Primary sclerosing cholangitis (PSC) is a rare, progressive cholestatic disease of unknown etiology and characterized by inflammation and stricturing of intrahepatic and/or extrahepatic bile ducts. This process leads to bile duct scarring, progressive liver fibrosis, and end-stage liver disease. PSC is often associated with a specific form of inflammatory bowel disease and patients face a significant risk of developing cholangiocarcinoma and colorectal cancer. The clinical course of PSC can differ significantly between subtypes and affected individuals, representing a major obstacle to successful medical treatment trials. Numerous innovative therapeutic targets have been identified and, at least in part, explored, including nuclear and membrane receptors regulating bile acid metabolism and transport, modulation of gut microbiota, and signaling molecules involved in liver inflammation and fibrosis. Successful drug testing in preclinical PSC models as well as positive signals from some clinical studies justify hope. However, no medical treatment has so far been proven to improve transplant-free survival or overall survival in PSC patients. Disease-modifying drugs are urgently awaited. Despite ongoing efforts to improve study designs and implement treatment trials for novel drug targets, a central breakthrough has not yet been convincingly achieved. This situation might change in the near future. This article summarizes current research efforts aimed at developing medical treatments for PSC.

Primary sclerosing cholangitis (PSC) exhibits varying incidence and prevalence rates across different regions; however, comprehensive global studies examining its geographic distribution and future trends are scarce. This study presents an updated meta-analysis through 2024 and projects the global and regional prevalence of PSC from 2024 to 2040 using an illness-death multi-state model.

We conducted a thorough systematic search across multiple databases to identify all primary studies published until 2024 that reported on the incidence, prevalence, and mortality rates of PSC in various regions. Using the gathered data, we developed an illness-death model to forecast the future prevalence of PSC, covering the years 2024-2040.

Our meta-analysis revealed that the global pooled incidence and prevalence rates of PSC are 0.65 and 7.52 per 100,000 persons, respectively. Projections indicate that the global prevalence of PSC will rise to 22.98 cases per 100,000 (95% CI: 21.0-24.95), corresponding to an overall increase of 28.3%. Specifically, North America is forecasted to experience a 5.45% increase in PSC cases, reaching 24.76 cases per 100,000 (95% CI: 19.63-29.88), while Western Europe is anticipated to see a more pronounced rise of 28.79%, resulting in a prevalence of 21.48 cases per 100,000 (95% CI: 18.3-24.65) by 2040.

Our findings indicate a substantial rise in the number of individuals affected by PSC in recent years and estimate a significant future burden of the disease.

Primary sclerosing cholangitis (PSC) is associated with a high risk of hepatobiliary malignancy, especially cholangiocarcinoma (CCA). There are no good tumor markers to screen for CCA, and current recommendations for PSC monitoring are mainly based on expert opinions. The optimal strategy to assess disease progression and screen for CCA - the main cause of death of PSC patients - remains unclear. We aimed to compare three different surveillance strategies and their effect on patient outcomes.Data from three distinct PSC cohorts with different surveillance strategies - scheduled endoscopic retrograde cholangiopancreatography (ERCP), annual magnetic resonance imaging/cholangiopancreatography (MRI/MRCP) surveillance, and on-demand ERCP according to ESGE/EASL guidelines - was collected. Patients with PSC diagnosed in 1990 or later were included and the last day of follow-up was 31 December 2023. The composite end point consisted of hepatobiliary malignancy, liver transplantation, or liver-related death.1629 PSC patients were included, with a median follow-up of 8-11 years. The cumulative incidence of the composite end point was lowest in the group undergoing scheduled ERCP (14.1%, 95%CI 12.0%-16.4%) and highest in the on-demand ERCP cohort (35.0%, 95%CI 28.4%-42.0%). Although the cumulative incidence of CCA was lower in the scheduled ERCP group than in the other groups, it did not differ statistically significantly from the MRI/MRCP surveillance group. No differences were seen in liver-related deaths between the surveillance strategies.In this study comparing scheduled ERCP, annual MRI/MRCP surveillance, and on-demand ERCP, the strategy based on scheduled ERCP using individual risk stratification is associated with better overall prognosis and outcome.

Background/Objectives: Primary sclerosing cholangitis (PSC) is a rare, incurable liver disease characterized by chronic biliary inflammation and fibrosis. PSC is a significant risk factor for biliary tract cancer (BTC). This study aims to evaluate STAT3 expression in BTC and its prognostic significance as well as explore the potential of organoids derived from PSC and liver tumor patients as an in vitro model for testing novel therapeutic strategies in both PSC and BTC. Methods: Fresh tissue samples obtained from 10 PSC patients through targeted endoscopic retrograde cholangiography (ERC) and biopsy samples from liver tumor patients were used to establish organoid cultures. Organoids were treated with different agents and the therapeutic effect was measured by CellTiterGlo. Treatment with the JAK inhibitor baricitinib was followed by the measurement of cytokine concentrations in the supernatant. Archived formalin-fixed paraffin-embedded (FFPE) samples from 55 surgically resected BTC tumors were analyzed for STAT3 expression using immunohistochemistry. Results: We successfully established organoid cultures from all ERC samples. STAT3 protein expression was detected in 56% of tumor samples and 69% of the immune microenvironment. STAT3 positivity in the immune cell compartment was associated with longer disease-free survival, although the multivariate analysis could not confirm its value as an independent prognostic factor. Chemotherapy testing on liver tumor organoids showed various degrees of decreases in viability after treatment with gemcitabine, cisplatin, and cabozantinib. Baricitinib treatment significantly reduced IL-6 and MCP-1 secretion in cholangiocarcinoma Conclusions: The patient-derived organoid model of PSC and liver tumors is a valuable tool for testing novel and established therapeutic strategies, including JAK inhibitors and chemotherapy regimens. STAT3 expression in the immune microenvironment of BTC may serve as a prognostic marker. Further studies are needed to explore the integration of co-cultured organoid systems with stromal and immune components to improve physiological relevance.

Our purpose was to evaluate the performance of MR imaging/cholangiography for ductal cholangiocarcinoma (CCA) diagnosis and to search for specific MR features of ductal CCA among primary sclerosing cholangitis (PSC) patients.

