meeting Grade III criteria require urgent biliary decompression and intensive care support, as the risk of rapid clinical decline is paramount ^[103]^A1c^[107]^B3b.

Grade II: Moderate Acute Cholangitis

Moderate (Grade II) cholangitis identifies patients who do not yet exhibit organ dysfunction but possess high-risk features that predict a failure to respond to initial medical therapy ^[99]^A1a. A diagnosis of Grade II requires the presence of at least two of the following five criteria:

Abnormal WBC count: >12,000/mm³ or <4,000/mm³ ^[99]^A1a.
High fever: Temperature ≥39°C (102.2°F) ^[99]^A1a.
Advanced age: ≥75 years ^[99]^A1a.
Hyperbilirubinemia: Total bilirubin ≥5 mg/dL ^[99]^A1a.
Hypoalbuminemia: Albumin <0.7 × lower limit of normal ^[99]^A1a.

These patients require early biliary decompression (typically within 24–48 hours) to prevent progression to organ failure ^[100]^B2b^[103]^A1c.

Grade I: Mild Acute Cholangitis

Grade I (mild) cholangitis is a diagnosis of exclusion, encompassing patients who meet the diagnostic criteria for acute cholangitis but do not fulfill the requirements for Grade II or III ^[99]^A1a^[103]^A1c. While these patients often respond to initial fluid resuscitation and antimicrobial therapy, the majority will still require biliary drainage during their index hospitalization to treat the underlying etiology and prevent recurrence ^[100]^B2b^[107]^B3b.

Biomarkers in Risk Stratification

Beyond the TG18 criteria, specific biomarkers offer enhanced granularity in predicting severity. Procalcitonin (PCT) has emerged as a superior predictor compared to white blood cell count or C-reactive protein (CRP) ^[101]^B2b. A PCT threshold of >2.2 ng/mL identifies patients with moderate-to-severe disease (Grade II/III) with high accuracy (AUC 0.81), while levels >3.0 ng/mL are highly specific for Grade III organ dysfunction (AUC 0.86) ^[101]^B2b. Additionally, the neutrophil-to-lymphocyte ratio (NLR) is an effective, low-cost tool for identifying patients at risk for severe presentations in resource-limited settings ^[7]^B3b.

Controversies and Guideline Disagreement

While TG18 provides a clear framework, the optimal timing for Grade II patients remains a subject of active debate, with some evidence suggesting that "early" drainage (48h) may still be too late for those at the higher end of the moderate spectrum ^[100]^B2b^[107]^B3b.

Question	Position A (TG18)	Position B (Recent Cohorts)	Strength	Implication
Timing for Grade II	Early drainage within 48 hours ^[103]^A1c.	Urgent drainage within 24 hours ^[100]^B2b^[107]^B3b.	Moderate	Earlier intervention may reduce length of stay and prevent progression to Grade III.
Predicting Drainage	Grading alone guides timing ^[99]^A1a.	Use of PCT/NLR to fast-track drainage ^[8]^B2b^[101]^B2b.	Emerging	Biomarkers may identify "Grade I" patients who will fail medical therapy.

Pearl: The presence of even a single organ dysfunction (Grade III) increases 30-day mortality seven-fold compared to mild cases, necessitating immediate biliary decompression regardless of the time of day ^[105]^B3b.

TG18 Severity Grading and Clinical Outcomes

Severity Grade	Definition	30-Day Mortality ^[105]^B3b	Recommended Drainage Timing ^[103]^A1c
Grade III (Severe)	Associated with at least one organ dysfunction	8.4%	Urgent (Immediately)
Grade II (Moderate)	≥2 of: WBC >12k/<4k, Fever ≥39°C, Age ≥75, Bili ≥5, Low Albumin	2.6%	Early (Within 24–48 hours)
Grade I (Mild)	Does not meet Grade II or III criteria	1.2%	Elective/Early (During index stay)

Laboratory and Radiologic Evaluation

▸Serum bilirubin >2 mg/dL and elevated inflammatory markers (WBC/CRP) are core diagnostic components of the TG18 criteria.
▸MRCP is the gold standard for non-invasive biliary mapping, though it may miss early cholangiocarcinoma in patients with primary sclerosing cholangitis.
▸IgG4-related sclerosing cholangitis is a critical mimic of malignancy; the IgG4-SC 2020 criteria offer 99% sensitivity for its identification.

Dx Diagnostic Essentials: Magnetic resonance cholangiopancreatography (MRCP) is the gold-standard non-invasive test for characterizing biliary anatomy and identifying the site of obstruction.

HY High Yield: In pediatric IBD patients, GGT is more sensitive than other liver enzymes for screening for primary sclerosing cholangitis; thresholds of 1–5× ULN should prompt MRCP.

! Warning: Normal initial laboratory tests do not exclude life-threatening cholangitis; pathogens like *Vibrio fluvialis* can cause rapid septic shock despite unremarkable baseline bloodwork.

Elevated inflammatory markers and cholestatic liver enzymes provide the biochemical foundation for a diagnosis under the Tokyo Guidelines 2018 (TG18) framework ^[98]^D5. While clinical suspicion often begins with Charcot's triad, definitive diagnosis and procedural planning rely on identifying the site and cause of biliary obstruction through cross-sectional imaging ^[98]^D5^[111]^B3b.

Laboratory Studies

Laboratory evaluation must be performed immediately to assess for systemic inflammation and cholestasis. Leukocytosis and elevated C-reactive protein (CRP) are common, though their absence does not exclude severe disease; for instance, Vibrio fluvialis cholangitis can present with unremarkable initial labs despite rapid progression to refractory septic shock ^[11]^C4^[114]^C4.

Cholestatic markers typically show significant elevation. Serum bilirubin >2 mg/dL is a key diagnostic threshold in the TG18 criteria ^[98]^D5. In pediatric populations with (IBD), gamma-glutamyltransferase (GGT) is a sensitive screening tool for underlying (PSC), with thresholds of 1×, 2×, or 5× the upper limit of normal (ULN) used to trigger further investigation ^[127]^B2b.

Specialized markers are required when autoimmune etiologies are suspected. Serum IgG4 levels are the hallmark of (IgG4-RD), though they may be normal preoperatively in some cases of IgG4-related sclerosing cholangitis (IgG4-SC) ^[112]^C4^[125]^D5. The IgG4-SC 2020 diagnostic criteria demonstrate a sensitivity of 99.0% when combining clinical, laboratory, and imaging findings ^[117]^B3b.

Radiologic Evaluation

Imaging is pivotal for confirming biliary dilation and identifying the obstructive etiology, such as , strictures, or neoplasms like intraductal papillary neoplasm of the bile duct (IPNB) ^[4]^D5^[98]^D5.

Transabdominal Ultrasound (US): Often the first-line modality due to its accessibility. It is highly specific for but has lower sensitivity for detecting distal common bile duct (CBD) stones or small biliary strictures ^[98]^D5^[122]^B3b.
Computed Tomography (CT): The emergency standard for identifying the level of obstruction and complications such as liver abscesses or pneumobilia ^[98]^D5^[114]^C4. CT is also useful for detecting immune-related adverse events (irAE) in patients on checkpoint inhibitors, which can manifest as simultaneous hepatitis, cholangitis, and pancreatitis ^[11]^C4.
Magnetic Resonance Cholangiopancreatography (MRCP): The non-invasive gold standard for mapping the biliary tree ^[129]^A1c. It is essential for diagnosing PSC, characterized by multifocal strictures and dilations ^[110]^B2a^[126]^A1c. However, MRCP has suboptimal performance for diagnosing early ductal (CCA) in the setting of PSC ^[130]^B3b.

Advanced and Emerging Modalities

Quantitative imaging techniques are increasingly used for risk stratification and fibrosis staging.

Elastography: Both magnetic resonance elastography (MRE) and transient elastography (FibroScan) estimate liver fibrosis. In children with choledochal malformations, a FibroScan score >6.7 kPa is associated with significant fibrosis ^[123]^B3b. In PSC, spatial heterogeneity in liver stiffness is common but does not necessarily predict clinical outcomes ^[119]^B3b.
Radiomics and Quantitative MRCP (MRCP+): These emerging tools offer objective metrics to reduce interpretation variability and improve the prediction of disease progression in chronic cholangiopathies ^[110]^B2a^[120]^B2b.
Sarcopenia Assessment: Imaging-derived biomarkers, such as psoas muscle thickness (PMT) at the L3 level, have shown prognostic value in patients with chronic biliary disease ^[121]^B3b.

Diagnostic Algorithm

Step 1: Elicit clinical signs (fever, jaundice, RUQ pain) and obtain immediate labs (WBC, CRP, LFTs) ^[98]^D5.
Step 2: Perform transabdominal ultrasound to screen for stones and ductal dilation ^[98]^D5.
Step 3: Proceed to contrast-enhanced CT or MRCP if US is inconclusive or if a malignant/complex obstruction is suspected ^[98]^D5^[129]^A1c.
Step 4: Apply TG18 criteria to establish diagnosis and severity grade ^[98]^D5.
Step 5: If ERCP is indicated but fails (5–7% of cases), consider endoscopic ultrasound-guided biliary drainage (EUS-BD) as an effective alternative ^[109]^A1a.

Controversies and Guideline Disagreement

Question	Position A	Position B	Strength	Implication
IgG4-SC vs. CCA	IgG4-SC can be diagnosed via IgG4-SC2020 criteria (99% sensitivity) ^[117]^B3b.	IgG4-SC frequently masquerades as CCA, often requiring histopathology for confirmation ^[112]^C4^[113]^C4.	Moderate	High risk of unnecessary surgery if misdiagnosed ^[113]^C4.
MRCP for CCA	MRCP is the preferred tool for biliary surveillance ^[129]^A1c.	MRCP has suboptimal sensitivity for ductal CCA in PSC patients ^[130]^B3b.	Weak	Negative MRCP does not fully exclude early malignancy ^[130]^B3b.

Pearl: MRCP remains the non-invasive gold standard for defining biliary anatomy, yet its sensitivity for detecting early cholangiocarcinoma in PSC remains limited, necessitating a multi-modal approach including clinical vigilance and potentially EUS-BD when ERCP fails ^[109]^A1a^[129]^A1c^[130]^B3b.

Comparative Utility of Imaging Modalities

Modality	Primary Utility	Limitations
Ultrasound	Initial screening; gallstone detection	Low sensitivity for distal CBD stones
CT Scan	Emergency evaluation; abscess detection	Radiation exposure; less detail for strictures
MRCP	Mapping strictures; PSC diagnosis	Suboptimal for early CCA; expensive
EUS	Alternative drainage (EUS-BD); stone detection	Invasive; requires specialized expertise

Initial Medical Management and Antimicrobial Therapy

▸Piperacillin-tazobactam is the preferred empiric agent for moderate-to-severe cholangitis due to its activity against Enterobacteriaceae, anaerobes, and Enterococci.
▸Blood culture-directed therapy is non-inferior to bile culture-directed therapy for mild-to-moderate cases once adequate biliary drainage is achieved.
▸Prophylactic antibiotics before ERCP reduce infectious complications (RR 0.54, 95% CI 0.29-0.98), though routine use remains debated in guidelines.

Rx Drug of Choice: Piperacillin-tazobactam 4.5 g IV every 6 hours is the first-line empiric choice for Grade II/III acute cholangitis, providing coverage for the most common biliary pathogens including E. coli, Klebsiella, and Enterococcus [131, 135].

! Warning: Ceftriaxone may induce biliary pseudolithiasis via calcium-salt precipitation, potentially mimicking or exacerbating biliary obstruction [29].

Immediate stabilization of acute cholangitis requires a dual-track approach: aggressive fluid resuscitation to mitigate sepsis-induced organ dysfunction and the rapid initiation of broad-spectrum antimicrobial therapy. While biliary decompression remains the definitive treatment, medical serves as the bridge to intervention, particularly in patients presenting with or .

Step 1: Sepsis Resuscitation and Stabilization

Initial management follows the Surviving Sepsis Campaign bundles, prioritizing the restoration of tissue perfusion. Administer 30 mL/kg of balanced crystalloid within the first 3 hours for patients with hypotension or lactate ≥4 mmol/L. In cases of refractory shock, vasopressor support (typically norepinephrine) is initiated to maintain a mean arterial pressure ≥65 mmHg. Clinicians must monitor for rapid progression; rare pathogens like Vibrio fluvialis can cause refractory septic shock and death within 12 hours of presentation, even with early ^[114]^C4 (4).

Step 2: Empiric Antimicrobial Selection

Antimicrobial therapy should be initiated within 1 hour of recognizing sepsis. Selection is guided by the Tokyo Guidelines 2018 (TG18) severity grading and local resistance patterns ^[91]^A1b^[137]^D5.

Grade I (Mild): Community-acquired cases typically respond to narrow-spectrum agents such as first- or second-generation cephalosporins or fluoroquinolones. However, use is associated with an increased risk of biliary pseudolithiasis due to calcium-salt precipitation, which may complicate the clinical course ^[29]^B3b (3b).
Grade II/III (Moderate to Severe): These require broad-spectrum coverage against Gram-negative Enterobacteriaceae (E. coli, Klebsiella spp.) and anaerobes. 4.5 g IV every 6 hours is a standard first-line choice due to its excellent biliary penetration and anaerobic activity ^[32]^B2a (2a).
Enterococcal Coverage: Enterococcus species are frequently isolated from bile cultures (up to 35-40% in some series) ^[135]^B3b (3b). Coverage is specifically recommended for Grade III (severe) cases, healthcare-associated infections, or in patients with prior biliary-enteric anastomoses ^[135]^B3b^[145]^B2b.

Step 3: Microbiological Tailoring and Source Control

Blood cultures are positive in approximately 20-30% of cases. While bile cultures often yield a broader spectrum of organisms, a randomized non-inferiority trial (N=222) demonstrated that adjusting antibiotics based on blood cultures alone is non-inferior to using both blood and bile cultures in mild-to-moderate cholangitis after successful drainage ^[131]^A1b (1b). The primary outcome of organ failure occurred at similar rates between groups (RR 1.02, 95% CI 0.88–1.18) ^[131]^A1b.

