Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy without treatment options beyond liver transplantation. The gut-liver axis, especially the role of gut microbes, has emerged as a crucial pathway contributing to PSC pathogenesis. Recent research has revealed Enterococcus (E.) faecalis and its virulence factor cytolysin to increase mortality risk in patients with alcohol-associated hepatitis. Thus, we studied the role of enterococci, particularly E. faecalis and its virulence factor genes cytolysin and gelatinase, in faecal samples from patients with PSC.

To assess the relevance of Enterococcus species, we performed 16S rRNA gene amplicon analysis in faecal samples from 60 patients with PSC. We validated our findings by qPCR of faecal microbial DNA in an extended cohort of 105 patients with PSC, 104 patients with inflammatory bowel disease (IBD) and 68 healthy subjects.

High-throughput 16S rRNA amplicon analysis revealed an increased relative abundance of enterococci in PSC patients compared with healthy controls and IBD patients, respectively, (p < 0.0001). PSC patients with high enterococci abundance had a decreased probability of transplant-free survival (p = 0.028). E. faecalis and its virulence factors cytolysin and gelatinase were more abundant in patients with PSC. Higher faecal cytolysin was associated with lower overall survival (p = 0.04), while survival was independent of gelatinase levels.

Our data highlight the association of E. faecalis and faecal cytolysin with lower survival in patients with PSC. These data should prompt further research into the pathogenic role of cytolysin-positive E. faecalis, and to explore its role as a potential therapeutic target.

Primary sclerosing cholangitis (PSC) is a rare pathology seen in patients with inflammatory bowel disease (IBD), especially ulcerative colitis. PSC increases patients' morbidity and requires the attention of a multidisciplinary team as those patients require frequent colonoscopies and biopsies due to the elevated risk of malignancy, biliary screening and management of progressive disease that could leave patients in liver failure requiring liver transplant. Some consider this a separate form of IBD in addition to Crohn's and ulcerative colitis. These patients should be monitored closely and managed carefully due to implications of ongoing management on quality of life and survival.

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.

Eosinophilic cholangitis (EC) is a rare condition characterized by eosinophilic infiltration of the bile ducts, often mimicking diseases like primary sclerosing cholangitis or cholangiocarcinoma. We report the case of a 32-year-old man with severe epigastric pain and elevated liver function tests. Initial imaging revealed common bile duct dilation and multiple strictures, initially suggestive of primary sclerosing cholangitis. Multiple endoscopic retrograde cholangiopancreatographies with brushings showed benign cytology but revealed polysomy on fluorescence in situ hybridization. A biopsy confirmed EC. High-dose corticosteroids led to significant clinical improvement. This case underscores the importance of considering EC in the differential diagnosis of biliary diseases, as timely diagnosis and treatment can lead to excellent outcomes.

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.

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.

Inflammatory bowel disease (IBD) occurs in up to 70%-80% of patients with primary sclerosing cholangitis (PSC). Oral vancomycin therapy (OVT) has been reported to be effective in the treatment of IBD associated with PSC (IBD-PSC).

To examine the effectiveness and safety of OVT in the treatment of IBD-PSC by performing a systematic review and pooled analysis of the literature.

We performed a systematic review and pooled analysis of studies reporting IBD clinical response to OVT in IBD-PSC.

A systematic search was conducted in Cochrane Library, Embase, Google Scholar, Medline, PubMed, Scopus, and Web of Science from database inception to June 3, 2024. We included adult and pediatric studies that reported on clinical response (defined as any improvement in IBD-related clinical symptoms) of IBD-PSC patients treated with OVT (including pre- and post-liver transplantation cohorts). Pooled analyses of OVT response and safety were performed.