We retrospectively analyzed 31 patients from a single center, each with a diagnosis of PSC, and suspicion of ductal CCA. Ductal CCA had been suspected during multidisciplinary team meetings when high-grade biliary stenosis was associated with focal thickening of the biliary wall. Two radiologists blinded to clinical information and imaging history independently reviewed patients' MR examinations using a standardized model created for this study. Fisher's exact test and Student's t-test were used to analyze the population's characteristics. Fisher's exact test and the chi-square test were used to compare associations of categorical variables (each standard model's item) with the final diagnosis. Interobserver agreement was assessed by Cohen's κ coefficient.

Our population had a mean age of 42.7 ± 13.6 years and included 68% males. The final diagnosis was ductal CCA for 14 patients, and inflammatory stenosis for 17 patients. For diagnosing CCA, MR imaging/cholangiography exhibited a sensitivity of 43-50% and specificity of 70-76%, with low positive predictive (58-60%) and negative predictive (62-63%) values. Interobserver agreement ranged from κ = 0.04-0.75. Univariate analysis revealed no significant association between individual MR imaging/cholangiography features and CCA diagnosis.

MR imaging/cholangiography showed suboptimal performance for ductal CCA diagnosis among PSC patients and we did not find any specific feature to distinguish ductal CCA from inflammatory stenosis.

Question Diagnosing ductal cholangiocarcinoma in patients with primary sclerosing cholangitis remains challenging without known predictive MR imaging features. Findings MR imaging/cholangiography exhibited low sensitivity, specificity, and interobserver reliability for ductal cholangiocarcinoma diagnosis in primary sclerosing cholangitis and lacks reliability for distinguishing between benign and malignant strictures. Clinical relevance Diagnosing ductal cholangiocarcinoma in patients with primary sclerosing cholangitis remains challenging and our retrospective study demonstrates that MR imaging lacks reliability in distinguishing between benign and malignant high-grade strictures and did not find any specific MR feature of ductal CCA.

The three major autoimmune liver diseases are autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC).These conditions are assumed to result from a breakdown in immunological tolerance, which leads to an inflammatory process that causes liver damage.The self-attack is started by T-helper cell-mediated identification of liver autoantigens and B-cell production of autoantibodies,and it is maintained by a reduction in the number and activity of regulatory T-cells.Infections and environmental factors have been explored as triggering factors for these conditions, in addition to a genetic predisposition.Allelic mutations in the HLA locus have been linked to vulnerability, as have relationships with single nucleotide polymorphisms in non-HLA genes.Despite the advances in the management of these diseases, there is no curative treatment for these disorders, and a significant number of patients eventually progress to an end-stage liver disease requiring liver transplantation.In this line, tailored immune-therapeutics have emerged as possible treatments to control the disease.In addition, early diagnosis and treatment are pivotal for reducing the long-lasting effects of these conditions and their burden on quality of life.Herein we present a review of the etiology, clinical presentation, diagnosis, and challenges on ALDs and the feasible solutions for these complex diseases.

Liver transplantation is essential for many people with primary sclerosing cholangitis (PSC). People with PSC are less likely to receive a deceased donor liver transplant compared with other causes of chronic liver disease. This disparity may stem from the inaccuracy of the model for end-stage liver disease (MELD) in predicting waitlist mortality or dropout for PSC. The broad applicability of MELD across many causes comes at the expense of accuracy in prediction for certain causes that involve unique comorbidities. We aimed to develop a model that could more accurately predict dynamic changes in waitlist outcomes among patients with PSC while including complex clinical variables.

We developed 3 machine learning architectures using data from 4666 patients with PSC in the Scientific Registry of Transplant Recipients (SRTR) and tested our models on our institutional data set of 144 patients at the University Health Network (UHN). We evaluated their time-dependent concordance index (C-index) for mortality prediction and compared it against MELD-sodium and MELD 3.0.

Random survival forest (RSF), a decision tree-based survival model, outperformed MELD-sodium and MELD 3.0 in both the SRTR and the UHN test data set using the same bloodwork variables and readily available demographic data. It achieved a C-index of 0.868 (SD 0.020) and 0.771 (SD 0.085) on the SRTR and UHN test data, respectively. Training a separate RSF model using the UHN data with PSC-specific achieved a C-index of 0.91. In addition to high MELD score, increased white blood cells, time on the waiting list, platelet count, presence of Autoimmune hepatitis-PSC overlap, aspartate aminotransferase, female sex, age, history of stricture dilation, and extremes of body weight were the top-ranked features predictive of the outcomes.

Our RSF model offers more accurate waitlist outcome prediction in PSC. The significant performance improvement with the inclusion of PSC-specific variables highlights the importance of disease-specific variables for predicting trajectories of clinically distinct presentations.

Patients with primary sclerosing cholangitis (PSC) are at increased risk of acute cholangitis. The epidemiological risks of cholangitis are poorly studied despite the high morbidity associated with this infection. The aim of this study was to understand the impact of statins on acute cholangitis in PSC.

This multicenter, retrospective cohort study assessed data from 294 patients with PSC at Stanford Medical Center, Baylor Medical Center, and Valley Medical Center. Clinical factors associated with the development of cholangitis were identified using multivariable Cox regression.

The patients were predominantly male (68.7%) with a median age at enrollment of 48 years (interquartile range [IQR]: 31.0-60.8). Fifty patients (17.0%) were prescribed statins. The median follow-up time was 6 years (IQR: 2.0-12.0), in which 29.6% (n = 87) developed cholangitis. In multivariable analysis, statins were associated with an 81% reduction in cholangitis (HR 0.19, 95% confidence interval 0.03-0.64). Statins were associated with a lower adjusted incidence of cholangitis at 36 months compared with patients not on statin therapy (incidence of 2.8% vs 12.2%, P < 0.001). Statins were also associated with increased time-to-stricture ( P = 0.004), an outcome known to be associated with PSC complications.

Statin therapy is associated with reduced risk of cholangitis in PSC, possibly by delaying the time to develop dominant or high-grade strictures. In patients with PSC, use of statin therapy may be a beneficial modality to prevent the development of cholangitis and warrants further investigation.