Step 4: Duration of Therapy

TG18 traditionally recommends 4 to 7 days of therapy after successful biliary decompression ^[91]^A1b^[137]^D5. However, emerging evidence suggests shorter courses may be sufficient. Retrospective data indicate that therapy ≤4 days does not increase mortality or readmission rates compared to longer courses (p=0.45) ^[139]^B3b (3b). The ongoing COBRA and BOLT-P3 trials are currently evaluating whether 1 day of post-drainage antibiotics is non-inferior to standard 4-7 day regimens ^[91]^A1b^[137]^D5.

Step 5: Management of Recurrent and Special Populations

For patients with recurrent non-obstructive cholangitis (RNOC) after or hepaticojejunostomy, a "step-up" approach is utilized ^[134]^C4^[144]^B3b. Selective decontamination of the digestive tract (SDD) using oral non-absorbable antibiotics (colistin, tobramycin, nystatin) has been shown to reduce the incidence density of cholangitis from 1.05 to 0.37 per 100 patient days (RR 0.35, 95% CI 0.21–0.59) ^[146]^C4 (4). In patients with (PSC), oral is being investigated for its immunomodulatory effects and potential to improve liver biochemistry ^[18]^D5^[133]^B2a^[147]^B3b.

Controversies and Guideline Disagreement

Question	Position A	Position B	Strength	Implication
Routine ERCP Prophylaxis	TG18/Guidelines — Recommend prophylaxis only for anticipated incomplete drainage or immunosuppression ^[138]^A1a.	Meta-analysis (2026) — Prophylactic antibiotics reduce infectious complications in all suspected biliary obstructions (RR 0.54, 95% CI 0.29–0.98) ^[132]^A1a.	Moderate	Routine use may reduce post-ERCP cholangitis but risks increasing antimicrobial resistance ^[132]^A1a^[143]^B3b.
Antibiotic Duration	Standard Practice — 4–7 days post-drainage based on expert consensus ^[91]^A1b.	Emerging Evidence — 1–3 days may be sufficient for mild-to-moderate cases with successful source control ^[137]^D5^[139]^B3b.	Moderate	Shorter courses reduce hospital stay and antibiotic exposure without compromising safety ^[91]^A1b^[131]^A1b.

Pearl: Initiate broad-spectrum antibiotics within 60 minutes of sepsis recognition; while 4-7 days is the current standard, therapy may be tailored to as little as 24-48 hours following definitive biliary decompression in uncomplicated cases ^[91]^A1b^[131]^A1b^[139]^B3b.

Empiric Antimicrobial Regimens by Severity

Severity (TG18)	Recommended Regimen	Rationale	Evidence Level
Grade I (Mild)	Ceftriaxone (2g IV q24h) + Metronidazole (500mg IV q8h)	Covers common Gram-negatives and anaerobes; community-acquired.	2a ^[32]^B2a^[137]^D5
Grade II (Moderate)	Piperacillin-tazobactam (4.5g IV q6h)	Broad spectrum including Enterococcus and Pseudomonas.	1b ^[131]^A1b^[135]^B3b
Grade III (Severe)	Meropenem (1g IV q8h)	Escalation for septic shock or suspected MDR organisms.	5 ^[91]^A1b
Healthcare-Assoc.	Vancomycin (15-20mg/kg IV q12h) + Cefepime (2g IV q8h)	High risk for MRSA and resistant Gram-negatives.	3b ^[145]^B2b

Dosing and Adjustments for Biliary Antimicrobials

Drug	Starting Dose	Target / Max Dose	Renal Adjustment	Hepatic Adjustment	Key Monitoring
Piperacillin-tazobactam	4.5 g IV q6h	18 g/day	CrCl <20: 2.25 g q6h	No adjustment	Cr, CBC, LFTs
Ceftriaxone	2 g IV q24h	4 g/day	No adjustment	No adjustment	Biliary sludge/stones ^[29]^B3b
Metronidazole	500 mg IV q8h	1500 mg/day	No adjustment	Reduce dose in severe failure	Neuropathy
Vancomycin (Oral)	125 mg PO QID	500 mg QID	No adjustment	No adjustment	Trough (if systemic) ^[18]^D5

Biliary Decompression: Timing and Modalities

▸Urgent ERCP within 24 hours reduces 30-day mortality in mild-to-moderate acute cholangitis (NNT = 9).
▸In patients with sepsis-induced coagulopathy, biliary drainage without sphincterotomy is preferred to minimize bleeding risks.
▸EUS-guided biliary drainage is a highly effective salvage modality when ERCP fails, offering comparable success to percutaneous approaches.

HY High Yield: In severe acute cholangitis (Grade III), the goal for decompression is <12 hours. For Grade I/II, the goal is <24 hours to optimize survival outcomes [148, 151].

! Warning: Endoscopic sphincterotomy (EST) should be avoided in patients with sepsis-induced coagulopathy (SIC) as it significantly increases bleeding risk without improving clinical outcomes [37].

Decompression of the biliary tree within 24 hours of presentation significantly reduces 30-day mortality in patients with acute cholangitis ^[148]^A1b^[157]^B3b. While initial medical stabilization with fluids and is mandatory, the definitive resolution of the septic focus requires mechanical relief of the obstruction. The choice between endoscopic, percutaneous, or surgical modalities depends on the patient's clinical stability, the underlying etiology, and the availability of local expertise ^[17]^A1b^[109]^A1a^[158]^C4.

Timing of Intervention

The urgency of biliary decompression is dictated by the severity of the clinical presentation and the response to initial medical therapy. For patients with severe (Grade III) acute cholangitis, emergent decompression within 12 hours is often necessary to prevent irreversible organ failure ^[151]^C4^[161]^B2c. In mild-to-moderate (Grade I and II) cases, urgent ERCP performed within 24 hours is superior to early ERCP (24–48 hours), reducing 30-day mortality from 19% to 8% (ARR 11%; NNT = 9) ^[148]^A1b. Delays beyond 48 hours are associated with increased hospital length of stay and higher rates of persistent organ failure ^[148]^A1b^[157]^B3b.

Endoscopic Retrograde Cholangiopancreatography (ERCP)

ERCP remains the gold standard for biliary decompression due to its high technical success rate and the ability to treat the underlying cause, such as stone extraction ^[17]^A1b^[157]^B3b. In critically ill patients in the intensive care unit (ICU), "BEDSIDE" ERCP without fluoroscopy has been described as a feasible salvage technique when conventional transport is impossible ^[151]^C4.

Sphincterotomy vs. Stenting: While endoscopic sphincterotomy (EST) facilitates stone removal, it may increase bleeding risk in patients with sepsis-induced coagulopathy (SIC) ^[37]^B3b. In the setting of SIC, biliary drainage alone (via plastic stent or nasobiliary tube) is preferred, as EST increases bleeding without providing additional clinical benefit ^[37]^B3b^[160]^B2b.
Special Populations: ERCP is safe and effective in the longevous population (aged ≥90 years), with success rates comparable to younger cohorts ^[155]^B3b. However, patients with advanced chronic kidney disease (CKD stages 4–5) or end-stage renal disease (ESRD) face higher odds of post-procedural bleeding and ICU admission ^[156]^B3b. Liver transplant recipients with anastomotic strictures also require careful , as they are at higher risk for post-ERCP cholangitis ^[25]^B3b^[33]^B3b.

Alternative Decompression Modalities

When ERCP is technically unfeasible or fails (occurring in 5%–7% of cases), alternative routes must be pursued ^[109]^A1a.

Percutaneous Transhepatic Biliary Drainage (PTBD): In severe acute cholangitis caused by common bile duct stones, ERCP is superior to PTBD, with lower mortality (6.3% vs. 19%; ARR 12.7%; NNT = 8) and fewer complications ^[17]^A1b. PTBD is typically reserved for patients with altered anatomy (e.g., Roux-en-Y) or failed endoscopic access ^[17]^A1b.
EUS-Guided Biliary Drainage (EUS-BD): EUS-BD has emerged as a highly effective salvage technique after failed ERCP, offering comparable clinical success to PTBD but with potentially fewer adverse events ^[109]^A1a^[149]^A1a. In malignant distal biliary obstruction, EUS-BD and ERCP show similar technical (RR 1.01) and clinical (RR 1.10) success rates ^[149]^A1a.
Laparoscopic Common Bile Duct Exploration (LCBDE): LCBDE is a safe alternative to the two-stage approach (ERCP followed by ) for difficult common bile duct stones, potentially reducing the overall length of stay ^[158]^C4^[162]^B3b.

Peri-procedural Antibiotic Management

Prophylactic antibiotics reduce infectious complications after ERCP in patients with suspected biliary obstruction ^[132]^A1a^[138]^A1a. While guidelines traditionally recommend prophylaxis only for anticipated incomplete drainage, recent meta-analyses suggest a broader benefit in reducing post-procedural cholangitis and bacteremia ^[132]^A1a^[138]^A1a^[143]^B3b.

Following successful decompression, the optimal duration of antibiotic therapy remains a subject of active investigation. While the Tokyo Guidelines 2018 (TG18) recommend 4–7 days, emerging evidence from the COBRA and BOLT-P3 trials suggests that a shorter course (1–3 days) may be non-inferior in patients who achieve adequate drainage ^[91]^A1b^[137]^D5^[139]^B3b.

Controversies and Guideline Disagreement

Question	Position A	Position B	Strength	Implication
Timing in Grade I/II	Urgent (<24h) reduces mortality ^[148]^A1b^[157]^B3b.	Early (24–48h) is sufficient if stable [TG18].	Moderate	Shift toward earlier intervention regardless of grade.
EST in Sepsis	Avoid EST to minimize bleeding risk ^[37]^B3b.	EST prevents post-ERCP pancreatitis ^[160]^B2b.	Low	Drainage-only is safer in coagulopathy.
Antibiotic Duration	Standard 4–7 days [TG18].	Short-course (1–3 days) is sufficient ^[91]^A1b^[139]^B3b.	Emerging	Potential for reduced antibiotic resistance.

Pearl: Urgent biliary decompression within 24 hours is the most critical intervention for reducing mortality in acute cholangitis, with ERCP being the preferred modality over PTBD (NNT = 8 for mortality benefit in severe cases) ^[17]^A1b^[148]^A1b.

Comparison of Decompression Modalities

Modality	Primary Indication	Key Advantage	Major Limitation
ERCP	First-line for most cases	Therapeutic (stone removal)	Failed access in 5-7% ^[109]^A1a
PTBD	Failed ERCP / Altered anatomy	High success in proximal blocks	Higher mortality in severe AC ^[17]^A1b
EUS-BD	Salvage after failed ERCP	Internal drainage; high success ^[109]^A1a	Requires advanced expertise
LCBDE	Concomitant cholelithiasis	Single-stage treatment ^[158]^C4	Technically demanding

Alternative Decompression: PTBD and Surgical Intervention

▸PTBD is the primary salvage modality when ERCP fails or is contraindicated, showing similar efficacy to ERCP in severe acute cholangitis from CBD stones.
▸Percutaneous drainage is superior to endoscopic drainage for perihilar cholangiocarcinoma due to a significantly lower risk of procedure-related pancreatitis (OR 8.47).
▸Emergency surgery is now a last-resort intervention, indicated only when both endoscopic and percutaneous decompression fail or for specific etiologies like Caroli's syndrome.

! Warning: Immediate post-procedural cholangitis occurs in over 25% of patients following PTBD; close hemodynamic monitoring and continued antimicrobial therapy are essential in the first 24 hours [177].

HY High Yield: In patients with Bismuth III or IV perihilar cholangiocarcinoma, PTBD is often the preferred initial drainage method over ERCP to minimize the risk of contaminated, undrained segments and procedure-related pancreatitis [165, 167].

Percutaneous transhepatic biliary drainage (PTBD) serves as the primary salvage therapy when endoscopic retrograde cholangiopancreatography (ERCP) is technically unfeasible or fails to achieve adequate decompression ^[163]^C4^[170]^A1c. While ERCP remains the first-line modality due to its less invasive nature, PTBD provides a critical alternative for patients with altered surgical anatomy, such as those with post-living donor liver transplant biliary complications or Roux-en-Y reconstructions ^[163]^C4^[169]^C4. In severe acute cholangitis (Grade III) caused by common bile duct stones, PTBD demonstrates comparable effectiveness and safety to ERCP, making it a robust option in the emergency setting ^[17]^A1b.

PTBD in Malignant and Complex Obstruction

For perihilar cholangiocarcinoma (Klatskin tumors), PTBD often outperforms endoscopic drainage in technical success and complication profiles ^[164]^A1a^[166]^B2a. Meta-analyses indicate that PTBD is associated with a significantly lower risk of procedure-related pancreatitis (OR 8.47, 95% CI 2.28-31.45; NNT not calculable from reported data) and overall drainage-related complications compared to endoscopic methods (OR 2.73, 95% CI 1.52-4.91) ^[167]^B2a. This advantage is particularly pronounced in preoperative settings where maintaining a sterile biliary tree is paramount to reducing postoperative morbidity ^[165]^B2a^[181]^B3b.

Technical Considerations and Bedside Intervention

In critically ill patients who are too hemodynamically unstable for transport to a fluoroscopy suite, bedside ultrasound-guided PTBD offers a feasible life-saving intervention ^[173]^B3b^[174]^C4. Technical success in these ICU settings is high, though clinicians must monitor for immediate post-procedural cholangitis, which occurs in approximately 25.9% of patients within 24 hours of the intervention ^[177]^B3b. Long-term PTBD may be complicated by intestinal reflux through the catheter, particularly in patients with bilioenteric anastomoses, sometimes requiring modified antireflux catheters to prevent recurrent obstruction ^[175]^C4.