A total of 21 (open-label, non-controlled) studies including 290 patients with IBD-PSC treated with OVT were included. The median duration of OVT to treat IBD-PSC was 32.5 weeks (interquartile range (IQR): 19-83 weeks). The total daily dose of OVT ranged from 250 to 1500 mg. Concomitant treatment included the following: mesalamine in 14.5% (n = 42), advanced therapies in 10.7% (n = 31), and immunosuppressive agents in 14.1% (n = 41). Clinical response was noted in 47.6% (138/290) and clinical remission in 43.5% (100/230). The biochemical remission rate post-OVT was 68.8% (55/80) and endoscopic remission was 39.4% (80/203). Three studies (n = 11) reported no episodes of acute cholangitis while on OVT. Five studies (n = 69) reported an incidence rate of 8.7% of vancomycin-resistant enterococci post-OVT to treat IBD-PSC.

OVT was associated with clinical response/remission in almost half of patients with IBD-PSC with a favorable side effect profile. Further prospective randomized trials are needed to confirm the dosing, efficacy, treatment duration, and long-term safety of OVT for the treatment of IBD-PSC.

The study protocol was registered with PROSPERO a priori (no. CRD42023438341).

Hepatic ductopenia is a pathologic diagnosis characterized by a decrease in the number of intrahepatic bile ducts as a consequence of various underlying etiologies. Some etiologies, such as primary sclerosing cholangitis, primary biliary cholangitis, and ischemic cholangitis, often have distinctive imaging findings. In contrast, other causes such as chronic rejection following liver transplantation, drug-induced biliary injury, infection, malignancy such as lymphoma, and graft-versus-host disease may only have ancillary or non-specific imaging findings. Thus, diagnosing ductopenia in conditions with nonspecific imaging findings requires a multidimensional approach, including clinical evaluation, serological testing, imaging, and liver histology to identify the underlying cause. These etiologies lead to impaired bile flow, resulting in cholestasis, liver dysfunction, and, ultimately, cirrhosis and liver failure if the underlying cause remains untreated or undetected. In the majority of instances, individuals diagnosed with ductopenia exhibit a positive response to treatment addressing the root cause or cessation of the causative agent. This article focuses on acquired causes of ductopenia, its clinical manifestation, histopathology, imaging diagnosis, and management.

Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities.

Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA.

Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn's disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001).

We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC.

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.

Sarcoidosis is a multisystem granulomatous syndrome that arises from a persistent immune response to a triggering antigen(s). There is no "gold standard" test or algorithm for the diagnosis of sarcoidosis, making the diagnosis one of exclusion. The presentation of the disease varies substantially between individuals, in both the number of organs involved, and the manifestations seen in individual organs. These qualities dictate that health care providers diagnosing sarcoidosis must consider a wide range of possible alternative diagnoses, from across a range of presentations and medical specialties (infectious, inflammatory, cardiac, neurologic). Current guideline-based diagnosis of sarcoidosis recommends fulfillment of three criteria: 1) compatible clinical presentation and/or imaging 2) demonstration of granulomatous inflammation by biopsy (when possible) and, 3) exclusion of alternative causes, but do not provide guidance on standardized strategies for exclusion of alternative diagnoses. In this review, we provide a summary of the most common differential diagnoses for sarcoidosis involvement of lung, eye, skin, central nervous system, heart, liver, and kidney. We then propose a framework for testing to exclude alternative diagnoses based on pretest probability of sarcoidosis, defined as high (typical findings with sarcoidosis involvement confirmed in another organ), moderate (typical findings in a single organ), or low (atypical/findings suggesting of an alternative diagnosis). This work highlights the need for informed and careful exclusion of alternative diagnoses in sarcoidosis.

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.