The main cholestatic liver diseases comprise primary sclerosing cholangitis, primary biliary cholangitis, and IgG4-related cholangitis. Despite being classified as rare diseases, these are becoming gradually more important in the field of hepatology since their incidence is slowly rising while the viral hepatitis burden is declining. Cholestatic liver diseases now rank among the 3 most frequent indications for liver transplantation in many Western countries. An accurate understanding of the epidemiology and burden of disease on both the individual and society of cholestatic diseases is of great importance. This review aims to provide a comprehensive overview of the current literature on the epidemiology, health-related quality of life, and economic burden of primary sclerosing cholangitis, primary biliary cholangitis, and IgG4-related cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic liver disease characterised by inflammation and fibrosis of the bile ducts, conferring an increased risk of cholangiocarcinoma (CCA). However, detecting CCA early in PSC patients remains challenging due to the limited sensitivity of conventional diagnostic methods, including imaging or bile duct brush cytology during endoscopic retrograde cholangiopancreatography (ERCP). This study aims to evaluate the potential of bile cell-free DNA (cfDNA) mutational analysis, termed the Bilemut assay, as a tool for CCA detection in PSC patients.

Sixty-three PSC patients undergoing ERCP due to biliary strictures were prospectively recruited. Bile samples were collected, and cfDNA was extracted and analysed using the Oncomine Pan-Cancer Cell-Free assay. Twenty healthy liver donors were included for comparison. Samples with a mutant allele frequency (MAF) ≥ 0.1% were considered positive. Correlations between mutational status and clinical characteristics were assessed.

cfDNA mutational analysis was successful in all bile samples. Mutations predominantly in KRAS, GNAS, and TP53 were detected in 36.5% (23/63) of PSC patients, compared to 10% (2/20) of healthy donors (p = 0.0269). The clinical characteristics of Bilemut-positive and -negative patients were comparable, though there was a trend towards a lower prevalence of inflammatory bowel disease in the Bilemut-positive group. Among PSC patients diagnosed with CCA during follow-up, 75% were Bilemut-positive, suggesting an association between mutational status and malignancy risk.

Mutational analysis of cfDNA obtained from bile collected from PSC patients undergoing ERCP is feasible. Implementing the Bilemut assay may help identify patients needing closer surveillance and further imaging studies.

CCA is a highly desmoplastic malignant cancer and is the second most common primary liver malignancy after hepatocellular carcinoma (HCC), accounting for approximately 15% of all primary liver tumors. CCA has a poor prognosis, with an average five-year survival rate of 9%, which is lower than that of pancreatic cancer. Although considerable efforts have been invested into the genomics, epigenetics, and risk factors, very little is known about what might have been the key causes for the high malignancy level of CCA. In this review, we analyze the incidence and mortality of CCA in different regions based on data from 1994 to 2022 obtained from the International Agency for Research on Cancer (IARC), discuss the current status of treatment of the disease, and focus on what might be the main factors contributing to the high malignancy level of CCA: alkalosis caused by the Fenton reaction, hypoxia, and the TIME. The review includes studies published from 1979 to 2024, aiming to provide an updated synthesis of basic early classical theoretical knowledge and current knowledge about CCA. By revealing the epidemiological characteristics of CCA, the potential mechanisms of high malignancy, and the current challenges of treatment, this review aims to provide new directions for future cancer research, promote the development of personalized treatment strategies, and facilitate a deeper understanding and the more effective management of CCA worldwide.

Background: The Mayo Risk Score (MRS) predicts short-term mortality in primary sclerosing cholangitis (PSC) using the age, bilirubin, albumin, aspartate aminotransferase (AST), and variceal bleeding history. While the MRS has been validated in end-stage PSC, its ability to predict liver transplantation (LT) and outcomes in newly diagnosed patients without advanced disease remains unclear. This study evaluated the effectiveness of the MRS in predicting LT and mortality in this patient population. Methods: We analyzed data from 109 adults with PSC enrolled in a prospective registry (2018-2024) with ≥4 years of follow-up. Logistic regression identified the predictors of LT or death, and the model performance was assessed using the area under the receiver operating characteristic curve (AUROC). Multicollinearity was evaluated using the variance inflation factor (VIF). Results: Among the 109 patients (mean age 45 ± 15 years, 51% female), 85% remained alive without LT, 12% underwent LT, and 3% died over a median follow-up of 4.63 years. The MRS was significantly associated with LT or death (OR 3.08, p < 0.001) and demonstrated excellent predictive performance (AUROC 0.99, p < 0.001). The model achieved 95.45% sensitivity, 98.85% specificity, and a correct classification rate of 98.17%, supporting its clinical utility. Conclusion: The MRS is a robust tool for risk stratification in PSC, predicting LT and mortality. These findings highlight its broader applicability beyond end-stage PSC and underscore its potential for guiding clinical management and early intervention strategies.

Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic disease that can progress to cirrhosis and liver failure. The natural history of PSC is variable as liver enzymes and liver symptoms fluctuate over time. Several drugs for PSC are under investigation, but there are currently no economic models to evaluate the cost-effectiveness and value of new treatments. The objective of this study was to develop an early economic model for PSC and validate the natural history component.

A lifetime horizon Markov cohort model was developed to track the progression of adults with PSC with or without inflammatory bowel disease. Based on relevant literature and clinical expert advice, fibrosis staging was used to model disease progression. Evidence on disease progression, mortality, PSC-related complications, and secondary cancers was identified by literature searches and validated by interviews with clinical and cost-effectiveness modelling experts. Model outcomes were overall survival and transplant-free survival years, and the proportions of patients receiving liver transplants, 2nd liver transplants after recurrent PSC (rPSC), and developing rPSC after liver transplantation during their lifetime. Cumulative incidence of secondary cancers and quality-adjusted life-years (QALYs) were also tracked.