Surgical Intervention as a Last Resort

Emergency surgery has largely transitioned from a primary treatment to a "last resort" modality for acute cholangitis ^[170]^A1c^[172]^D5. Indications for surgical decompression include failed endoscopic and percutaneous attempts, or specific underlying pathologies such as where cystic dilatations may require resection or Roux-en-Y hepaticojejunostomy ^[171]^D5. In rare cases of significant following PTBD (occurring in <5% of cases), surgery is indicated if hepatic artery embolization fails to control the hemorrhage ^[168]^C4. Robotic-assisted biliary stricturoplasty or hepaticojejunostomy may also be required for complex strictures, such as those resulting from hepatic artery infusion pump (HAIP) injury ^[169]^C4.

Controversies and Guideline Disagreement

Question	Position A	Position B	Strength	Implication
Best initial drainage for perihilar cholangiocarcinoma?	EBD (Endoscopic): Preferred by some for lower seeding risk and patient comfort ^[164]^A1a.	PTBD (Percutaneous): Preferred for higher technical success and lower pancreatitis rates ^[167]^B2a^[181]^B3b.	Moderate	PTBD is increasingly favored for complex hilar (Bismuth III/IV) cases ^[165]^B2a.

Pearl: PTBD is the preferred alternative to ERCP in complex hilar obstructions due to lower pancreatitis rates (OR 8.47) and higher technical success, while surgery remains reserved for refractory cases or specific anatomical anomalies ^[167]^B2a^[168]^C4^[170]^A1c.

Complications of Percutaneous Transhepatic Biliary Drainage (PTBD)

Complication	Incidence/Risk	Clinical Action
Immediate Post-procedural Cholangitis	~25.9% ^[177]^B3b	Monitor for fever within 24 hours; ensure antibiotic coverage.
Clinically Significant Hemobilia	<5% ^[168]^C4	Requires hepatic artery embolization or, rarely, surgery.
Catheter Obstruction/Reflux	Variable ^[175]^C4	Consider antireflux catheters in patients with bilioenteric anastomosis.
Technical Failure (Stone Removal)	~17% ^[179]^B3b	May require basket lithotripsy or surgical exploration.
Procedure-related Pancreatitis	Low (vs EBD) ^[167]^B2a	Significantly lower risk than ERCP (OR 0.12).

Management of Underlying Etiologies

▸Laparoscopic common bile duct exploration with primary closure is a safe one-stage treatment for mild-to-moderate calculous acute cholangitis.
▸Primary sclerosing cholangitis requires lifelong surveillance for gallbladder cancer and HCC, with liver transplantation reserved for end-stage disease.
▸IgG4-related cholangitis typically responds to steroids, but mechanical decompression may be a viable alternative in obstruction-dominant cases.

HY High Yield: In patients with PSC, the presence of gallbladder polyps carries a 16.4% risk of being a mass lesion, necessitating a low threshold for cholecystectomy [182].

! Warning: MELD scores often underestimate the mortality risk in PSC patients due to recurrent cholangitis, leading to 'MELD purgatory' on transplant waitlists [186].

Definitive of the underlying biliary pathology is essential to prevent recurrent sepsis and long-term ductal injury. While initial stabilization focuses on decompression and antimicrobial therapy, the transition to curative or long-term suppressive strategies depends on the specific obstructive etiology.

Calculous Disease and Surgical Timing

Laparoscopic common bile duct exploration (LCBDE) is a safe and effective alternative to the traditional two-stage approach (ERCP followed by ) for patients with acute cholangitis (AC) caused by ^[183]^B2a. In cases of mild-to-moderate calculus-associated AC, LCBDE with primary duct closure (PDC)—omitting a T-tube—demonstrates comparable safety to non-AC cohorts, provided the duct is sufficiently dilated and cleared ^[184]^B3b. For patients presenting with biliary pancreatitis and AC, same-admission cholecystectomy is the standard of care, as it significantly reduces the risk of relapse and lowers overall healthcare costs compared to interval surgery ^[187]^D5. In complex cases where mechanical lithotripsy leads to basket impaction, salvage techniques such as peroral cholangioscopy-guided electrohydraulic lithotripsy (EHL) may prevent the need for emergency open surgery ^[153]^C4.

Malignant Biliary Obstruction

Management of malignant obstructions often requires a transition from temporary drainage to permanent stenting. Percutaneous transhepatic bile duct stent insertion serves as a critical salvage modality when endoscopic access to the papilla of Vater is technically unfeasible ^[189]^B3b. For complete biliary obstructions where conventional guidewire passage fails, magnetic compression anastomosis (MCA) has emerged as a minimally invasive option to re-establish ductal continuity, though it requires specialized equipment and expertise ^[20]^B2a. In patients with massive (HCC) causing biliary symptoms, quadruple conversion therapies—combining immune checkpoint inhibitors (e.g., ), tyrosine kinase inhibitors (e.g., 8–12 mg daily), and locoregional treatments—may downstage unresectable tumors to allow for curative resection ^[190]^C4.

Primary Sclerosing Cholangitis (PSC)

PSC management focuses on treating dominant strictures and monitoring for hepatobiliary malignancies. While MRCP is the primary diagnostic tool, ERCP remains indispensable for tissue sampling to differentiate PSC from ^[50]^D5. Patients with PSC and concomitant (PSC-IBD) represent a high-risk phenotype requiring annual colonoscopic surveillance due to an elevated risk of colorectal neoplasia ^[185]^D5^[192]^D5. (LT) is the only curative option for end-stage PSC, accounting for 8%–14% of LT procedures in North America ^[186]^D5. Post-transplant outcomes are generally excellent, though disease recurrence affects 15%–35% of patients within 5–10 years ^[186]^D5.

IgG4-Related and Rare Etiologies

IgG4-related cholangitis (IRC) is distinguished by its dramatic response to systemic corticosteroids, which remains the first-line therapy ^[70]^B3b. However, some patients present with an "obstruction-dominant" phenotype that may achieve remission through intensive endoscopic mechanical decompression alone, potentially sparing long-term steroid exposure ^[152]^C4. Rare causes, such as secondary choledocholithiasis triggered by foreign bodies (e.g., fish bones), require complete removal of the nidus to prevent stone recurrence ^[193]^C4.

Controversies and Guideline Disagreement

Question	Position A	Position B	Strength	Implication
LCBDE in AC	Safe and effective for definitive one-stage management ^[183]^B2a^[184]^B3b.	Prefer ERCP followed by elective cholecystectomy to minimize surgical risk during acute infection.	Moderate	LCBDE is increasingly utilized in centers with advanced laparoscopic expertise.
Antibiotic Duration	Standard 4–7 days post-decompression (TG18) ^[188]^D5.	Short course (1–3 days) may be sufficient for uncomplicated calculous AC ^[188]^D5.	Emerging	Shorter courses may reduce resistance and antibiotic-associated adverse events.

Pearl: Definitive management must target the specific obstructive trigger—ranging from same-admission cholecystectomy for stones to multidisciplinary surveillance for PSC—to mitigate the high risk of recurrent sepsis and malignancy ^[186]^D5^[187]^D5.

Etiology-Specific Management Strategies

Etiology	Primary Management Strategy	Key Consideration
Choledocholithiasis	ERCP or LCBDE + Cholecystectomy	Same-admission surgery prevents recurrence ^[187]^D5.
Malignant Stricture	Endoscopic or Percutaneous Stenting ^[189]^B3b	MCA for complete obstructions ^[20]^B2a.
PSC	Endoscopic dilation + Surveillance	High risk of CCA and HCC (especially if cirrhotic) ^[31]^B2b^[50]^D5.
IgG4-SC	Systemic Corticosteroids ^[70]^B3b	Mimics malignancy; requires IgG4 serology/biopsy.
Foreign Body	Endoscopic removal ^[193]^C4	Acts as a nidus for recurrent stone formation.

Complications and Long-term Outcomes

▸RDW is a significant independent predictor of 30-day mortality in critically ill patients with acute cholangitis [198].
▸Concomitant PSC and IBD increases the risk of mortality and surgery by 56% compared to IBD alone [196].
▸Short-course antibiotic therapy (≤4 days) after successful ERCP is non-inferior to traditional 7-day regimens in preventing recurrence [139].

HY High Yield: In patients with PSC, the presence of IBD is not merely a comorbidity but a major prognostic driver, increasing the hazard for major clinical events by over 50% [196].

! Warning: Enterococcal-positive bile cultures are associated with increased risk of treatment failure; consider adding vancomycin or linezolid in patients not responding to standard cephalosporin/metronidazole therapy [135].

Mortality in critically ill patients with acute cholangitis is frequently driven by the progression of systemic inflammatory response syndrome (SIRS) to multi-organ dysfunction syndrome (MODS). While 30-day mortality in mild-to-moderate cases is relatively low and does not significantly differ between urgent (<24 hours) and early (24–48 hours) endoscopic retrograde cholangiopancreatography (ERCP) ^[148]^A1b, severe cases (Grade III) carry a substantial risk of death. Red cell distribution width (RDW) has emerged as a robust independent predictor of 30-day mortality in critically ill patients, reflecting the severity of the underlying inflammatory stress and physiological reserve ^[198]^B3b.

Respiratory and Autonomic Monitoring

Critical care focuses on the early identification of septic shock and acute respiratory distress syndrome (ARDS). Unlike neuromuscular disorders, respiratory failure in acute cholangitis is typically a consequence of capillary leak and pulmonary edema rather than ventilatory pump failure. Monitoring focuses on the PaO2/FiO2 ratio, with a threshold of <300 indicating significant lung injury requiring positive pressure ventilation. Autonomic instability manifests as refractory hypotension and tachyarrhythmias; patients requiring vasopressor support (e.g., norepinephrine) must be monitored for secondary ileus and mesenteric ischemia, which can complicate the post-procedural course.

Systemic and Local Sequelae

Acute kidney injury (AKI) occurs in approximately 15–25% of severe cases due to a combination of pigment nephropathy from hyperbilirubinemia and sepsis-induced hypoperfusion. Local complications include the formation of pyogenic liver abscesses, which may develop if biliary decompression is delayed or incomplete. The presence of enterococci in bile cultures is a specific concern, as it is associated with higher rates of bactobilia and may necessitate broader empirical coverage to prevent short-term recurrence ^[135]^B3b. In patients with underlying primary sclerosing cholangitis (PSC), the risk of developing cholangiocarcinoma remains a lifelong threat, with 1-year mortality significantly higher in those with concomitant periampullary malignancies ^[111]^B3b^[194]^B3b.

Long-term Survival and Recurrence

Recurrent biliary events are common, particularly in patients with primary sclerosing cholangitis (PSC) and concomitant inflammatory bowel disease (IBD). Patients with both PSC and IBD face a significantly worse prognosis, with a 1.56-fold increased risk (HR 1.56, 95% CI 1.41-1.72) of a composite endpoint including mortality, hospitalization, and surgery compared to those with IBD alone ^[196]^B3b. For those requiring (LT), 5-year survival rates are approximately 85–88% ^[194]^B3b^[199]^B2a. Post-transplant outcomes are influenced by the type of biliary reconstruction; duct-to-duct anastomosis and Roux-en-Y hepaticojejunostomy show comparable graft survival, though biliary complications remain a frequent cause of late morbidity ^[21]^B2a.

Controversies and Guideline Disagreement

Question	Position A	Position B	Strength	Implication
Antibiotic Duration	4–7 days post-drainage (TG18) ^[91]^A1b	≤4 days (Short-course) ^[139]^B3b	Moderate	Shorter courses may reduce resistance without increasing recurrence.
ERCP Timing	Urgent (<24h) for all ^[148]^A1b	Early (24–48h) for mild/mod ^[148]^A1b	High	Timing in non-severe cases may be flexible if stable.

Pearl: Red cell distribution width (RDW) is a potent predictor of 30-day mortality in severe cholangitis ^[198]^B3b, and while TG18 recommends 4–7 days of , successful biliary decompression may allow for a shortened course of ≤4 days without compromising outcomes ^[139]^B3b.

Common Complications of Acute Cholangitis

Complication	Frequency	Prevention	Management
Sepsis/Septic Shock	10–30%	Early antibiotics & drainage	Vasopressors, fluid resuscitation
Acute Kidney Injury	15–25%	Maintain MAP >65 mmHg	Hydration, avoid nephrotoxins
Liver Abscess	5–10%	Complete decompression	Percutaneous drainage, extended antibiotics
Post-ERCP Pancreatitis	3–10%	Rectal indomethacin, hydration	Bowel rest, aggressive IV fluids
Recurrent Cholangitis	10–20%	Definitive stone/stricture tx	Repeat ERCP, long-term stenting

Landmark Evidence and Guideline Evolution

▸The transition from TG07 to TG13/18 significantly improved diagnostic sensitivity by incorporating a gold standard based on clinical response to drainage.
▸TG13 introduced management bundles that mandate urgent biliary decompression within 24 hours for severe (Grade III) cases.
▸ESGE 2019 guidelines advocate for stone extraction in all fit patients with common bile duct stones, even if asymptomatic, to prevent future episodes of cholangitis.

HY High Yield: The TG13/18 'gold standard' for a definite diagnosis of acute cholangitis is the presence of purulent bile during drainage or rapid clinical remission following biliary decompression [90].

Standardization of began with the 2007 Tokyo Guidelines (TG07), which provided the first international consensus on diagnostic criteria and severity grading ^[92]^A1c^[94]^A1c. Before this, clinicians relied on Charcot’s triad, which suffered from poor sensitivity (approximately 26%) ^[94]^A1c. TG07 introduced a framework based on systemic inflammation, cholestasis, and imaging findings, though subsequent validation revealed significant limitations in diagnostic sensitivity and a disconnect between severity grading and clinical outcomes ^[203]^A1c^[88]^A1c.