Background: Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic liver disease that may lead to biliary strictures and destruction. It is associated with p-ANCA positivity and inflammatory bowel disease, typically ulcerative colitis. The aim of this study is to investigate the trends of inpatient healthcare utilization and mortality from 2008 to 2017 in the United States. Methods: The Nationwide Inpatient Sample (NIS) was examined to identify adult patients diagnosed with PSC between 2008 and 2017. Data on patient demographics, resource utilization, mortality, and PSC-related complications were collected. STATA version 16.0 was employed to perform forward stepwise multivariate regression analysis, generating adjusted odds ratios for both primary and secondary outcomes. Primary outcomes included the inpatient mortality rate and healthcare resource utilization (length of stay, total charges, and trends over the study period). Secondary outcomes focused on trends in associated comorbidities and malignancies in patients with PSC. Results: The average total charge increased by 32.2% ± 2.12 from USD 61,873 ± 2567 in 2008 to USD 91,262 ± 2961 in 2017. Concurrently, the average length of stay declined from 8.07 ± 0.18 days in 2008 to 7.27 ± 0.13 days in 2017. The APR-DRG severity of illness and risk of death significantly increased (major or extreme) during the study period (2008 to 2017), with severity rising from 73.6% to 82.7% (coefficient: 0.21, 95% CI: 0.13-0.28) and risk of death from 45.3% to 60.9% (coefficient: 0.15, 95% CI: 0.08-0.23). The proportion of patients with HCC increased from 1.3% to 7.9% (coefficient: 2.13, 95% CI: 1.9-2.8). Conversely, the percentage of patients with cholangiocarcinoma (CCA) decreased from 5.1% to 2.8% (coefficient: -0.36, 95% CI: -0.25 to -0.46). Conclusions: There was rising mortality and healthcare resource utilization among patients with PSC from the years 2008 to 2017. These trends were paralleled by increasing rates of decompensated cirrhosis, HCC, and liver transplants. However, the incidence of CCA decreased during this time period. African American patients with PSC had worse inpatient mortality outcomes and healthcare utilization as compared to white patients. Further studies are warranted to investigate a possible causal link amongst these trends.

Primary sclerosing cholangitis is a chronic liver disease associated with significant morbidity, mortality, and healthcare utilization. We conducted a systematic review and meta-analysis of population-based studies of the incidence and prevalence of primary sclerosing cholangitis.

Medline and Embase were systematically searched to identify population-based studies of a defined geographic area and reported the incidence or prevalence of primary sclerosing cholangitis in the general population. Meta-analyses, using random-effects, were performed to calculate overall and country-specific incidence (per 100 000 persons/year) and prevalence rates (per 100 000 persons) with 95% confidence intervals.

The 14 studies on incidence and the 12 for prevalence originated from North America, Asia, Europe, and Oceania. Incidence and prevalence rates of primary sclerosing cholangitis were 0.87 (95% confidence interval, 0.59-1.29) and 13.53 (95% confidence interval, 10.20-17.94) per 100 000 persons, respectively.

Both the prevalence and incidence of primary sclerosing cholangitis is low in the general population. Future studies on the incidence and prevalence of primary sclerosing cholangitis in the general population should be directed at Asia, Africa, and Latin America to allow for a more robust assessment of the global epidemiology of primary sclerosing cholangitis.

Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are found in more than 50% of individuals with ulcerative colitis (UC). We aimed to determine the prevalence of anti-αvβ6 in patients with primary sclerosing cholangitis (PSC) and their association with liver disease severity.

Four cohorts of pre-liver transplant patients with PSC were recruited. Patients with inflammatory bowel disease (IBD) and healthy controls (HCs) served as comparators. Total IgG and anti-αvβ6 levels were measured using enzyme-linked immunosorbent assay. Olink inflammation panel was run on a subset of samples. Multivariable linear regression analysis was performed to assess the association between anti-αvβ6 and indices of liver disease severity.

A total of 137 patients with PSC (including 76 with PSC-UC, 33 with PSC-Crohn's disease (CD), and 28 with PSC alone) and 160 controls (including 91 with IBD and 69 HCs) were enrolled. Anti-αvβ6 levels were significantly higher in PSC-UC and PSC-CD compared with PSC alone (P < .0001 and P < .003) and HCs (P < .0001 and P < .0001). However, anti-αvβ6 levels in PSC alone were not increased compared with HCs. In patients with PSC-IBD, anti-αvβ6 levels correlated with markers of liver disease severity, including alkaline phosphatase level (r = 0.32; P = .004), the revised Mayo PSC risk score (r = 0.25; P = .02), and liver stiffness measurement (r = 0.43; P = .008) after adjusting for age, gender, race/ethnicity, and IBD subtype. Additionally, anti-αvβ6 levels were associated with markers of systemic inflammation and tissue remodeling.

Anti-αvβ6 autoantibodies identify a subset of patients with PSC with concomitant IBD.