Model outcomes are in line with estimates reported in literature recommended by clinical experts. Overall survival (95% uncertainty interval [UI]) was estimated to be 25.0 (23.2-26.3) years and transplant-free survival was estimated to be 22.0 (20.2-23.6) years. The estimated proportion (95% UI) of patients receiving first liver transplants was 14.5% (11.6-17.1%), while the proportion of patients developing rPSC and receiving 2nd liver transplants after rPSC was 24.2% (20.4-28.0%) and 21.6% (12.9-29.7%), respectively. The cumulative incidence (95% UI) of cholangiocarcinoma, colorectal cancer, and gallbladder cancer were estimated at 5.2% (2.1-10.0%), 3.6% (1.4-5.4%), and 3.3% (1.2-7.6%), respectively. Discounted lifetime QALYs per patient (95% UI) were estimated at 16.4 (15.6-17.1).

We have developed a model framework to simulate the progression of PSC with estimates of overall and transplant-free survival. This model, which calibrates well with existing estimates of disease progression, may be useful to evaluate the clinical and economic benefits of future treatments.

Primary sclerosing cholangitis (PSC) is a chronic biliary inflammation associated with periductular fibrosis of the intrahepatic and extrahepatic bile ducts leading to strictures, bacterial cholangitis, decompensated liver disease and need for liver transplantation. This rare focal liver disease affects all races and ages, with a predominance of young males. There is an up to 88% association with inflammatory bowel disease. Although the aetiology is unknown and the pathophysiology is poorly understood, PSC is regarded as an autoimmune liver disease based on a strong immunogenetic background. Further, the associated risk for various malignancies, particularly cholangiocellular carcinoma, is also poorly understood. No medical therapy has been approved so far nor has been shown to improve transplant-free survival. However, ursodeoxycholic acid is widely used since it improves the biochemical parameters of cholestasis and is safe at low doses. MRI of the biliary tract is the primary imaging technology for diagnosis. Endoscopic interventions of the bile ducts should be limited to clinically relevant strictures for balloon dilatation, biopsy and brush cytology. End-stage liver disease with decompensation is an indication for liver transplantation with recurrent PSC in up to 38% of patients. Several novel therapeutic strategies are in various stages of development, including apical sodium-dependent bile acid transporter and ileal bile acid transporter inhibitors, integrin inhibitors, peroxisome proliferator-activated receptor agonists, CCL24 blockers, recombinant FGF19, CCR2/CCR5 inhibitors, farnesoid X receptor bile acid receptor agonists, and nor-ursodeoxycholic acid. Manipulation of the gut microbiome includes faecal microbiota transplantation. This article summarizes present knowledge and defines unmet medical needs to improve quality of life and survival.

Primary sclerosing cholangitis (PSC) is a rare immune-mediated hepatobiliary disease, characterised by progressive biliary fibrosis, cirrhosis, and end-stage liver disease. As yet, no licensed pharmacological therapy exists. While significant advancements have been made in our understanding of the pathophysiology, the exact aetiology remains poorly defined. Compelling evidence from basic science and translational studies implicates the role of T helper 17 cells (Th17) and the interleukin 17 (IL-17) pro-inflammatory signalling pathway in the pathogenesis of PSC. However, exploration of the safety and efficacy of inhibiting the IL-17 pathway in PSC is lacking.

This is a phase 2a, open-label, multicentre pilot study, testing the safety of brodalumab, a recombinant human monoclonal antibody that binds with high affinity to interleukin-17RA, in adults with PSC. This study will enrol 20 PSC patients across five large National Health Service tertiary centres in the UK. The primary outcome of the study relates to determining the safety and feasibility of administering brodalumab in early, non-cirrhotic PSC patients. Secondary efficacy outcomes include non-invasive assessment of liver fibrosis, changes in alkaline phosphatase values and other liver biochemical readouts, assessment of biliary metrics through quantitative MR cholangiography+, and quality of life evaluation on completion of follow-up (using the 5D-itch tool, the PSC-patient-reported outcome and PSC-specific Chronic Liver Disease Questionnaire).

Ethical approval for this study has been obtained from the London Bridge Research Ethics Committee (REC23/LO/0718). Written informed consent will be obtained from all trial participants prior to undertaking any trial-specific examinations or investigations. On completion of the study, results will be submitted for publication in peer-reviewed journals and presented at national and international hepatology meetings. A summary of the findings will also be shared with participants and PSC communities.

ISRCTN15271834.

Cholestasis, characterized by impaired bile flow, is associated with an increased risk of cholangiocarcinoma (CCA), a malignancy originating from the biliary epithelium and hepatocytes. Hepatic nuclear receptors (NRs) are pivotal in regulating bile acid and metabolic homeostasis, and their dysregulation is implicated in cholestatic liver diseases and the progression of liver cancer. This review elucidates the role of various hepatic NRs in the pathogenesis of cholestasis-to-CCA progression. It explores their impact on bile acid metabolism as well as their interactions with other signaling pathways implicated in CCA development. Additionally, it introduces available murine models of cholestasis/primary sclerosing cholangitis leading to CCA and discusses the clinical potential of targeting hepatic NRs as a promising approach for the prevention and treatment of cholestatic liver diseases and CCA. Understanding the complex interplay between hepatic NRs and cholestasis-to-CCA pathology holds promise for the development of novel preventive and therapeutic strategies for this devastating disease.

Benign tumors of the liver and biliary tract are rare entities, and some of them require surgical management to prevent their malignant transformation. Tumors from the biliary tract with malignant potential are treated either by hepatic resection, for mucinous cystic neoplasm and ciliated hepatic foregut cysts, or by biliary resections, for biliary papillary neoplasm and type I and IV choledochal cysts. The pathologies requiring prophylactic cholecystectomy are polyps larger than 10 mm, porcelain gallbladder and pancreaticobiliary maljunction. Finally, hepatocellular adenoma over 5cm, occurring in male patients, or exon 3 mutated beta-catenin, should lead to prophylactic resection by hepatic segmentectomy. This article describes these different pathologies and their management.