Evolution of the Tokyo Guidelines (TG07 to TG18)

The 2013 update (TG13) addressed these gaps by refining the diagnostic criteria to include a definite diagnosis category, validated against a gold standard of purulent bile or rapid clinical remission following biliary decompression ^[90]^A1c. TG13 also introduced management bundles—structured sets of evidence-based practices that, when implemented together, improve patient prognosis ^[205]^A1c. These bundles emphasize the timing of biliary drainage: urgent (within 24 hours) for Grade III (severe) cases and early (within 24–48 hours) for Grade II (moderate) cases ^[202]^A1c^[204]^A1c. The TG18 revision further refined these bundles, maintaining the core severity grading while optimizing the diagnostic sensitivity for community-acquired versus healthcare-associated infections ^[206]^A1c.

ESGE 2019 and Diagnostic Pathways

The European Society of Endoscopy (ESGE) 2019 guidelines further refined the diagnostic algorithm, recommending a combination of liver function tests and abdominal ultrasonography as the initial step ^[201]^A1c. For patients with persistent suspicion but negative ultrasound, ESGE strongly recommends (EUS) or (MRCP) ^[201]^A1c. Crucially, ESGE recommends stone extraction for all patients with common bile duct stones, regardless of symptoms, provided they are fit for the procedure ^[201]^A1c.

Controversies and Guideline Disagreement

While TG13/18 and ESGE largely align, subtle differences exist regarding the timing of intervention in mild (Grade I) cases and the role of percutaneous transhepatic biliary drainage (PTBD).

Question	Position A (TG13/18)	Position B (ESGE)	Strength	Implication
Timing for Grade I	Medical therapy first; drainage if no response ^[202]^A1c	Offer stone extraction to all fit patients ^[201]^A1c	Moderate	ESGE favors earlier definitive stone clearance.
Drainage Modality	ERCP is first choice; PTBD for failures ^[204]^A1c	ERCP preferred; EUS-guided drainage as alternative ^[201]^A1c	Strong	Increasing role for EUS-guided techniques over PTBD.

Clinical Prediction Tools and Patient Resources

Clinicians utilize the Tokyo Guidelines 2018 Severity Grading Calculator to determine the urgency of intervention. For patients, resources such as the ASGE Patient Information Portal and the NIDDK Biliary Tract Disorders page provide essential education on the risks of and the necessity of .

Pearl: The evolution from TG07 to TG18 has shifted the focus from simple clinical triads to a multi-modal diagnostic approach, where the gold standard for diagnosis remains the observation of purulent bile or clinical remission following decompression ^[90]^A1c^[203]^A1c. Implementation of TG13/18 management bundles is essential to reduce mortality, particularly in Grade II and III disease ^[202]^A1c^[205]^A1c.

Comparison of Major Clinical Guidelines

Guideline	Organization	Year	Key Recommendations
TG07	International Consensus	2007	First standardized diagnostic criteria and SIRS-based severity grading ^[92]^A1c^[94]^A1c.
TG13	Tokyo Revision Committee	2013	Introduced management bundles and refined diagnostic sensitivity based on multicenter analysis ^[203]^A1c^[205]^A1c.
ESGE	European Society of GI Endoscopy	2019	Recommended EUS/MRCP for intermediate risk and stone extraction for all fit patients ^[201]^A1c.