Survival in patients with autoimmune liver disease overlap syndromes (AILDOS) compared to those with single autoimmune liver disease is unclear.

To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death.

Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap (AIH-PBC) or autoimmune hepatitis and primary sclerosing cholangitis overlap (AIH-PSC) and were identified from three tertiary centres for this cohort study. Liver-related death or transplantation (liver-related mortality) was determined using a population-based data linkage system. Prognostic scores for liver-related death were compared for accuracy [including liver outcome score (LOS), Hepascore, Mayo Score, model for end-stage liver disease (MELD) score and MELD incorporated with serum sodium (MELD-Na) score].

Twenty-two AILDOS patients were followed for a median of 3.1 years (range, 0.35-7.7). Fourteen were female, the median age was 46.7 years (range, 17.8 to 82.1) and median Hepascore was 1 (range, 0.07-1). At five years post enrolment, 57% of patients remained free from liver-related mortality (74% AIH-PBC, 27% AIH-PSC). There was no significant difference in survival between AIH-PBC and AIH-PSC. LOS was a significant predictor of liver-related mortality (P < 0.05) in patients with AIH-PBC (n = 14) but not AIH-PSC (n = 8). A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients (P = 0.012, log-rank test, 100% sensitivity, 77.8% specificity) (Harrell's C-statistic 0.867). The MELD score, MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group.

Survival in the rare, AILDOS is unclear. The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients. Further trials investigating predictors of survival in AILDOS are required.

Primary sclerosing cholangitis (PSC) increases the risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients; however, there is a paucity of literature to suggest PSC alone as an independent risk factor for CRC. We aimed to determine if PSC is an independent risk factor for CRC in a large tertiary care medical center. Optimizing screening intervals is of great importance, given the burden and risks associated with a lifetime of colonoscopy screening.

This retrospective cohort study consists of patients diagnosed with PSC preceding IBD (PSC-IBD) and PSC-only before January 6, 2023 from a large, tertiary, academic medical center. Patients diagnosed with IBD concurrently or before PSC were excluded to reduce IBD's impact on CRC risk. Demographic data and colonoscopy findings were collected and assessed.

Overall, 140 patients from all NYU Langone Health clinical settings were included. Patients with PSC-IBD were more likely to be diagnosed with CRC (23.3% vs. 1.8%, p < 0.01) and either low-grade or uncharacterized dysplasia (16.7% vs. 0.0%, p < 0.01) compared with those with PSC-only. Among PSC-only patients, the estimated CRC risk was significantly elevated compared with that expected of the standard NYU Langone population (SIR 9.2, 95% CI 1.1, 33.2).

Our study revealed a significantly heightened CRC risk in PSC-IBD patients compared with those with PSC-only. Importantly, individuals with PSC-only also face a greater CRC risk compared with the general population. Individuals with PSC-alone may require extended screening and surveillance colonoscopy intervals compared with those with PSC-IBD, yet still require more frequent monitoring than screening guidelines recommend for the general population.

Background: Gallbladder cancer (GBC) is a rare entity with a poor prognosis, usually discovered late due to nonspecific symptoms; therefore, over the last years, attention has been focused on identifying the risk factors for developing this malignancy in order to provide an early diagnosis, as well as new prognostic factors in order to modulate the long-term evolution of such cases. The aim of this review is to discuss both major risk factors and prognostic factors in GBC for a better understanding and integration of relevant and currently available information. Methods: A literature search was performed using Cochrane Library, PubMed, Google Scholar, Elsevier, and Web of Science; studies published after the year of 2000, in English, were reviewed. Results: Over time, risk factors associated with the development of GBC have been identified, which outline the profile of patients with this disease. The most important prognostic factors in GBC remain TNM staging, safety margin, and R0 status, along with perineural invasion and lymphovascular invasion. Both the technique and experience of the surgeons and a pathological examination that ensures final staging are particularly important and increase the chances of survival of the patients. Conclusions: improvements in surgical techniques and pathological analyses might provide better and more consistent guidance for medical staff in the management of patients with GBC.