Cholangiocarcinoma (CCA) is a rare but highly malignant carcinoma of bile duct epithelial cells with a poor prognosis. The major risk factors of CCA carcinogenesis and progression are cholestatic liver diseases. The key feature of primary sclerosing cholangitis and primary biliary cholangitis is chronic cholestasis. It indicates a slowdown of hepatocyte secretion of biliary lipids and metabolites into bile as well as a slowdown of enterohepatic circulation (bile acid recirculation) of bile acids with dysbiosis of the gut microbiome. This leads to enterohepatic recirculation and an increase of toxic secondary bile acids. Alterations of serum and liver bile acid compositions via the disturbed enterohepatic circulation of bile acids and the disturbance of the gut microbiome then activate a series of hepatic and cancer cell signaling pathways that promote CCA carcinogenesis and progression. This review focuses on the mechanistic roles of bile acids and the gut microbiome in the pathogenesis and progression of CCA. It also evaluates the therapeutic potential of targeting the gut microbiome and bile acid-mediated signaling pathways for the therapy and prophylaxis of CCA.

Biliary brushing cytology (BB) to detect cholangiocarcinoma (CCA) is integral in the surveillance of patients with primary sclerosing cholangitis (PSC). Since reactive changes can mimic carcinoma, indeterminant results are frequent. Fluorescence in situ hybridization (FISH) using the UroVysion probe set has been advocated to enhance the detection of CCA. This study evaluates the performance of FISH for detecting CCA in patients with and without PSC.

A query of our pathology database for atypical and suspicious BB with concurrent FISH results was performed from 2014 to 2021. FISH (using UroVysion probe set containing centromere enumeration probes to chromosomes 3, 7, and 17) was positive if at least 5 cells demonstrated polysomy. Electronic medical records were reviewed to identify patients with PSC and CCA. CCA was confirmed by pathology or clinical impression.

Of the 65 patients (103 BB) in the PSC cohort, 59 patients (94 BB) without CCA and 6 patients (9 BB) with CCA were identified. 33 non-PSC patients (41 BB) with CCA were included for comparison. Positive FISH was highest in non-PSC patients with CCA (10/41 BB, 24%). Positive FISH was seen in both PSC with (1/9 BB, 11%) and without (2/94 BB, 2%) CCA.

FISH positivity was lower than expected and was positive in PSC patients without CCA. These results question the clinical utility of FISH for CCA surveillance in PSC patients.

Primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma. When a child is diagnosed with both PSC and inflammatory bowel disease (IBD), evidence-based information on counseling families and risk management of developing cholangiocarcinoma is limited. In this case series (PubMed/collaborators), we included patients with PSC-IBD who developed cholangiocarcinoma and contacted authors to determine an event curve specifying the time between the second diagnosis (IBD or PSC) and a diagnosis of cholangiocarcinoma. Review of n = 175 studies resulted in a cohort of n = 21 patients with pediatric-onset PSC-IBD-cholangiocarcinoma. The median time to development of cholangiocarcinoma was 6.95 years from the second diagnosis. Despite the small number, 38% of cholangiocarcinoma developed within the first 2 years, and 47% of patients developed cholangiocarcinoma in the transition period to adult care (age 14-25). Our findings highlight the importance of screening that extends over the so-called transition period from pediatric to adult care.

Sclerosing cholangitis is a rare progressive cholestatic disease that is classified as secondary sclerosing cholangitis when it is caused by an identifiable cause. Sclerosing cholangitis has been linked to infections like COVID-19 and parasitic infections like Clonorchis sinensis and Ascaris lumbricoides. However, leptospirosis has not been linked to sclerosing cholangitis in the medical literature. In this article, we report a 37-year-old gentleman who was diagnosed with leptospirosis, worsened by painless cholestasis, while he was improving from leptospirosis. Magnetic resonance cholangiopancreatography revealed multiple short-segment biliary strictures, segmental dilatation, and mural irregularities in both intrahepatic ducts confirming the diagnosis of sclerosing cholangitis. After ruling out other potential causes and considering the initial presentation during a leptospirosis infection, we concluded that leptospirosis caused secondary sclerosing cholangitis. We report this as the first case of secondary sclerosing cholangitis in a leptospirosis patient without renal, respiratory, or cardiac complications, emphasizing the importance of ruling out this cause in a leptospirosis patient with persistent cholestasis.

As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.

Epidemiological data on mortality in autoimmune liver diseases (AILDs) are scarce. We examined all-cause and cancer-related mortality in individuals with AILD from Sweden.

We identified 9654 individuals with AILD (3342 with autoimmune hepatitis (AIH), 3751 with primary biliary cholangitis (PBC), and 2561 with primary sclerosing cholangitis (PSC)) using national Swedish registries between 2001 and 2020. These were matched with 80 685 comparators from the general population at a ratio of 1:10 on age, sex, year of diagnosis and municipality. Rates of outcomes were estimated using Cox regression models, adjusted for matching factors and cardiovascular disease, diabetes, inflammatory bowel disease, chronic obstructive pulmonary disease, and education.

Individuals with AILD had higher mortality than comparators (adjusted hazard ratio (aHR) = 2.3, 95% CI = 2.2-2.4) and higher rates of cancer-related death (aHR = 2.1, 95% CI = 1.9-2.3). The presence of liver cirrhosis in AILD was related to even higher mortality, with aHR 5.8 (95% CI = 5.1-6.6). Both males and females with AILD had increased mortality (males aHR = 2.6, 95% CI = 2.4-3.0, and females aHR = 2.2, 95% CI = 2.1-2.3). The mortality was higher in individuals aged 18-50 years (aHR = 4.6, 95% CI = 3.6-5.8), than in individuals above 50 years (aHR = 2.2, 95% CI = 2.1-2.3). Overall mortality rates and cancer-related death were particularly high in individuals with PSC compared to their matched comparators, with aHR = 4.1 (95% CI = 3.2-5.2) and aHR = 6.4 (95% CI = 4.0-10.3), respectively.

Patients with AILDs have increased rates of overall and cancer-related mortality compared to matched comparators, and relative risks are highest in cirrhosis, younger age and PSC.

We aimed to provide an evidence-supported approach to diagnose, monitor, and treat children with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC).

The core group formulated seven PICO-structured clinical questions. A systematic literature search from inception to December 2022 was conducted by a medical librarian using MEDLINE and EMBASE. Core messages from the literature were phrased as position statements and then circulated to a sounding board composed of international experts in pediatric gastroenterology and hepatology, histopathology, adult gastroenterology and hepatology, radiology, and surgery. Statements reaching at least 80% agreement were considered as final. The other statements were refined and then subjected to a second online vote or rejection.