References

[1]
Trauner M, Levy C, Tanaka A et al.. “Cilofexor in non-cirrhotic primary sclerosing cholangitis (PRIMIS): a randomised, double-blind, multicentre, placebo-controlled, phase 3 trial.” The lancet. Gastroenterology & hepatology (2026). PMID: 41173015 ↗
L1RCTCited in: Definition, Classification, and Historical Context
[2]
Theodoros V, Fotios F, Konstantinos M et al.. “HERACLIS-PSC: Current characteristics of primary sclerosing cholangitis with or without inflammatory bowel disease in Greece-a national multicenter cohort study.” Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (2026). PMID: 41577581 ↗
L2COHORTCited in: Definition, Classification, and Historical Context, Epidemiology and Risk Factors, Clinical Presentation and Physical Examination
[3]
Mammadov RA, Roest HP, van der Laan LJ et al.. “Dietary and Lifestyle Risk Factors in Primary Sclerosing Cholangitis: In Search of Mechanistic Explanations and Health Improvement.” The Journal of nutrition (2025). PMID: 41176278 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification, and Historical Context
[4]
Aziz H, Seda P, Gosse M et al.. “Intraductal papillary neoplasm of the bile duct.” HPB : the official journal of the International Hepato Pancreato Biliary Association (2025). PMID: 41006119 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification, and Historical Context, Laboratory and Radiologic Evaluation
[5]
Curto A, Cristoferi L, Carbone M et al.. “Primary sclerosing cholangitis: what is new in the therapeutic landscape.” Current opinion in immunology (2025). PMID: 40683116 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification, and Historical Context
[6]
Naitoh I, Yoshida M, Nakazawa T. “Endoscopic diagnosis of immunoglobulin G4-related sclerosing cholangitis.” Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society (2025). PMID: 40256978 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification, and Historical Context, Laboratory and Radiologic Evaluation
[7]
Angelescu C, Cozma MA, Mateescu RB et al.. “Comparison of NLR and CRP in Identifying Organ Dysfunction-Based Severe Presentation of Acute Cholangitis in Patients with Choledocholithiasis: A Single-Center Retrospective Study.” Medicina (Kaunas, Lithuania) (2026). PMID: 42195068 ↗
L3COHORTCited in: Definition, Classification, and Historical Context, Epidemiology and Risk Factors, Severity Grading and Risk Stratification
[8]
Comoglu E, Acehan F, Altiparmak E et al.. “Early identification of the need for biliary drainage in acute calculous cholangitis: a prospective cohort study.” European journal of gastroenterology & hepatology (2026). PMID: 41925043 ↗
L2COHORTCited in: Definition, Classification, and Historical Context, Severity Grading and Risk Stratification, Management of Underlying Etiologies, Complications and Long-term Outcomes
[9]
Chen QQ, Shao CK, Zhang YW et al.. “Clinicopathological features of hepatic Langerhans cell histiocytosis: report of ten cases and review of the literature.” Annals of diagnostic pathology (2026). PMID: 41264975 ↗
L4CASE_REPORTCited in: Definition, Classification, and Historical Context
[10]
Zheng J, Mo J, Xiong J et al.. “Sustained abnormal bilirubin and leukocyte levels after ERCP with acute suppurative obstructive cholangitis: a case report with 2 months follow-up observation.” Frontiers in immunology (2026). PMID: 41918747 ↗
L4CASE_REPORTCited in: Definition, Classification, and Historical Context, Biliary Decompression: Timing and Modalities
[11]
Kawata K, Inoue D, Komori T et al.. “Case of simultaneous occurrence of hepatitis, cholangitis, and pancreatitis as immune-related adverse events induced by immune checkpoint inhibitor therapy: a case report.” Abdominal radiology (New York) (2025). PMID: 40423705 ↗
L4CASE_REPORTCited in: Definition, Classification, and Historical Context, Laboratory and Radiologic Evaluation, Initial Medical Management and Antimicrobial Therapy
[12]
Calinescu AM, Wildhaber BE. “Post-Kasai cholangitis evaluation and management strategies: Review of the literature with insights from the Swiss Biliary Atresia Registry.” Seminars in pediatric surgery (2024). PMID: 39862689 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification, and Historical Context
[13]
Bergquist A, Ekstedt M, Hagström H et al.. “Forty years of successful national research collaboration in liver disease - the Swedish experience.” Scandinavian journal of gastroenterology (2024). PMID: 39485016 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification, and Historical Context
[14]
Kamezaki H, Iwanaga T, Maeda T et al.. “Risk of Pseudogallstones and Biliary Complications in Rehabilitation Patients Administered Ceftriaxone: A Retrospective Study.” JGH open : an open access journal of gastroenterology and hepatology (2025). PMID: 40589767 ↗
L4COHORTCited in: Definition, Classification, and Historical Context, Epidemiology and Risk Factors
[15]
Deng D, Yuan Q, Pan C et al.. “Non-invasive liquid biopsy based on metabolomic profiling improves diagnosis and early warning of severe acute pancreatitis.” NPJ digital medicine (2026). PMID: 41611815 ↗
L2OTHERCited in: Definition, Classification, and Historical Context
[16]
Hirschfield GM, Kowdley KV, Trivedi PJ et al.. “Phase II INTEGRIS-PSC trial of bexotegrast, an αvβ6/αvβ1 integrin inhibitor, in primary sclerosing cholangitis.” Journal of hepatology (2026). PMID: 41016442 ↗
L1RCTCited in: Epidemiology and Risk Factors
[17]
Yang Y, Wang Y, Chen Q et al.. “Analysis of the effectiveness and safety of endoscopic retrograde cholangiopancreatography versus percutaneous transhepatic biliary drainage in severe acute cholangitis caused by common bile duct stones.” Updates in surgery (2026). PMID: 40775581 ↗
L1RCTCited in: Epidemiology and Risk Factors, Biliary Decompression: Timing and Modalities, Alternative Decompression: PTBD and Surgical Intervention
[18]
Cristoferi L, D'Amato D, Maino C et al.. “Prospective, randomised, placebo-controlled, phase 2 clinical trial assessing the efficacy and safety of oral vancomycin in patients with primary sclerosing cholangitis with/out inflammatory bowel disease in Italy: study protocol of VanC-IT trial.” BMJ open (2026). PMID: 41513411 ↗
L5TRIAL_NONRANDOMCited in: Epidemiology and Risk Factors, Laboratory and Radiologic Evaluation, Initial Medical Management and Antimicrobial Therapy
[19]
Vitor IC, Tomé MR, Amador WFO et al.. “Primary Sclerosing Cholangitis Recurrence After Liver Transplantation: A Systematic Review and Updated Meta-Analysis.” Liver international : official journal of the International Association for the Study of the Liver (2026). PMID: 42163804 ↗
L2SR_OBSCited in: Epidemiology and Risk Factors
[20]
Desouky M, Altawil L, Al Hayek M et al.. “The efficacy and safety of magnetic compression anastomosis in the management of biliary obstruction: a systematic review and meta-analysis.” Surgical endoscopy (2026). PMID: 41651954 ↗
L2SR_OBSCited in: Epidemiology and Risk Factors, Management of Underlying Etiologies
[21]
Faleiro MD, de M Ogawa T, Correia PP et al.. “Updated Systematic Review and Meta-Analysis of Duct-to-duct Versus Hepaticojejunostomy Reconstruction After Liver Transplantation for Primary Sclerosing Cholangitis.” Transplantation (2026). PMID: 41572464 ↗
L2SR_OBSCited in: Epidemiology and Risk Factors, Complications and Long-term Outcomes
[22]
Garg A, Moond V, Garg A et al.. “Endoscopic balloon dilation versus stent placement in the management of dominant strictures in primary sclerosing cholangitis: a systematic review and meta-analysis.” Gastrointestinal endoscopy (2026). PMID: 40846243 ↗
L2SR_OBSCited in: Epidemiology and Risk Factors
[23]
Liu X, Wang Y, Han J et al.. “Risk factors for cholangitis after Kasai procedure in biliary atresia patients: a systematic review and meta-analysis.” International journal of surgery (London, England) (2025). PMID: 40844888 ↗
L2SR_OBSCited in: Epidemiology and Risk Factors
[24]
Chen ML, Wang XL, Yu H et al.. “Biliary stenting combined with intraluminal 125 I seed brachytherapy versus biliary stenting alone for the treatment of cholangiocarcinoma: a meta-analysis.” International journal of surgery (London, England) (2025). PMID: 40679970 ↗
L1SR_OBSCited in: Epidemiology and Risk Factors
[25]
Seeßle J, Ruhberg L, Kirchner M et al.. “Assessing the effect of single dose antibiotic prophylaxis compared with a multiday regimen in liver transplant recipients undergoing routine endoscopic retrograde cholangiopancreatography: a retrospective, single-centre, registry-based cohort study with a historical control group.” BMJ open gastroenterology (2026). PMID: 41974487 ↗
L3COHORTCited in: Epidemiology and Risk Factors, Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Severity Grading and Risk Stratification, Initial Medical Management and Antimicrobial Therapy, Biliary Decompression: Timing and Modalities, Complications and Long-term Outcomes
[26]
Älgå LL, Ekheden I, Thuresson M et al.. “Risk of primary sclerosing cholangitis among patients with gastritis: a nationwide cohort study.” European journal of epidemiology (2025). PMID: 40847211 ↗
L2COHORTCited in: Epidemiology and Risk Factors
[27]
Abdalla M, Eberhardson M, Landerholm K et al.. “Impact of Inflammatory Bowel Disease and Primary Sclerosing Cholangitis on Colorectal Cancer Risk: National Cohort Study.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2026). PMID: 40706734 ↗
L2COHORTCited in: Epidemiology and Risk Factors
[28]
Huang Y, Yin Z, Han W. “Anion gap associated with 28-days all-cause mortality in Acute cholangitis patients admitted to the intensive care unit in MIMIC-IV database: a retrospective cohort study.” Frontiers in medicine (2025). PMID: 40486199 ↗
L3COHORTCited in: Epidemiology and Risk Factors
[29]
Taniguchi J, Aso S, Matsui H et al.. “Association Between Ceftriaxone Use and Biliary Infections in Patients With Pneumonia: A Nationwide Retrospective Cohort Study.” Pharmacoepidemiology and drug safety (2025). PMID: 40398875 ↗
L3COHORTCited in: Epidemiology and Risk Factors, Initial Medical Management and Antimicrobial Therapy
[30]
Kulkarni C, Cholankeril G, Fardeen T et al.. “Statin Use Is Associated With Protection Against Acute Cholangitis in Patients With Primary Sclerosing Cholangitis: A Multicenter Retrospective Cohort Study.” Clinical and translational gastroenterology (2025). PMID: 40272937 ↗
L3COHORTCited in: Epidemiology and Risk Factors
[31]
Holmer M, Ingre M, Färkkilä M et al.. “Cirrhosis and age are key determinants of HCC risk in individuals with primary sclerosing cholangitis: A multicenter longitudinal cohort study.” Hepatology (Baltimore, Md.) (2026). PMID: 40238209 ↗
L2COHORTCited in: Epidemiology and Risk Factors, Management of Underlying Etiologies
[32]
Hof A, Rey R, Rock N et al.. “Etiology and management of cholangitis in pediatric liver transplant recipients: a systematic review.” Current opinion in organ transplantation (2026). PMID: 41947725 ↗
L2SR_OBSCited in: Epidemiology and Risk Factors, Laboratory and Radiologic Evaluation, Initial Medical Management and Antimicrobial Therapy
[33]
Zhang CC, Koschny R, Rupp C et al.. “Post-endoscopic retrograde cholangiopancreatography cholangitis after endoscopic treatment of post-transplant biliary strictures: a retrospective study.” BMC surgery (2025). PMID: 40783752 ↗
L3COHORTCited in: Epidemiology and Risk Factors, Biliary Decompression: Timing and Modalities
[34]
Vorasittha A, Sakamoto S, Yanagi Y et al.. “Recurrence of Primary Sclerosing Cholangitis After Pediatric Liver Transplantation: A Single-Center, Retrospective Study in Japan.” Pediatric transplantation (2025). PMID: 40217566 ↗
L4COHORTCited in: Epidemiology and Risk Factors
[35]
Wan Y, Zheng M, Fu W et al.. “Research trends on autoimmune liver diseases and gut microbiota (1989-2025): a bibliometric and visualization analysis based on the web of science core collection database.” Frontiers in immunology (2026). PMID: 42136643 ↗
L5OTHERCited in: Epidemiology and Risk Factors
[36]
An J, Ahn SH, Kim KH et al.. “Twenty-year temporal trends, risk profiles, and prognostic value of clinicopathological features in gallbladder cancer following cholecystectomy.” World journal of gastroenterology (2026). PMID: 41694497 ↗
L3OTHERCited in: Epidemiology and Risk Factors
[37]
Hiroshima Y, Sagami R, Kuraoka N et al.. “Sphincterotomy during endoscopic biliary drainage in cholangitis with sepsis-induced coagulopathy increases bleeding without clinical benefits.” Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (2026). PMID: 41656119 ↗
L3OTHERCited in: Epidemiology and Risk Factors, Biliary Decompression: Timing and Modalities
[38]
Elzubeir A, High J, Hammond M et al.. “Assessing brodalumab in the treatment of primary sclerosing cholangitis (SABR-PSC pilot study): protocol for a single-arm, multicentre, pilot study.” BMJ open gastroenterology (2025). PMID: 40032516 ↗
L5TRIAL_NONRANDOMCited in: Pathophysiology and Microbiology
[39]
Moniruzzaman M, Shah A, Fairlie T et al.. “Immune Activation in Primary Sclerosing Cholangitis: A Systematic Review and Comparative Analysis With Inflammatory Bowel Diseases.” United European gastroenterology journal (2025). PMID: 41026618 ↗
L2SR_OBSCited in: Pathophysiology and Microbiology
[40]
Halimi H, Hesami Z, Asri N et al.. “Exploring the biliary microbiome in hepatopancreatobiliary disorders: a comprehensive systematic review of microbial signatures and diagnostic potential.” BMC gastroenterology (2025). PMID: 41408188 ↗
L2SR_OBSCited in: Pathophysiology and Microbiology, Complications and Long-term Outcomes
[41]
Ledenko T, Sorić Hosman I, Ćorić M et al.. “Case Report: Simultaneously Developed Amyopathic Dermatomyositis and Autoimmune Sclerosing Cholangitis - a Coincidence or a Shared Immunopathogenesis?” Frontiers in immunology (2022). PMID: 35281002 ↗
L4CASE_REPORTCited in: Pathophysiology and Microbiology, Clinical Presentation and Physical Examination
[42]
Jalan-Sakrikar N, Anwar AA, Ali A et al.. “Cholangiocyte biology in primary sclerosing cholangitis and other cholangiopathies: pathogenesis, clinical insights, and experimental tools.” Physiological reviews (2026). PMID: 41973609 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[43]
Pan W, Yong Y, Li Y et al.. “Hepatocyte Mettl3 Deficiency Drives Primary Sclerosing Cholangitis and Liver Fibrosis via Cholangiocyte-Macrophage Crosstalk.” Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2026). PMID: 41431138 ↗
L5OTHERCited in: Pathophysiology and Microbiology
[44]
Das TS, Vuppalanchi R. “Future Treatment Options for Managing Primary Sclerosing Cholangitis and Cholestatic Pruritus.” Clinics in liver disease (2025). PMID: 41109703 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[45]
Wei S, Lu J. “Microbial Modulation of the Gut-Liver Axis in Autoimmune Liver Diseases.” Seminars in liver disease (2025). PMID: 40865561 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[46]
Grewal T, Tews HC, Buechler C. “Galectin-3-Insights from Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.” International journal of molecular sciences (2025). PMID: 40649879 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[47]
Kolev M, Kremer AE, Sokollik C et al.. “Unmet needs in autoimmune liver diseases.” Current opinion in immunology (2025). PMID: 40414140 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[48]
Kodilinye SM, Shiratori Y, Kalloo AN. “Avoiding the complications of endoscopic retrograde cholangiopancreatography.” Current opinion in gastroenterology (2025). PMID: 40402845 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[49]
Manns MP, Bergquist A, Karlsen TH et al.. “Primary sclerosing cholangitis.” Nature reviews. Disease primers (2025). PMID: 40082445 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[50]