The Farnesoid X receptor (FXR) is a key transcription factor that is involved in the bile acid signaling network. The modulation of the FXR activity influences glucose and lipid homeostasis, reduces obesity and insulin resistance, as well as it regulates the pathogenesis of inflammatory and metabolic disorders. FXR ligands have therefore emerged in drug discovery as promising therapeutic agents for the prevention and treatment of gastrointestinal and liver diseases, including cancer.

Recent advances in the field of FXR modulators are reviewed, with a particular attention on patent applications filed in the past 5 years related to both the discovery and development of FXR targeting drugs.

FXR agonists have proven their efficacy and safety in humans and have shown a significant potential as clinical agents to treat metabolic and inflammatory associated conditions. However, several challenges, including adverse events such as pruritus, remain to be solved. Current studies aim to gain insights into the pathophysiological mechanisms by which FXR regulates metabolism and inflammation in terms of tissue/organ/isoform-specificity, post-translational modifications and coregulatory proteins, on the route of novel, improved FXR modulators.

The American Society for Gastrointestinal Endoscopy recommends prophylactic antibiotics before endoscopic retrograde cholangiopancreatography (ERCP) in primary sclerosing cholangitis (PSC). We assessed the impact of this approach on the incidence of post-ERCP outcomes using nationwide data.

Using 2015-2021 Nationwide Inpatient Sample data and relevant ICD-10 codes, we analyzed adult hospitalizations for PSC who underwent ERCP, with and without antibiotic prophylaxis. Hierarchical multivariate logistic regression analysis was used to assess the association between prophylactic antibiotic use and post-ERCP complications including sepsis, acute cholangitis, and acute pancreatitis.

We analyzed 32,972 hospitalizations for PSC involving ERCP, with 12,891 admissions (39.1%) receiving antibiotics before ERCP (cases) and 20,081 (60.9%) serving as controls. Cases were older than controls (mean age: 64.2 ± 8.6 vs. 61.3 ± 6.1 years; P = 0.020). Compared with controls, hospitalizations with antibiotic prophylaxis had a higher male population (7,541 (58.5%) vs. 11,265 (56.1%); P < 0.001) and higher comorbidity burden (Charlson comorbidity index score of ≥2: 5,867 (45.5%) of cases vs. 8,996 (44.8%) of controls; P = 0.01). Incidence of post-ERCP septicemia was 19.1% (6,275) with 2,935 incidences (22.8%) among cases compared with 3,340 (16.6%) among controls. Antibiotic prophylaxis did not significantly improve the odds of septicemia (aOR: 0.85; 95% CI: 0.77 - 1.09; P = 0.179). Approximately 2,271 (6.9%) cases of acute cholangitis and 5,625 (17.1%) cases of acute post-ERCP pancreatitis were recorded. After adjustments for multiple variables, no significant difference was observed in the odds of cholangitis (aOR: 0.87; 95% CI: 0.98 - 1.45; P = 0.08). However, antibiotic prophylaxis was correlated with a statistically significant reduction in the odds ratio of acute post-ERCP pancreatitis (aOR: 0.61; 95% CI: 0.57 - 0.66; P < 0.001).

The use of antibiotic prophylaxis in hospitalizations with PSC was correlated with a significant reduction in the odds of post-ERCP pancreatitis. Antibiotic prophylaxis did not improve the odds of post-ERCP sepsis or cholangitis. Prophylactic use of antibiotics should be individualized, considering both their anti-infective benefits and potential impact on the biochemical markers of liver disease.

Primary sclerosing cholangitis is an autoimmune illness affecting the intrahepatic and/or extrahepatic bile ducts that has a varying clinical history and no clear therapy. Recurrence of primary sclerosing cholangitis after transplantation can cause recurring liver failure, decreased survival, and the necessity for retransplant. Here, we explored the incidence of recurrence while also identifying the risk factors of primary sclerosing cholangitis.

In this retrospective cohort study, we collected demographic and clinical data from patients with a history of primary sclerosing cholangitis after liver transplant between 2011 and 2021. With SPSS software, we compared results in 2 groups of patients (with and without recurrent sclerosing biliary cholangitis) in terms of demographic and clinical variables.