Regular screening for gamma-glutamyltransferase (GGT) is essential for detecting possible biliary disease in children with IBD. MR cholangiopancreatography is the radiological modality of choice for establishing the diagnosis of PSC. Liver biopsy is relevant in the evaluation of small duct PSC or autoimmune hepatitis. Children who do not have known IBD at the time of PSC diagnosis should undergo initial screening with fecal calprotectin for asymptomatic colitis, and then at least once yearly thereafter. Children with a cholestatic liver enzyme profile can be considered for treatment with ursodeoxycholic acid and can continue if there is a meaningful reduction or normalization in GGT. Oral vancomycin may have a beneficial effect on GGT and intestinal inflammation, but judicious use is recommended due to the lack of long-term studies. Children with PSC-IBD combined with convincing features of autoimmune hepatitis may benefit from corticosteroids and antimetabolites.

We present state-of-the-art guidance on the diagnostic criteria, follow-up strategies, and therapeutic strategies and point out research gaps in children and adolescents with PSC-IBD.

This meta-analysis aimed to evaluating the prevalence of Crohn's disease in primary sclerosing cholangitis (PSC) and the incidence of primary sclerosing cholangitis in Crohn's disease (CD), along with their interrelation.

An extensive search was conducted in the PubMed and Embase to identify available publications up to December 2023. Studies were included if they reported the prevalence of CD in PSC patients, or vice versa. Proportions were assessed using the DerSimonian and Laird method, followed by transformation via the Freeman-Tukey double inverse sine transformation. The quality of the included studies utilizing the Joanna Briggs Institute Critical Appraisal Checklist.

Based on quantitative analysis of 61 studies, the prevalence of PSC in patients with CD was 0.88% (95% CI: 0.53-1.30%). The prevalence of PSC in male CD patients was 0.45% (95% CI: 0.03-1.16%). In female CD patients, the prevalence was 0.51% (95% CI: 0.09-1.14%). The prevalence of CD with PSC was 11.27% (95% CI: 9.56-13.10%). The prevalence of CD in male PSC patients was 10.71% (95% CI: 7.42-14.50%). Among female PSC patients, the pooled prevalence of CD was 13.05% (95% CI: 11.05-15.19%).

We found a significant bidirectional association between PSC and CD, with a higher prevalence of CD in female with PSC compared to male. These findings provide important epidemiological data for clinical practice.

The clinical characteristics of de novo inflammatory bowel disease (dnIBD) diagnosed after solid organ transplant (SOT) are not well-described, particularly since the advent of biologic therapy for treatment of IBD.

We conducted a single-center, retrospective review of SOT recipients between 2010 and 2022 at the University of Minnesota Medical Center who were diagnosed with IBD after transplant.

Of 89 patients at our center with IBD and a history of SOT, five (5.6%) patients were diagnosed with IBD post-transplant (three liver, one kidney, and one simultaneous liver and kidney): three patients were female and four were Caucasian. Mean age at transplant and IBD diagnosis were 46.7 and 49.4 years respectively. Indication for transplant were alcohol-related cirrhosis (n = 2), idiopathic fulminant hepatic failure (n = 1), metabolic dysfunction-associated steatotic liver disease (n = 1), and IgA nephropathy (n = 1). Four patients were diagnosed with ulcerative colitis (UC) and one with Crohn's disease (CD). Three patients (all with UC) required escalation to a biologic therapy. Four patients were in clinical remission from IBD at last follow-up, one patient required IBD surgery, while there was no rejection and no deaths following IBD diagnosis.

dnIBD post-SOT is uncommon, while newer IBD therapies may be safe and effective. Further study is required to better understand the natural history and IBD outcomes of this population relative to non-SOT patients.

Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity. However, the longevity of such changes and the impact on markers of disease activity and disease progression have not been studied. The aim of this clinical trial is to determine the effects of repeated FMT as a treatment for PSC-IBD.

FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO) is a phase IIa randomised placebo-controlled trial to assess the efficacy and safety of repeated colonic administration of FMT in patients with non-cirrhotic PSC-IBD. Fifty-eight patients will be recruited from six sites across England and randomised in a 1:1 ratio between active FMT or FMT placebo arms. FMT will be manufactured by the University of Birmingham Microbiome Treatment Centre, using stool collected from rigorously screened healthy donors. A total of 8 weekly treatments will be delivered; the first through colonoscopic administration (week 1) and the remaining seven via once-weekly enema (up to week 8). Participants will then be followed on a 12-weekly basis until week 48 from the first treatment visit. The primary efficacy outcome will be to determine the effect of FMT on serum alkaline phosphatase values over time (end of study at 48 weeks). Key secondary outcomes will be to evaluate the impact of FMT on other liver biochemical parameters, PSC risk scores, circulating and imaging markers of liver fibrosis, health-related quality of life measures, IBD activity and the incidence of PSC-related clinical events. Key translational objectives will be to identify mucosal metagenomic, metatranscriptomic, metabolomic and immunological pathways associated with the administration of FMT.

The protocol was approved by the South Central-Hampshire B Research Ethics Committee (REC 23/SC/0147). Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

The trial was registered at ClinicalTrials.gov on 23 February 2024 (NCT06286709). Weblink: Study Details | FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis | ClinicalTrials.gov.

Cholangiocarcinoma (CCA) is a dreaded complication of primary sclerosing cholangitis (PSC) that is difficult to diagnose and associated with high mortality. A lack of animal models of CCA recapitulating the hepatic microenvironment of sclerosing cholangitis has hindered the development of novel treatments. Herein, we sought to develop a mouse model of PSC-associated CCA.

Ten-week-old Mdr2-/- mice with congenital PSC-like disease, and healthy wild-type littermates were subjected to either modified retrograde biliary instillation or hydrodynamic tail vein injection of a sleeping beauty transposon-transposase plasmid system with activated AKT (myr-AKT) and Yap (YapS127A) proto-oncogenes (SB AKT/YAP1). The role of TGFβ was interrogated via ALK5 inhibitor (SB-525334) administration. Tumor phenotype, burden and desmoplastic reaction were analyzed histologically and via RNA sequencing.