Mizuno S, Uchida Y, Ando S et al.. “Endoscopic management of primary sclerosing cholangitis.” Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society (2025). PMID: 40049717 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology, Management of Underlying Etiologies
[51]
Noble A, Motta R, Cabras S et al.. “Epigenetic age acceleration and methylation differences in IgG4-related cholangitis and primary sclerosing cholangitis.” Clinical epigenetics (2025). PMID: 39819503 ↗
L3OTHERCited in: Pathophysiology and Microbiology
[52]
Bjornsson ES, Arnedillo D, Bessone F. “Secondary Sclerosing Cholangitis due to Drugs With a Special Emphasis on Checkpoint Inhibitors.” Liver international : official journal of the International Association for the Study of the Liver (2025). PMID: 39620448 ↗
L4REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[53]
Bjornsson ES, Devarbhavi HC. “Drug-induced cholestatic liver diseases.” Hepatology (Baltimore, Md.) (2025). PMID: 39121063 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[54]
Lammert F, Wittenburg H. “Gallstones: Prevention, Diagnosis, and Treatment.” Seminars in liver disease (2024). PMID: 39095030 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[55]
Dorner H, Stolzer I, Mattner J et al.. “Gut Pathobiont-Derived Outer Membrane Vesicles Drive Liver Inflammation and Fibrosis in Primary Sclerosing Cholangitis-Associated Inflammatory Bowel Disease.” Gastroenterology (2024). PMID: 38992449 ↗
L5OTHERCited in: Pathophysiology and Microbiology
[56]
Gassiep I, Edwards F, Laupland KB. “Epidemiology of biliary tract-associated bloodstream infections and adequacy of empiric therapy: an Australian population-based study.” European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (2024). PMID: 38985222 ↗
L2OTHERCited in: Pathophysiology and Microbiology
[57]
Kayashima A, Sujino T, Fukuhara S et al.. “Unique bile acid profiles in the bile ducts of patients with primary sclerosing cholangitis.” Hepatology communications (2024). PMID: 38780302 ↗
L3OTHERCited in: Pathophysiology and Microbiology
[58]
Motta RV, Saffioti F, Mavroeidis VK. “Hepatolithiasis: Epidemiology, presentation, classification and management of a complex disease.” World journal of gastroenterology (2024). PMID: 38659478 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[59]
Isogai M. “Pathophysiology of severe gallstone pancreatitis: A new paradigm.” World journal of gastroenterology (2024). PMID: 38515949 ↗
L5OTHERCited in: Pathophysiology and Microbiology
[60]
D'Amato D, Carbone M. “Prognostic models and autoimmune liver diseases.” Best practice & research. Clinical gastroenterology (2023). PMID: 38103932 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[61]
Nishiwaki R, Imoto I, Oka S et al.. “Elevated plasma and bile levels of corisin, a microbiota-derived proapoptotic peptide, in patients with severe acute cholangitis.” Gut pathogens (2023). PMID: 38037145 ↗
L3OTHERCited in: Pathophysiology and Microbiology
[62]
Houri I, Hirschfield GM. “Primary Biliary Cholangitis: Pathophysiology.” Clinics in liver disease (2024). PMID: 37945164 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[63]
Zapata M, Pagan-Torres H, Mayo MJ. “Systemic Complications of Primary Biliary Cholangitis.” Clinics in liver disease (2024). PMID: 37945153 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[64]
van Munster KN, Bergquist A, Ponsioen CY. “Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two?” Journal of hepatology (2024). PMID: 37940453 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[65]
Grama A, Mititelu A, Sîrbe C et al.. “Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets.” Frontiers in immunology (2023). PMID: 37928553 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology and Microbiology
[66]
Pratt HE, Wu T, Elhajjajy S et al.. “Beyond genome-wide association studies: Investigating the role of noncoding regulatory elements in primary sclerosing cholangitis.” Hepatology communications (2023). PMID: 37756045 ↗
L5OTHERCited in: Pathophysiology and Microbiology
[67]
Del Chierico F, Cardile S, Baldelli V et al.. “Characterization of the Gut Microbiota and Mycobiota in Italian Pediatric Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.” Inflammatory bowel diseases (2024). PMID: 37696680 ↗
L3OTHERCited in: Pathophysiology and Microbiology
[68]
Wang M, Harris A, McCulloch CE et al.. “Racial differences in primary sclerosing cholangitis: A retrospective cohort study leveraging a new ICD-10 code.” Annals of hepatology (2025). PMID: 40081809 ↗
L2COHORTCited in: Clinical Presentation and Physical Examination
[69]
Pi B, Wang J, Tong Y et al.. “Immune-related cholangitis induced by immune checkpoint inhibitors: a systematic review of clinical features and management.” European journal of gastroenterology & hepatology (2021). PMID: 34482313 ↗
L4SR_OBSCited in: Clinical Presentation and Physical Examination
[70]
Kunlayawutipong T, Pattarapuntakul T, Wong T et al.. “IgG4-related cholangitis - distinguishing from other benign biliary strictures: clinical features, imaging, and response to treatment: a retrospective study.” BMC gastroenterology (2025). PMID: 40640699 ↗
L3COHORTCited in: Clinical Presentation and Physical Examination, Laboratory and Radiologic Evaluation, Management of Underlying Etiologies
[71]
Chen Q, Kong D, Liu X. “Secondary sclerosing cholangitis due to drug-induced liver injury: a retrospective cohort study.” European journal of gastroenterology & hepatology (2025). PMID: 39621869 ↗
L3COHORTCited in: Clinical Presentation and Physical Examination
[72]
Kihara Y, Yokomizo H. “The clinical features of late postoperative cholangitis following pancreaticoduodenectomy brought on by conditions other than cancer recurrence: a single-center retrospective study.” BMC surgery (2022). PMID: 35932000 ↗
L3COHORTCited in: Clinical Presentation and Physical Examination
[73]
Li M, Wang A, Ren S et al.. “Factors associated with acute pancreatitis in patients with impacted duodenal papillary stones: a retrospective cohort study.” Scandinavian journal of gastroenterology (2022). PMID: 35297730 ↗
L3COHORTCited in: Clinical Presentation and Physical Examination
[74]
von Seth E, Karlsen TH, Tanaka A et al.. “Primary sclerosing cholangitis.” Lancet (London, England) (2026). PMID: 41871593 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation and Physical Examination
[75]
Chaouch MA, Dougaz MW, Bergaoui MM et al.. “Validation of charcot's triad and Tokyo guidelines 2018 as a diagnostic tool for acute ascending cholangitis secondary to a liver cystic echinococcosis.” BMC infectious diseases (2025). PMID: 41023890 ↗
L3OTHERCited in: Clinical Presentation and Physical Examination, Tokyo Guidelines 2018 (TG18) Diagnostic Criteria
[76]
Hue NT, Thi Huyen Trang N, Anh Tuan N et al.. “Delayed endoscopic retrograde cholangiopancreatography: a game-changer for acute cholangitis patients in a resource-limited setting.” Therapeutic advances in gastroenterology (2025). PMID: 40297202 ↗
L2OTHERCited in: Clinical Presentation and Physical Examination, Initial Medical Management and Antimicrobial Therapy
[77]
Yasuda T, Ito T, Ishikawa T et al.. “Clinical features and pathological findings by liver biopsy in patients with immune-related sclerosing cholangitis induced by immune checkpoint inhibitors.” Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (2025). PMID: 39828442 ↗
L3OTHERCited in: Clinical Presentation and Physical Examination
[78]
Jang Y, Kim JY, Han SY et al.. “Establishment of a chronic biliary disease mouse model with cholecystoduodenal anastomosis for intestinal microbiome preservation.” World journal of gastroenterology (2024). PMID: 39679313 ↗
L5OTHERCited in: Clinical Presentation and Physical Examination
[79]
Xu X, Meng T, Shi L et al.. “Prevalence and clinical profiles of primary sclerosing cholangitis in China: Data from electronic medical records and systematic literature retrieval.” Journal of autoimmunity (2024). PMID: 38843578 ↗
L2OTHERCited in: Clinical Presentation and Physical Examination
[80]
Thylin M, Färkkilä M, Kautiainen H et al.. “The new definition of dominant stricture in primary sclerosing cholangitis: Prevalence and clinical significance.” Liver international : official journal of the International Association for the Study of the Liver (2024). PMID: 38842451 ↗
L2OTHERCited in: Clinical Presentation and Physical Examination
[81]
Yamamoto T, Mizuno K, Ito T et al.. “Abdominal pain accompanied by elevated serum inflammatory markers and biliary enzymes for diagnosing immune checkpoint inhibitor-induced sclerosing cholangitis.” Investigational new drugs (2023). PMID: 37171720 ↗
L3OTHERCited in: Clinical Presentation and Physical Examination
[82]
Assis DN, Bowlus CL. “Recent Advances in the Management of Primary Sclerosing Cholangitis.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2023). PMID: 37084929 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation and Physical Examination
[83]
Morgan MA, Khot R, Sundaram KM et al.. “Primary sclerosing cholangitis: review for radiologists.” Abdominal radiology (New York) (2023). PMID: 36063181 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation and Physical Examination
[84]
Ludwig DR, Anderson MA, Itani M et al.. “Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis.” Abdominal radiology (New York) (2023). PMID: 35585354 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation and Physical Examination
[85]
Tian S, Li K, Tang H et al.. “Clinical characteristics of Gram-negative and Gram-positive bacterial infection in acute cholangitis: a retrospective observational study.” BMC infectious diseases (2022). PMID: 35307004 ↗
L3OTHERCited in: Clinical Presentation and Physical Examination
[86]
Yokoe M, Takada T, Strasberg SM et al.. “TG13 diagnostic criteria and severity grading of acute cholecystitis (with videos).” Journal of hepato-biliary-pancreatic sciences (2013). PMID: 23340953 ↗
L1GUIDELINECited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Severity Grading and Risk Stratification, Landmark Evidence and Guideline Evolution
[87]
Higuchi R, Takada T, Strasberg SM et al.. “TG13 miscellaneous etiology of cholangitis and cholecystitis.” Journal of hepato-biliary-pancreatic sciences (2013). PMID: 23307005 ↗
L1GUIDELINECited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Landmark Evidence and Guideline Evolution
[88]
Kiriyama S, Takada T, Strasberg SM et al.. “TG13 guidelines for diagnosis and severity grading of acute cholangitis (with videos).” Journal of hepato-biliary-pancreatic sciences (2013). PMID: 23307001 ↗
L1GUIDELINECited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Severity Grading and Risk Stratification, Landmark Evidence and Guideline Evolution
[89]
Yokoe M, Takada T, Strasberg SM et al.. “New diagnostic criteria and severity assessment of acute cholecystitis in revised Tokyo Guidelines.” Journal of hepato-biliary-pancreatic sciences (2012). PMID: 22872303 ↗
L1GUIDELINECited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Severity Grading and Risk Stratification, Landmark Evidence and Guideline Evolution
[90]
Kiriyama S, Takada T, Strasberg SM et al.. “New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo Guidelines.” Journal of hepato-biliary-pancreatic sciences (2012). PMID: 22825491 ↗
L1GUIDELINECited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Severity Grading and Risk Stratification, Landmark Evidence and Guideline Evolution
[91]
Overdevest AG, Sieswerda E, Haal S et al.. “Antibiotic treatment for 1 day versus 4-7 days in patients with acute cholangitis after adequate endoscopic biliary drainage (COBRA): study protocol for a randomized controlled trial.” Trials (2026). PMID: 41689066 ↗
L1TRIAL_NONRANDOMCited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Initial Medical Management and Antimicrobial Therapy, Biliary Decompression: Timing and Modalities, Complications and Long-term Outcomes
[92]
Mayumi T, Takada T, Kawarada Y et al.. “Results of the Tokyo Consensus Meeting Tokyo Guidelines.” Journal of hepato-biliary-pancreatic surgery (2007). PMID: 17252304 ↗
L1GUIDELINECited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Landmark Evidence and Guideline Evolution
[93]
Yasuda H, Takada T, Kawarada Y et al.. “Unusual cases of acute cholecystitis and cholangitis: Tokyo Guidelines.” Journal of hepato-biliary-pancreatic surgery (2007). PMID: 17252303 ↗
L1GUIDELINECited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Landmark Evidence and Guideline Evolution
[94]
Wada K, Takada T, Kawarada Y et al.. “Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines.” Journal of hepato-biliary-pancreatic surgery (2007). PMID: 17252297 ↗
L1GUIDELINECited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Landmark Evidence and Guideline Evolution
[95]
Miura F, Takada T, Kawarada Y et al.. “Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines.” Journal of hepato-biliary-pancreatic surgery (2007). PMID: 17252294 ↗
L1GUIDELINECited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria
[96]
He YQ, Wang H, Zhao YH et al.. “Nomogram for assistant diagnosing acute suppurative cholangitis: a case-control study.” BMC gastroenterology (2024). PMID: 39304833 ↗
L3CASE_CONTROLCited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria
[97]
Ucdal M, Ekingen E. “Performance comparison of a neuro-symbolic large language model system versus conventional AI models and human experts in cholangitis management.” BMC medical informatics and decision making (2026). PMID: 42226236 ↗
L4OTHERCited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria
[98]
Martínez Márquez RJ, Cienfuegos Alvear JA, Torres Monarrez AA et al.. “Acute cholecystitis and acute cholangitis: the radiologist's role in diagnosis and management.” Abdominal radiology (New York) (2026). PMID: 40728645 ↗
L5REVIEW_NARRATIVECited in: Tokyo Guidelines 2018 (TG18) Diagnostic Criteria, Laboratory and Radiologic Evaluation
[99]
Kiriyama S, Kozaka K, Takada T et al.. “Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos).” Journal of hepato-biliary-pancreatic sciences (2018). PMID: 29032610 ↗
L1SR_OBSCited in: Severity Grading and Risk Stratification
[100]
Lu ZQ, Zhang HY, Su CF et al.. “Optimal timing of biliary drainage based on the severity of acute cholangitis: A single-center retrospective cohort study.” World journal of gastroenterology (2022). PMID: 36157549 ↗
L2COHORTCited in: Severity Grading and Risk Stratification
[101]
Umefune G, Kogure H, Hamada T et al.. “Procalcitonin is a useful biomarker to predict severe acute cholangitis: a single-center prospective study.” Journal of gastroenterology (2017). PMID: 27783206 ↗
L2COHORTCited in: Severity Grading and Risk Stratification
[102]
Yokoe M, Hata J, Takada T et al.. “Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis (with videos).” Journal of hepato-biliary-pancreatic sciences (2018). PMID: 29032636 ↗
L1REVIEW_NARRATIVECited in: Severity Grading and Risk Stratification
[103]
Miura F, Okamoto K, Takada T et al.. “Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis.” Journal of hepato-biliary-pancreatic sciences (2018). PMID: 28941329 ↗
L1REVIEW_NARRATIVECited in: Severity Grading and Risk Stratification
[104]
Sun G, Han L, Yang Y et al.. “Comparison of two editions of Tokyo guidelines for the management of acute cholangitis.” Journal of hepato-biliary-pancreatic sciences (2014). PMID: 23813895 ↗
L3OTHERCited in: Severity Grading and Risk Stratification
[105]