The study included 408 patients. Lower donor age and the occurrence of acute cellularrejection were shown to be key risk factors for recurrence of primary sclerosing cholangitis. Acute cellularrejection showed the best likelihood of predicting primary sclerosing cholangitis recurrence. As the number of acute cellular rejection episodes increased, so did the chance of primary sclerosing cholangitis. Death rate of patients with recurrence of primary sclerosing cholangitis was 40.8% (n = 20 patients) compared with 18.9% (n = 68 patients) in those without recurrence (significant at P < .001).

The recurrence of primary sclerosing cholangitis had a detrimental effect on survival after liver transplant. Modifiable risk variables have the potentialto affecttherapies on care and prevention of primary sclerosing cholangitis recurrence. Donor age and acute cellular rejection were risk factors for decreased survival and higher primary sclerosing cholangitis recurrence. The use of mycophenolate (Cellcept) increased recurrence, but tacrolimus reduced mortality.

The relationship between primary sclerosing cholangitis (PSC) and biliary bile acids (BAs) remains unclear. Although a few studies have compared PSC biliary BAs with other diseases, they did not exclude the influence of cholestasis, which affects the composition of BAs. We compared biliary BAs and microbiota among patients with PSC, controls without cholestasis, and controls with cholestasis, based on the hypothesis that alterations in BAs underlie the pathophysiology of PSC.

Bile samples were obtained using endoscopic retrograde cholangiopancreatography from patients with PSC (n = 14), non-hepato-pancreato-biliary patients without cholestasis (n = 15), and patients with cholestasis (n = 13).

The BA profiles showed that patients with PSC and cholestasis controls had significantly lower secondary BAs than non-cholestasis controls, as expected, whereas the ratio of cholic acid/chenodeoxycholic acid in patients with PSC was significantly lower despite cholestasis, and the ratio of (cholic acid + deoxycholic acid)/(chenodeoxycholic acid + lithocholic acid) in patients with PSC was significantly lower than that in the controls with or without cholestasis. The BA ratio in the bile of patients with PSC showed a similar trend in the serum. Moreover, there were correlations between the alteration of BAs and clinical data that differed from those of the cholestasis controls. Biliary microbiota did not differ among the groups.

Patients with PSC showed characteristic biliary and serum BA compositions that were different from those in other groups. These findings suggest that the BA synthesis system in patients with PSC differs from that in controls and patients with other cholestatic diseases. Our approach to assessing BAs provides insights into the pathophysiology of PSC.

Imaging markers of biliary disease in primary sclerosing cholangitis (PSC) have potential for use in clinical and trial disease monitoring. Herein, we evaluate how quantitative magnetic resonance cholangiopancreatography (MRCP) metrics change over time, as per the natural history of disease.

Individuals with PSC were prospectively scanned using non-contrast MRCP. Quantitative metrics were calculated using MRCP+ post-processing software to assess duct diameters and dilated and strictured regions. Additionally, a hepatopancreatobiliary radiologist (blinded to clinical details, biochemistry and quantitative biliary metrics) reported each scan, including ductal disease assessment according to the modified Amsterdam Cholangiographic Score (MAS).

At baseline, 14 quantitative MRCP+ metrics were found to be significantly different in patients with PSC (N = 55) compared to those with primary biliary cholangitis (N = 55), autoimmune hepatitis (N = 57) and healthy controls (N = 18). In PSC specifically, baseline metrics quantifying the number of strictures and the number and length of bile ducts correlated with the MAS, transient elastography and serum ALP values (p < 0.01 for all correlations). Over a median 371-day follow-up (range: 364-462), 29 patients with PSC underwent repeat MRCP, of whom 15 exhibited quantitative changes in MRCP+ metrics. Compared to baseline, quantitative MRCP+ identified an increasing number of strictures over time (p < 0.05). Comparatively, no significant differences in biochemistry, elastography or the MAS were observed between timepoints. Quantitative MRCP+ metrics remained stable in non-PSC liver disease.