While SB AKT/YAP1 plasmids administered via retrograde biliary injection caused tumors in Mdr2-/-, only 26.67% (4/15) of these tumors were CCA. Alternatively, hydrodynamic tail vein injection of SB AKT/YAP1 resulted in robust tumorigenesis in all fibrotic Mdr2-/- mice with high CCA burden compared to healthy mice. Tumors phenotypically resembled human CCA, expressed multiple CCA (but not hepatocellular carcinoma) markers, and exhibited a profound desmoplastic reaction. RNA sequencing analysis revealed profound transcriptional changes in CCA evolving in a PSC-like context, with specific alterations in multiple immune pathways. Pharmacological TGFβ inhibition led to enhanced immune cell tumor infiltration, reduced tumor burden and suppressed desmoplastic collagen accumulation compared to placebo.

We established a new high-fidelity cholangiocarcinoma model in mice, termed SB CCA.Mdr2-/-, which recapitulates the increased susceptibility to CCA in the setting of biliary injury and fibrosis observed in PSC. Through transcriptomics and pharmacological studies, we show dysregulation of multiple immune pathways and TGFβ signaling as potential drivers of CCA in a PSC-like microenvironment.

Animal models for primary sclerosing cholangitis (PSC)-related cholangiocarcinoma (PSC-CCA) are lacking. Thus, we have developed and characterized a new mouse model of PSC-CCA, termed SB CCA.Mdr2-/-, which features reliable tumor induction on a PSC-like background of biliary injury and fibrosis. Global gene expression alterations were identified and standardized tools, including automated whole slide image analysis methodology for tumor burden and feature analysis, were established to enable systematic research into PSC-CCA biology and formal preclinical drug testing.

Primary sclerosing cholangitis (PSC) is a known risk factor for hepatobiliary malignancies. We conducted a systematic review and meta-analysis of published studies to determine the incidence and risk factors for hepatobiliary malignancies in people with PSC.

Pubmed and Embase databases were searched from inception to April 10, 2024, for cohort studies reporting data on the incidence of cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), or gallbladder cancer (GBC) in PSC. Pooled incidence rates with 95% confidence intervals (CIs) were estimated using a random effects model.

We identified 51 eligible studies involving 26,482 patients. The total follow-up was 221,258.1 person-years (PYs). The pooled incidence rates for overall PSC were 9.31 (95% CI, 6.84-12.67; I2 = 74%), 1.73 (95% CI, 1.20-2.51; I2 = 55%), and 1.06 (95% CI, 0.85-1.31; I2 = 0%) per 1000 PYs for CCA, HCC, and GBC, respectively. In patients with PSC with inflammatory bowel disease (IBD), rates were 7.16 (95% CI, 4.48-11.44; I2 = 96%), 2.19 (95% CI, 1.48-3.25; I2 = 58%), and 1.52 (95% CI, 1.21-1.90; I2 = 0%) per 1000 PYs, respectively. Subgroup analysis showed that the incidence of CCA was higher in smaller studies (<200 patients), and the incidence of HCC varied significantly by region (P = .03), with Oceania having the highest incidence and Europe having the lowest. Meta-regression determined that PSC-IBD was associated with HCC incidence.

The incidence of CCA in PSC is substantial, whereas HCC and GBC are rare. Patients with PSC-IBD may be at higher risk for HCC. These data should be validated in large, prospective studies, and may guide the development of evidence-based surveillance strategies for hepatobiliary malignancies in PSC.

Biliary obstruction and cholangiocyte hyperproliferation are important features of cholangiopathies affecting the large extrahepatic bile duct (EHBD). The mechanisms underlying obstruction-induced cholangiocyte proliferation in the EHBD remain poorly understood. Developmental pathways, including WNT signaling, are implicated in regulating injury responses in many tissues, including the liver. To investigate the contribution of WNT signaling to obstruction-induced cholangiocyte proliferation in the EHBD, we used complementary in vivo and in vitro models with pharmacologic interventions and transcriptomic analyses. To model obstruction, we used bile duct ligation (BDL) in mice. Human and mouse biliary organoids and mouse biliary explants were used to investigate the effects of WNT activation and inhibition in vitro. We observed an upregulation of WNT ligand expression associated with increased biliary proliferation following obstruction. Cholangiocytes were identified as both WNT ligand-expressing and WNT-responsive cells. Inhibition of WNT signaling decreased cholangiocyte proliferation in vivo and in vitro, while activation increased proliferation. WNT effects on cholangiocyte proliferation were β-catenin dependent, and we showed a direct effect of WNT7B on cholangiocyte growth. Our studies suggested that cholangiocyte-derived WNT ligands can activate WNT signaling to induce proliferation after obstructive injury. These findings implicate the WNT pathway in injury-induced cholangiocyte proliferation within the EHBD.

Chronic liver disease is a major cause of morbidity and mortality worldwide. Epidemiology, clinical phenotype and response to therapies for gastrointestinal and liver diseases are commonly different between women and men due to sex-specific hormonal, genetic and immune-related factors. The hepatic immune system has unique regulatory functions that promote the induction of intrahepatic tolerance, which is key for maintaining liver health and homeostasis. In liver diseases, hepatic immune alterations are increasingly recognized as a main cofactor responsible for the development and progression of chronic liver injury and fibrosis. In this Review, we discuss the basic mechanisms of sex disparity in hepatic immune regulation and how these mechanisms influence and modify the development of autoimmune liver diseases, genetic liver diseases, portal hypertension and inflammation in chronic liver disease. Alterations in gut microbiota and their crosstalk with the hepatic immune system might affect the progression of liver disease in a sex-specific manner, creating potential opportunities for novel diagnostic and therapeutic approaches to be evaluated in clinical trials. Finally, we identify and propose areas for future basic, translational and clinical research that will advance our understanding of sex disparities in hepatic immunity and liver disease.

To analyze the role of qualitative and quantitative 3 T MR imaging assessment as a non-invasive method for the evaluation of disease severity in patients with primary sclerosing cholangitis (PSC).