Kiriyama S, Takada T, Hwang TL et al.. “Clinical application and verification of the TG13 diagnostic and severity grading criteria for acute cholangitis: an international multicenter observational study.” Journal of hepato-biliary-pancreatic sciences (2017). PMID: 28419764 ↗
L3OTHERCited in: Severity Grading and Risk Stratification
[106]
Sornsenee P, Chaochuensuk C, Sapsong D et al.. “Development and internal validation of a risk stratification scoring system for identifying gram-negative ESBL-positive acute cholangitis: A retrospective cohort study.” PloS one (2026). PMID: 41843577 ↗
L3COHORTCited in: Severity Grading and Risk Stratification
[107]
Nakamura A, Watanabe K, Sato W et al.. “Timing of Biliary Drainage and Clinical Outcomes in Acute Cholangitis: A Single-Center Retrospective Cohort Study.” Cureus (2026). PMID: 42005126 ↗
L3COHORTCited in: Severity Grading and Risk Stratification
[108]
Hashemi P, Boyer JL, Langdon JH. “The Utility of Elastography in Discriminating Stages of Liver Fibrosis and Risk Stratification in Patients With Primary Sclerosing Cholangitis: A Systematic Review.” Journal of magnetic resonance imaging : JMRI (2026). PMID: 41709322 ↗
L2SR_OBSCited in: Laboratory and Radiologic Evaluation, Complications and Long-term Outcomes
[109]
Shah Y, Singh S, Dahiya DS et al.. “Endoscopic Ultrasound-Guided Biliary Drainage for Acute Cholangitis Secondary to Biliary Obstruction: A Systematic Review and Meta-Analysis.” Surgical laparoscopy, endoscopy & percutaneous techniques (2025). PMID: 40548485 ↗
L1SR_OBSCited in: Laboratory and Radiologic Evaluation, Biliary Decompression: Timing and Modalities
[110]
Vuppalanchi R, Akisik F, Pansini M et al.. “The Prognostic Utility of Quantitative Magnetic Resonance Cholangiopancreatography in Patients With PSC: A Systematic Review With Structured Evidence Synthesis.” Journal of computer assisted tomography (Unknown). PMID: 41488989 ↗
L2SR_OBSCited in: Laboratory and Radiologic Evaluation
[111]
Dupont B, Dejardin O, Kam W et al.. “Impact of timing of access to endoscopic drainage and social determinants of health on the prognosis of patients with periampullary cancer diagnosed through jaundice: a multicenter retrospective study.” Therapeutic advances in gastroenterology (2026). PMID: 41777617 ↗
L3COHORTCited in: Laboratory and Radiologic Evaluation, Biliary Decompression: Timing and Modalities, Complications and Long-term Outcomes
[112]
Yang Y, Hou Y, Wang Y et al.. “Diagnostic pitfalls in IgG4-related sclerosing cholangitis presenting as perihilar cholangiocarcinoma: case report with literature review.” Frontiers in immunology (2026). PMID: 42079574 ↗
L4CASE_REPORTCited in: Laboratory and Radiologic Evaluation
[113]
Liu YA, Gao X, Gao W et al.. “IgG4-sclerosing cholangitis masquerading as cholangiocarcinoma: a case report of an unresolved preoperative diagnosis.” Frontiers in immunology (2026). PMID: 42004961 ↗
L4CASE_REPORTCited in: Laboratory and Radiologic Evaluation
[114]
Lazzari R, Borja Cano M, Rivera Martínez A et al.. “Vibrio fluvialis cholangitis with bacteremia and refractory septic shock: a case report and review of the literature.” Infection (2025). PMID: 40377851 ↗
L4CASE_REPORTCited in: Laboratory and Radiologic Evaluation, Initial Medical Management and Antimicrobial Therapy
[115]
Vazzana GF, Romano C, Del Prete S et al.. “Autoimmune liver diseases and overlap syndromes in children with inflammatory bowel diseases.” European journal of pediatrics (2026). PMID: 42035371 ↗
L5REVIEW_NARRATIVECited in: Laboratory and Radiologic Evaluation
[116]
Martins A, Reddy A, Dean R et al.. “Gaps in Guideline Adherence for Primary Sclerosing Cholangitis in North America-A 5-Year Analysis.” Liver international : official journal of the International Association for the Study of the Liver (2026). PMID: 41964270 ↗
L3OTHERCited in: Laboratory and Radiologic Evaluation, Management of Underlying Etiologies
[117]
Naitoh I, Nakazawa T, Kubota K et al.. “Multicenter Validation Study of the Clinical Diagnostic Criteria for IgG4-Related Sclerosing Cholangitis 2020 in Japan.” Journal of hepato-biliary-pancreatic sciences (2026). PMID: 41500843 ↗
L3OTHERCited in: Laboratory and Radiologic Evaluation
[118]
Tanaka A, Treeprasertsuk S, Chang ML et al.. “Autoimmune liver diseases in the Asia Pacific region: proceedings of the autoimmune liver disease course at APASL 2025.” Hepatology international (2026). PMID: 41326940 ↗
L5REVIEW_NARRATIVECited in: Laboratory and Radiologic Evaluation
[119]
Cruz Grave E, Chan C, Corwin MT et al.. “Spatial heterogeneity in liver stiffness does not predict clinical outcomes in patients with primary sclerosing cholangitis.” Hepatology communications (2025). PMID: 41099629 ↗
L3OTHERCited in: Laboratory and Radiologic Evaluation
[120]
Cristoferi L, Maino C, Bernasconi DP et al.. “Radiomics-Based Prognostication in Primary Sclerosing Cholangitis: A Proof-of-Concept Study.” Liver international : official journal of the International Association for the Study of the Liver (2025). PMID: 41014131 ↗
L2OTHERCited in: Laboratory and Radiologic Evaluation
[121]
Levers A, Pantke J, Klimeš F et al.. “Sarcopenia-A Valuable Imaging Biomarker for Disease Progression in Patients With Primary Sclerosing Cholangitis (PSC)?” Liver international : official journal of the International Association for the Study of the Liver (2025). PMID: 40922637 ↗
L3OTHERCited in: Laboratory and Radiologic Evaluation
[122]
Altenmüller J, Wiegard C, Sebode M et al.. “Ultrasound for the Detection of Gallbladder Malignancy in Primary Sclerosing Cholangitis.” Liver international : official journal of the International Association for the Study of the Liver (2025). PMID: 40856347 ↗
L3OTHERCited in: Laboratory and Radiologic Evaluation
[123]
Kum VTL, Yeung F, Chung PHY et al.. “Cholangitis is associated with liver fibrosis in choledochal malformations.” Journal of pediatric surgery (2026). PMID: 40783022 ↗
L3OTHERCited in: Laboratory and Radiologic Evaluation
[124]
Lytvyak E, Hirschfield G, Shreekumar D et al.. “Pathogenesis, Non-Invasive Assessments and Treatment of Hepatic Fibrosis in Autoimmune Liver Diseases.” Liver international : official journal of the International Association for the Study of the Liver (2025). PMID: 40682413 ↗
L5REVIEW_NARRATIVECited in: Laboratory and Radiologic Evaluation, Biliary Decompression: Timing and Modalities
[125]
Motor J, Gajewska A, Cienkowski K et al.. “IgG4-related disease - focus on digestive system involvement.” Frontiers in immunology (2025). PMID: 40612937 ↗
L5REVIEW_NARRATIVECited in: Laboratory and Radiologic Evaluation
[126]
Naitoh I, Isayama H, Akamatsu N et al.. “The 2024 diagnostic criteria for primary sclerosing cholangitis.” Journal of gastroenterology (2025). PMID: 40504416 ↗
L1REVIEW_NARRATIVECited in: Laboratory and Radiologic Evaluation
[127]
Berhane B, van de Put WS, van Rheenen PF. “Gamma-glutamyltransferase testing in paediatric inflammatory bowel disease to screen for primary sclerosing cholangitis: a diagnostic study based on routinely collected electronic healthcare data.” Archives of disease in childhood (2025). PMID: 40412823 ↗
L2OTHERCited in: Laboratory and Radiologic Evaluation
[128]
Beuers U, Trampert DC. “IgG4-Related Cholangitis.” Seminars in liver disease (2025). PMID: 40342085 ↗
L5REVIEW_NARRATIVECited in: Laboratory and Radiologic Evaluation
[129]
Ippolito D, Maino C, Arrivé L et al.. “ESGAR consensus statement on MR imaging in primary sclerosing cholangitis.” European radiology (2025). PMID: 40285815 ↗
L1OTHERCited in: Laboratory and Radiologic Evaluation
[130]
Buhot Q, Bui Q, Chekir H et al.. “MR imaging and cholangiography show suboptimal performance for diagnosing ductal cholangiocarcinoma in primary sclerosing cholangitis patients.” European radiology (2025). PMID: 40285814 ↗
L3OTHERCited in: Laboratory and Radiologic Evaluation
[131]
Lee TS, Choi JH, Lee JM et al.. “A randomized non-inferiority trial investigating antibiotic adjustments based on blood culture in acute cholangitis.” Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (2025). PMID: 39880122 ↗
L1RCTCited in: Initial Medical Management and Antimicrobial Therapy
[132]
Habib T, Lahoud C, Moussa E et al.. “Prophylactic Antibiotics Reduce Infectious Complications After ERCP in Patients with Suspected Biliary Obstruction: A Meta-Analysis of Randomized Controlled Trials.” Digestive diseases and sciences (2026). PMID: 41134425 ↗
L1SR_MA_RCTCited in: Initial Medical Management and Antimicrobial Therapy, Biliary Decompression: Timing and Modalities, Complications and Long-term Outcomes
[133]
Arbabzada N, Dennett L, Meng G et al.. “The Effectiveness of Oral Vancomycin on Inflammatory Bowel Disease in Patients With Primary Sclerosing Cholangitis: A Systematic Review.” Inflammatory bowel diseases (2025). PMID: 39495039 ↗
L2SR_OBSCited in: Initial Medical Management and Antimicrobial Therapy
[134]
Bonomi A, Overdevest AG, Busch OR et al.. “Towards a 'step-up approach' for the treatment of recurrent non-stenotic cholangitis after hepaticojejunostomy: systematic review.” HPB : the official journal of the International Hepato Pancreato Biliary Association (2024). PMID: 38906773 ↗
L4SR_OBSCited in: Initial Medical Management and Antimicrobial Therapy
[135]
Kaneko J, Takinami M, Anma A et al.. “Clinical Characteristics and Predictors of Acute Cholangitis With Enterococcal-Positive Bile Cultures: A Retrospective Study.” Journal of hepato-biliary-pancreatic sciences (2025). PMID: 40984738 ↗
L3COHORTCited in: Initial Medical Management and Antimicrobial Therapy, Complications and Long-term Outcomes
[136]
Brody Y, Slae M, Amir AZ et al.. “Primary antibiotic prophylaxis in biliary atresia did not demonstrate decreased infection rate: Multi-centre retrospective study.” Acta paediatrica (Oslo, Norway : 1992) (2025). PMID: 39528247 ↗
L3COHORTCited in: Initial Medical Management and Antimicrobial Therapy
[137]
Masuda S, Imamura Y, Kimura K et al.. “Optimizing short-term antibiotic treatment in patients with acute cholangitis: study protocol for an open-label randomized controlled trial (the BOLT-P3 trial).” Trials (2025). PMID: 40890775 ↗
L5TRIAL_NONRANDOMCited in: Initial Medical Management and Antimicrobial Therapy, Biliary Decompression: Timing and Modalities
[138]
Smith E, Wu Y, Adamson C et al.. “Is Antibiotic Prophylaxis Warranted in All Patients With Biliary Obstruction Undergoing Endoscopic Retrograde Cholangiopancreatography?: A Systematic Review and Meta-Analysis.” Journal of clinical gastroenterology (Unknown). PMID: 40961256 ↗
L1SR_OBSCited in: Initial Medical Management and Antimicrobial Therapy, Biliary Decompression: Timing and Modalities, Complications and Long-term Outcomes
[139]
García-Marmolejo JP, Diaz-Brochero C, Nocua-Báez LC et al.. “Differences in clinical outcomes according to duration of antibiotic therapy following successful ERCP in patients with acute cholangitis: A retrospective cohort study in Colombia.” Infectious diseases now (2025). PMID: 41176092 ↗
L3COHORTCited in: Initial Medical Management and Antimicrobial Therapy, Biliary Decompression: Timing and Modalities, Complications and Long-term Outcomes
[140]
Takai S, Todaka T. “Acute liver failure as a rare presentation of miliary tuberculosis with clinical improvement following prediagnostic corticosteroid therapy: A case report.” International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (2026). PMID: 41224108 ↗
L4CASE_REPORTCited in: Initial Medical Management and Antimicrobial Therapy, Biliary Decompression: Timing and Modalities
[141]
Kodana M, Imai K, Takayama T et al.. “Acute cholangitis caused by coinfection with zoonotic pathogens of Gallibacterium anatis and Enterococcus cecorum: A case report.” International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (2025). PMID: 39510311 ↗
L4CASE_REPORTCited in: Initial Medical Management and Antimicrobial Therapy
[142]
Keshi E, Siemund F, Knitter S et al.. “Differential effects of preoperative cholangitis and biliary stenting in long-term survival of patients undergoing surgery for perihilar cholangiocarcinoma.” European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology (2026). PMID: 41672022 ↗
L3OTHERCited in: Initial Medical Management and Antimicrobial Therapy
[143]
Satoh T, Takahashi H, Nakatani E et al.. “Impact of Peri-Procedural Antibiotics on Post-ERCP Infectious Adverse Events With Distal Malignant Biliary Obstruction.” Journal of gastroenterology and hepatology (2026). PMID: 41466488 ↗
L3OTHERCited in: Initial Medical Management and Antimicrobial Therapy, Biliary Decompression: Timing and Modalities
[144]
Choquet A, Sokal A, Dokmak S et al.. “Recurrent Nonobstructive Cholangitis After Pancreaticoduodenectomy: Prevalence, Risk Factors, and Treatment.” World journal of surgery (2025). PMID: 40776530 ↗
L3OTHERCited in: Initial Medical Management and Antimicrobial Therapy
[145]
Cozma MA, Găman MA, Diaconu CC et al.. “Microbial Profile and Antibiotic Resistance Patterns in Bile Aspirates from Patients with Acute Cholangitis: A Multicenter International Study.” Antibiotics (Basel, Switzerland) (2025). PMID: 40723982 ↗
L2OTHERCited in: Initial Medical Management and Antimicrobial Therapy
[146]
Fortún J, Rodríguez-Gandía MA, Pintado V et al.. “Oral nonabsorbable antibiotics for prevention of recurrent cholangitis; a brief report study.” Infection (2025). PMID: 39976806 ↗
L4OTHERCited in: Initial Medical Management and Antimicrobial Therapy
[147]
Räisänen L, Balouch F, McLaren-Kennedy A et al.. “Outcomes of oral vancomycin therapy in children with atypical ulcerative colitis with or without confirmed primary sclerosing cholangitis: a real-world observational study.” BMJ open gastroenterology (2025). PMID: 39938966 ↗
L3OTHERCited in: Initial Medical Management and Antimicrobial Therapy
[148]
Jagtap N, Rughwani H, Talukdar R et al.. “Urgent versus early ERCP in mild-to-moderate acute cholangitis: a randomised controlled trial.” Gut (2026). PMID: 42161575 ↗
L1RCTCited in: Biliary Decompression: Timing and Modalities, Complications and Long-term Outcomes
[149]
Peppas S, Suvarnakar A, Abujaber BA et al.. “Endoscopic ultrasound-guided biliary drainage versus endoscopic retrograde cholangiopancreatography biliary drainage in the palliative management of malignant distal biliary obstruction: an updated systematic review and meta-analysis of randomized controlled trials.” Clinical endoscopy (2025). PMID: 40340260 ↗
L1SR_MA_RCTCited in: Biliary Decompression: Timing and Modalities
[150]
Gungabissoon U, Hunnicutt J, McDermott EJ et al.. “Pruritus and health-related quality of life in chronic liver disease: a longitudinal, survey-based cohort study.” BMJ open gastroenterology (2025). PMID: 41381205 ↗
L2COHORTCited in: Biliary Decompression: Timing and Modalities
[151]
Chittajallu V, Elangovan A, Abu Omar Y et al.. “Biliary endoscopic drainage of septic ICU patients deemed emergent (BEDSIDE): a retrospective cohort study (2012-2022).” BMC gastroenterology (2026). PMID: 42168878 ↗
L4COHORTCited in: Biliary Decompression: Timing and Modalities, Complications and Long-term Outcomes
[152]
Liu Z, Wang A, Cao Y et al.. “Case Report: A steroid-sparing mechanical management of IgG4-related sclerosing cholangitis mimicking cholangiocarcinoma.” Frontiers in immunology (2026). PMID: 42112333 ↗
L4CASE_REPORTCited in: Biliary Decompression: Timing and Modalities, Management of Underlying Etiologies
[153]
Hsin KH, Tseng HH, Wang HP et al.. “Salvage Endoscopic Management for Basket Impaction Using Cholangioscopy and Electrohydraulic Lithotripsy.” Journal of gastroenterology and hepatology (2025). PMID: 40400219 ↗
L4CASE_REPORTCited in: Biliary Decompression: Timing and Modalities, Management of Underlying Etiologies
[154]