A series of 26 patients, with histological diagnosis of PSC undergoing 3 T MRI and hepatological evaluation, was retrospectively enrolled. All MR examinations included diffusion-weighted imaging (DWI), T2-weighted (T2w) and T1-weighted (T1w) sequences, before and after administration of Gd-EOB-DTPA with the acquisition of both dynamic and hepato-biliary phase (HBP). Qualitative analysis was performed by assessment of liver parenchyma and biliary tract changes, also including biliary excretion of gadoxetic acid on HBP. Quantitative evaluation was conducted on liver parenchyma by measurement of apparent diffusion coefficient (ADC) and relative enhancement (RE) on 3-minute delayed phase and on HBP. Results of blood tests (ALT, ALP, GGT, total and direct bilirubin, albumin, and platelets) and transient elastography-derived liver stiffness measurements (TE-LSM) were collected and correlated with qualitative and quantitative MRI findings.

Among qualitative and quantitative findings, fibrosis visual assessment and RE had the best performance in estimating disease severity, showing a statistically significant correlation with both biomarkers of cholestasis and TE-LSM. Statistical analysis also revealed a significant correlation of gadoxetic acid biliary excretion with ALT and direct bilirubin, as well as of ADC with total bilirubin.

Qualitative and quantitative 3 T MR evaluation is a promising non-invasive method for the assessment of disease severity in patients with PSC.

Cholangiocarcinoma (CCA) represents a global health challenge, with rising incidence and mortality rates. This study aimed to elucidate the clinical course and practices of CCA in Latin America.

This observational cohort study investigated individuals diagnosed with CCA between 2010 and 2023 at five referral centres across Latin America. Demographic, biochemical, and clinical data were analysed.

A total of 309 patients were enrolled, demonstrating a balanced distribution of CCA subtypes (intrahepatic, perihilar, and distal), with Hispanics and Caucasians as the predominant ethnic groups, followed by Africans. Major risk factors identified included age, diabetes, obesity, MASLD, bile duct stones, and cholecystitis. Disparities in overweight/obesity prevalence were noted among CCA subtypes and ethnicities, with higher rates in extrahepatic CCA and among Hispanics and Caucasians. At diagnosis, 72% of patients had ECOG-PS scores of 0-1, with disease presentations ranging from localized (47%) to locally advanced (19%) and metastatic (34%). Patients who did not receive any anti-cancer therapy exhibited a median survival of 2.3 months. Survival rates significantly improved across treatment modalities, with surgery yielding the longest (34 months), followed by chemotherapy (8 months). Notably, Africans presented with worse ECOG-PS scores and more advanced disease, while Hispanics were less frequently treated with chemotherapy for advanced disease, contributing to lower survival rates (8.3 and 6 months, respectively) compared to Caucasians (12.6 months).

The high prevalence of late-stage CCA diagnosis in Latin America, particularly among individuals of African ethnicity, coupled with a significant proportion of Hispanic patients not receiving chemotherapy, underscores the dismal prognosis for these patients. These findings reveal structural challenges in cancer screening and healthcare access among diverse ethnic backgrounds and lower socioeconomic statuses in the region. Urgent measures are needed, including the identification of preventable risk factors, raising awareness among high-risk populations, and establishing equitable health coverage to address these disparities.

European Union's Horizon 2020 R&I Program, Incyte Bioscience International Sàrl, and European Association for the Study of the Liver (EASL).

Our aim was twofold. First, to validate Anali scores with and without gadolinium (ANALIGd and ANALINoGd) in primary sclerosing cholangitis (PSC) patients. Second, to compare the ANALIs prognostic ability with the recently-proposed potential functional stricture (PFS).

This retrospective study included 123 patients with a mean age of 41.5 years, who underwent gadoxetic acid-enahnced MRI (GA-MRI). Five readers independently evaluated all images for calculation of ANALIGd and ANALINoGd scores based upon following criteria: intrahepatic bile duct change severity, hepatic dysmorphia, liver parenchymal heterogeneity, and portal hypertension. In addition, hepatobiliary contrast excretion into first-order bile ducts was evaluated on 20-minute hepatobiliary-phase (HBP) images to assess PFS. Inter- and intrareader agreement were calculated (Fleiss´and Cohen kappas). Kaplan-Meier curves were generated for survival analysis. ANALINoGd, ANALIGd, and PFS were correlated with clinical scores, labs and outcomes (Cox regression analysis).

Inter-reader agreement was almost perfect (ϰ = 0.81) for PFS, but only moderate-(ϰ = 0.55) for binary ANALINoGd. For binary ANALIGd, the agreement was slightly better on HBP (ϰ = 0.64) than on arterial-phase (AP) (ϰ = 0.53). Univariate Cox regression showed that outcomes for decompensated cirrhosis, orthotopic liver transplantation or death significantly correlated with PFS (HR (hazard ratio) = 3.15, p < 0.001), ANALINoGd (HR = 6.42, p < 0.001), ANALIGdHBP (HR = 3.66, p < 0.001) and ANALIGdAP (HR = 3.79, p < 0.001). Multivariate analysis identified the PFS, all three ANALI scores, and Revised Mayo Risk Score as independent risk factors for outcomes (HR 3.12, p < 0.001; 6.12, p < 0.001; 3.56, p < 0.001;3.59, p < 0.001; and 4.13, p < 0.001, respectively).

ANALINoGd and GA-MRI-derived ANALI scores and PFS could noninvasively predict outcomes in PSC patients.

The combined use of Anali scores and the potential functional stricture (PFS), both derived from unenhanced-, and gadoxetic acid enhanced-MRI, could be applied as a diagnostic and prognostic imaging surrogate for counselling and monitoring primary sclerosing cholangitis patients.

Primary sclerosing cholangitis patients require radiological monitoring to assess disease stability and for the presence and type of complications. A contrast-enhanced MRI algorithm based on potential functional stricture and ANALI scores risk-stratified these patients. Unenhanced ANALI score had a high negative predictive value, indicating some primary sclerosing cholangitis patients can undergo non-contrast MRI surveillance.