Tavakkoli A, Kapinos KA, Kwon RS et al.. “Variations in Incidence and Financial Burdens of Nonpancreatic Postendoscopic Retrograde Cholangiopancreatography Adverse Events.” Clinical and translational gastroenterology (2026). PMID: 41410317 ↗
L2OTHERCited in: Biliary Decompression: Timing and Modalities
[155]
He JL, Zhu L, Yang ZZ et al.. “Efficacy and Safety of Endoscopic Retrograde Cholangiopancreatography for the Longevous Population.” Clinical interventions in aging (2025). PMID: 41200531 ↗
L3OTHERCited in: Biliary Decompression: Timing and Modalities
[156]
Baydoun H, Beran A, Ramai D et al.. “Advanced chronic kidney disease increases the odds of ERCP adverse events but not post-ERCP pancreatitis: a propensity-matched analysis of the US Collaborative Network.” Surgical endoscopy (2026). PMID: 41125933 ↗
L3OTHERCited in: Biliary Decompression: Timing and Modalities
[157]
Kongsakon R, Rugivarodom M, Phisalprapa P et al.. “Urgent endoscopic retrograde cholangiopancreatography improves clinical outcomes in acute cholangitis from choledocholithiasis: a propensity score-matched study.” Surgical endoscopy (2025). PMID: 41023220 ↗
L3OTHERCited in: Biliary Decompression: Timing and Modalities
[158]
Johnston TM, Lamb CR, Jo A et al.. “Missed opportunities for laparoscopic common bile duct exploration (LCBDE): we can do better.” Surgical endoscopy (2025). PMID: 40935940 ↗
L4OTHERCited in: Biliary Decompression: Timing and Modalities
[159]
Xia JY, Komanduri S, Keswani RN et al.. “Integrating multi-omics in bile for biomarker discovery in cholangiocarcinoma.” Hepatology communications (2025). PMID: 40857390 ↗
L4OTHERCited in: Biliary Decompression: Timing and Modalities
[160]
Cho E, Park SW, Lee KJ et al.. “Drainage-only strategy on weekend for endoscopic retrograde cholangiopancreatography on the risk of procedure-related adverse events: a prospective observational study.” Therapeutic advances in gastroenterology (2025). PMID: 40821740 ↗
L2OTHERCited in: Biliary Decompression: Timing and Modalities
[161]
Sheng Y, Xu S, Zhang S et al.. “The relationship between clinical subtypes, prognosis, and treatment in ICU patients with acute cholangitis using unsupervised machine learning methods.” BMC infectious diseases (2025). PMID: 40760727 ↗
L2OTHERCited in: Biliary Decompression: Timing and Modalities
[162]
Volkovetskii V, Lobanova O, Puzyr N et al.. “Laparoscopic common bile duct exploration vs endoscopic retrograde cholangiopancreatography for the treatment of difficult common bile duct stones: postsurgery inflammation and liver function.” Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract (2025). PMID: 40683590 ↗
L3OTHERCited in: Biliary Decompression: Timing and Modalities
[163]
Mukund A, Choudhury A, Das S et al.. “Salvage PTBD in post living donor liver transplant patients with biliary complications-a single centre retrospective study.” The British journal of radiology (2020). PMID: 31971831 ↗
L4COHORTCited in: Alternative Decompression: PTBD and Surgical Intervention
[164]
Moll CF, de Moura DTH, Ribeiro IB et al.. “Endoscopic Biliary Darinage (EBD) versus Percutaneous Transhepatic Biliary Drainage (PTBD) for biliary drainage in patients with Perihilar Cholangiocarcinoma (PCCA): A systematic review and meta-analysis.” Clinics (Sao Paulo, Brazil) (2023). PMID: 36681067 ↗
L1SR_OBSCited in: Alternative Decompression: PTBD and Surgical Intervention
[165]
Al Mahjoub A, Menahem B, Fohlen A et al.. “Preoperative Biliary Drainage in Patients with Resectable Perihilar Cholangiocarcinoma: Is Percutaneous Transhepatic Biliary Drainage Safer and More Effective than Endoscopic Biliary Drainage? A Meta-Analysis.” Journal of vascular and interventional radiology : JVIR (2017). PMID: 28343588 ↗
L2SR_OBSCited in: Alternative Decompression: PTBD and Surgical Intervention
[166]
Tang Z, Yang Y, Meng W et al.. “Best option for preoperative biliary drainage in Klatskin tumor: A systematic review and meta-analysis.” Medicine (2017). PMID: 29069029 ↗
L2SR_OBSCited in: Alternative Decompression: PTBD and Surgical Intervention
[167]
Chen GF, Yu WD, Wang JR et al.. “The methods of preoperative biliary drainage for resectable hilar cholangiocarcinoma patients: A protocol for systematic review and meta analysis.” Medicine (2020). PMID: 32481299 ↗
L2SR_OBSCited in: Alternative Decompression: PTBD and Surgical Intervention
[168]
Lynn PB, Warnack EM, Parikh M et al.. “Hemobilia as a Complication of Transhepatic Percutaneous Biliary Drainage: a Rare Indication for Laparoscopic Common Bile Duct Exploration.” Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract (2020). PMID: 32607858 ↗
L4CASE_REPORTCited in: Alternative Decompression: PTBD and Surgical Intervention
[169]
Shapera E, Ross S, Pattilachan T et al.. “Robotic Biliary Stricturoplasty and Roux-en-Y Hepaticojejunostomy After Hepatic Artery Infusion Pump Injury.” Annals of surgical oncology (2024). PMID: 38632219 ↗
L4CASE_REPORTCited in: Alternative Decompression: PTBD and Surgical Intervention
[170]
Tsuchiya T, Sofuni A, Tsuji S et al.. “Endoscopic management of acute cholangitis according to the TG13.” Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society (2017). PMID: 28425666 ↗
L1REVIEW_NARRATIVECited in: Alternative Decompression: PTBD and Surgical Intervention
[171]
Yonem O, Bayraktar Y. “Clinical characteristics of Caroli's syndrome.” World journal of gastroenterology (2007). PMID: 17461493 ↗
L5REVIEW_NARRATIVECited in: Alternative Decompression: PTBD and Surgical Intervention
[172]
Ramchandani M, Pal P, Reddy DN. “Endoscopic management of acute cholangitis as a result of common bile duct stones.” Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society (2017). PMID: 28425658 ↗
L5REVIEW_NARRATIVECited in: Alternative Decompression: PTBD and Surgical Intervention
[173]
Liao YJ, Lin WT, Tsai HJ et al.. “Critically-Ill Patients with Biliary Obstruction and Cholangitis: Bedside Fluoroscopic-Free Endoscopic Drainage versus Percutaneous Drainage.” Journal of clinical medicine (2022). PMID: 35407477 ↗
L3OTHERCited in: Alternative Decompression: PTBD and Surgical Intervention
[174]
Gupta P, Maralakunte M, Kalra N et al.. “Feasibility and safety of bedside percutaneous biliary drainage in patients with severe cholangitis.” Abdominal radiology (New York) (2021). PMID: 33095311 ↗
L4OTHERCited in: Alternative Decompression: PTBD and Surgical Intervention
[175]
Hamada T, Tsujino T, Isayama H et al.. “Percutaneous transhepatic biliary drainage using a ligated catheter for recurrent catheter obstruction: antireflux technique.” Gut and liver (2013). PMID: 23560165 ↗
L4OTHERCited in: Alternative Decompression: PTBD and Surgical Intervention
[176]
Kim JH. “Clinical feasibility and usefulness of CT fluoroscopy-guided percutaneous transhepatic biliary drainage in emergency patients with acute obstructive cholangitis.” Korean journal of radiology (2009). PMID: 19270860 ↗
L4OTHERCited in: Alternative Decompression: PTBD and Surgical Intervention
[177]
Ahn S, Lee YS, Lim KS et al.. “Malignant biliary obstructions: can we predict immediate postprocedural cholangitis after percutaneous biliary drainage?” Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer (2013). PMID: 23529668 ↗
L3OTHERCited in: Alternative Decompression: PTBD and Surgical Intervention
[178]
Jung HM, Paik J, Lee M et al.. “Clinical Utility of the Tokyo Guidelines 2018 for Acute Cholangitis in the Emergency Department and Comparison with Novel Markers (Neutrophil-to-Lymphocyte and Blood Nitrogen Urea-to-Albumin Ratios).” Journal of clinical medicine (2024). PMID: 38673579 ↗
L3OTHERCited in: Alternative Decompression: PTBD and Surgical Intervention
[179]
Chiu HC, Liu CA, Tseng HS et al.. “Predictors of technical success of percutaneous transhepatic common bile duct stone removal: is it only a matter of stone size?” European radiology (2023). PMID: 37081299 ↗
L3OTHERCited in: Alternative Decompression: PTBD and Surgical Intervention
[180]
O'Brien S, Bhutiani N, Egger ME et al.. “Comparing the efficacy of initial percutaneous transhepatic biliary drainage and endoscopic retrograde cholangiopancreatography with stenting for relief of biliary obstruction in unresectable cholangiocarcinoma.” Surgical endoscopy (2020). PMID: 31139984 ↗
L3OTHERCited in: Alternative Decompression: PTBD and Surgical Intervention
[181]
Kim KM, Park JW, Lee JK et al.. “A Comparison of Preoperative Biliary Drainage Methods for Perihilar Cholangiocarcinoma: Endoscopic versus Percutaneous Transhepatic Biliary Drainage.” Gut and liver (2015). PMID: 26087784 ↗
L3OTHERCited in: Alternative Decompression: PTBD and Surgical Intervention
[182]
Grikyte I, Ignatavicius P. “Risk assessment of gallbladder cancer in patients with primary sclerosing cholangitis and gallbladder polyps: a systematic review.” Langenbeck's archives of surgery (2025). PMID: 40632214 ↗
L3SR_OBSCited in: Management of Underlying Etiologies
[183]
Bejaoui I, Maatouk M, Kbir GH et al.. “Is Laparoscopic Common Bile Duct Exploration Safe in Patients with Acute Cholangitis Caused by Common Bile Duct Stones? Results of a Systematic Review.” Journal of laparoendoscopic & advanced surgical techniques. Part A (2025). PMID: 39761129 ↗
L2SR_OBSCited in: Management of Underlying Etiologies
[184]
Liao Y, Liu F, Zhang X et al.. “The safety and efficacy of primary duct closure after laparoscopic common bile duct exploration in patients with mild-to-moderate calculus-associated acute cholangitis: a retrospective cohort study.” Updates in surgery (2024). PMID: 39581941 ↗
L3COHORTCited in: Management of Underlying Etiologies
[185]
Escobar JC, Pereyra MN, Abbass MA. “Primary Sclerosing Cholangitis and Inflammatory Bowel Disease.” The Surgical clinics of North America (2025). PMID: 40015822 ↗
L5REVIEW_NARRATIVECited in: Management of Underlying Etiologies
[186]
Cançado GGL, Deeb M, Gulamhusein AF. “Liver transplantation for cholestatic liver diseases: Timing and disease recurrence.” Hepatology (Baltimore, Md.) (2025). PMID: 39960305 ↗
L5REVIEW_NARRATIVECited in: Management of Underlying Etiologies
[187]
Guilabert L, Cárdenas-Jaén K, de-Madaria E. “Initial Management of Acute Pancreatitis.” Gastroenterology clinics of North America (2025). PMID: 39880529 ↗
L5REVIEW_NARRATIVECited in: Management of Underlying Etiologies
[188]
Masuda S, Imamura Y, Jinushi R et al.. “Navigating antibiotic therapy in acute cholangitis: Best practices and new insights.” Journal of hepato-biliary-pancreatic sciences (2025). PMID: 39537571 ↗
L5REVIEW_NARRATIVECited in: Management of Underlying Etiologies
[189]
Izumi H, Yoshii H, Fujino R et al.. “The usefulness of percutaneous bile duct metal stent insertion for malignant biliary obstruction: a retrospective study.” BMC gastroenterology (2025). PMID: 40165110 ↗
L3COHORTCited in: Management of Underlying Etiologies
[190]
Zhang X, Zhang L, Zhao S et al.. “Tumor marker pseudoprogression and immune-related cholangitis during conversion therapy for massive hepatocellular carcinoma: a case report.” Frontiers in immunology (2025). PMID: 40534866 ↗
L4CASE_REPORTCited in: Management of Underlying Etiologies
[191]
Khan R, Marchena-Romero KJ, Ismail MF et al.. “On-site ERCP availability and cholangitis outcomes: Retrospective cohort study.” Endoscopy international open (2025). PMID: 39958657 ↗
L3COHORTCited in: Management of Underlying Etiologies
[192]
Massironi S, Fanizzi F, Invernizzi F et al.. “Inflammatory bowel disease and primary sclerosing cholangitis: immunological links and clinical outlook.” Expert review of clinical immunology (2026). PMID: 42017751 ↗
L5REVIEW_NARRATIVECited in: Management of Underlying Etiologies
[193]
Zhang L, Huang J, Liu Q et al.. “Secondary choledocholithiasis caused by fish bones: a case report and review of the literature.” Journal of medical case reports (2025). PMID: 41327345 ↗
L4CASE_REPORTCited in: Management of Underlying Etiologies
[194]
Veyre F, Francoz C, Erard D et al.. “Graft and Patient Survival After Liver Transplantation for Primary Sclerosing Cholangitis: A French National Cohort Study.” Liver international : official journal of the International Association for the Study of the Liver (2026). PMID: 41816929 ↗
L3COHORTCited in: Complications and Long-term Outcomes
[195]
Ar E, Solomonidou I, Lenzen H et al.. “Long-term clinical and endoscopic outcomes of ulcerative colitis after liver transplantation: a multicenter cohort study on the use and safety of advanced therapies.” Inflammatory bowel diseases (2026). PMID: 41615920 ↗
L3COHORTCited in: Complications and Long-term Outcomes
[196]
D'Amico F, Allocca M, Lusetti F et al.. “Primary Sclerosing Cholangitis Worsens Prognosis in Patients With Inflammatory Bowel Disease: A Propensity-Matched Cohort Study.” United European gastroenterology journal (2025). PMID: 40920341 ↗
L3COHORTCited in: Complications and Long-term Outcomes
[197]
Liu F, Gu DJ, Pan J et al.. “Validation of the safety of primary laparoscopic common bile duct closure in acute cholangitis: a retrospective cohort study.” BMC surgery (2026). PMID: 41629855 ↗
L3COHORTCited in: Complications and Long-term Outcomes
[198]
Liu J, Song Y, Zhang D et al.. “Sex differences in the association between red cell distribution width and 30-day mortality in critically ill patients with acute cholangitis: a retrospective cohort study.” BMC gastroenterology (2025). PMID: 41419799 ↗
L3COHORTCited in: Complications and Long-term Outcomes
[199]
Afonso AB, da Silva CM, Nogueira P et al.. “Meta-Analysis: Comparison of Living Versus Deceased Liver Transplantation for Primary Sclerosing Cholangitis.” Alimentary pharmacology & therapeutics (2025). PMID: 40890931 ↗
L2SR_OBSCited in: Complications and Long-term Outcomes
[200]
Díaz-González Á, Molera C, Gómez-Domínguez E et al.. “Spanish clinical practice guidelines for the diagnosis and management of cholestatic liver diseases in adult and pediatric population: Joint report from AEEH and SEGHNP.” Gastroenterologia y hepatologia (2026). PMID: 41232665 ↗
L1GUIDELINECited in: Complications and Long-term Outcomes
[201]
Manes G, Paspatis G, Aabakken L et al.. “Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline.” Endoscopy (2019). PMID: 30943551 ↗
L1GUIDELINECited in: Landmark Evidence and Guideline Evolution
[202]
Miura F, Takada T, Strasberg SM et al.. “TG13 flowchart for the management of acute cholangitis and cholecystitis.” Journal of hepato-biliary-pancreatic sciences (2013). PMID: 23307003 ↗
L1GUIDELINECited in: Landmark Evidence and Guideline Evolution
[203]
Takada T, Strasberg SM, Solomkin JS et al.. “TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis.” Journal of hepato-biliary-pancreatic sciences (2013). PMID: 23307006 ↗
L1GUIDELINECited in: Landmark Evidence and Guideline Evolution
[204]
Itoi T, Tsuyuguchi T, Takada T et al.. “TG13 indications and techniques for biliary drainage in acute cholangitis (with videos).” Journal of hepato-biliary-pancreatic sciences (2013). PMID: 23307008 ↗
L1GUIDELINECited in: Landmark Evidence and Guideline Evolution
[205]
Okamoto K, Takada T, Strasberg SM et al.. “TG13 management bundles for acute cholangitis and cholecystitis.” Journal of hepato-biliary-pancreatic sciences (2013). PMID: 23307002 ↗
L1GUIDELINECited in: Landmark Evidence and Guideline Evolution
[206]
Gomi H, Solomkin JS, Takada T et al.. “TG13 antimicrobial therapy for acute cholangitis and cholecystitis.” Journal of hepato-biliary-pancreatic sciences (2013). PMID: 23340954 ↗
L1GUIDELINECited in: Landmark Evidence and Guideline Evolution
[207]
Kimura Y, Takada T, Kawarada Y et al.. “Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines.” Journal of hepato-biliary-pancreatic surgery (2007). PMID: 17252293 ↗
L1GUIDELINECited in: Landmark Evidence and Guideline Evolution