Quantitative MRCP+ identifies changes in ductal disease over time in PSC, despite stability in biochemistry, liver stiffness and radiologist-derived cholangiographic assessment (trial registration: ISRCTN39463479).

Crohn's disease and ulcerative colitis are forms of inflammatory bowel disease affecting approximately 1% of the population. Their typical features include chronic diarrhea, abdominal pain, and weight loss. Extraintestinal manifestations may coincide with or precede the diagnosis of these diseases. Primary sclerosing cholangitis is one such extraintestinal manifestation. Although many papers on this field have been published, bibliometric analysis still needs to be conducted. This article summarizes the current research progress through a bibliometric study, provides an overview of the research status in this field, and analyzes recent research trends.

Publications on inflammatory bowel disease and primary sclerosing cholangitis from January 1, 2008, to August 31, 2023, were extracted from the Web of Science Core Collection. VOSviewer and CiteSpace were used to perform a bibliometric and visual study.

There are 1499 relevant articles, and the number of articles in this field has been relatively stable in recent years. The results indicate that Karlson TH from the University of Oslo has the highest cumulative number of publications. The institution with the highest publication output is the Mayo Clinic, and the United States leads in article production, occupying a dominant position. Keyword analysis reveals 4079 keywords, with primary sclerosing cholangitis, inflammatory bowel disease, and ulcerative colitis being the most frequently occurring keywords.

Research on the association between inflammatory bowel disease and primary sclerosing cholangitis is steadily advancing, with the United States leading in publication output globally. China needs to invest more in research in this area, and collaboration among institutions should be strengthened. The research hotspots revolve around the association between inflammatory bowel disease and primary sclerosing cholangitis, gut microbiota, and other fields.

The gut microbiome is acknowledged as a key determinant of human health, and technological progress in the past two decades has enabled the deciphering of its composition and functions and its role in human disorders. Therefore, manipulation of the gut microbiome has emerged as a promising therapeutic option for communicable and non-communicable disorders. Full exploitation of current therapeutic microbiome modulators (including probiotics, prebiotics, and faecal microbiota transplantation) is hindered by several factors, including poor precision, regulatory and safety issues, and the impossibility of providing reproducible and targeted treatments. Artificial microbiota therapeutics (which include a wide range of products, such as microbiota consortia, bacteriophages, bacterial metabolites, and engineered probiotics) have appeared as an evolution of current microbiota modulators, as they promise safe and reproducible effects, with variable levels of precision via different pathways. We describe the landscape of artificial microbiome therapeutics, from those already on the market to those still in the pipeline, and outline the major challenges for positioning these therapeutics in clinical practice.

Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are all immune-mediated chronic inflammatory liver diseases. Autoimmune liver diseases are rare, making identification and treatment difficult. To improve clinical outcomes and enhance patient quality of life, we performed an epidemiological study of autoimmune liver diseases based on real-world comprehensive data.

We used National Health Insurance Service claims data in Korea from 2005 to 2019. Patients were identified using the International Classification of Disease 10th Revision code, and rare intractable disease codes assigned according to the strict diagnostic criteria. In the AIH cohort, 8,572 (83.9%) were females and the mean age at diagnosis was 56.3 ± 14.3 years. PBC also showed female dominance (83.3%) and the mean age was 57.8 ± 12.6 years. Patients with PSC showed no sex predominance and had a mean age of 57.8 ± 21.5 years. During the study period, there were 10,212, 6,784, and 888 AIH, PBC, and PSC patients, respectively. The prevalence of AIH, PBC, and PSC in 2019 were 18.4, 11.8, and 1.5 per 100,000 population, while the corresponding incidences were 2.3, 1.4, and 0.3 per 100,000 population, respectively. Analysis of sex-age-standardized data showed that the annual prevalence of these diseases is increasing. The 10-year survival rates were 89.8%, 74.9%, and 73.4% for AIH, PBC, and PSC, respectively.

The number of patients with autoimmune liver disease in South Korea is increasing over time. Further research on autoimmune liver disease is needed to fulfill unmet clinical needs.

There are two sub-phenotypes of large-duct primary sclerosing cholangitis (PSC): isolated intrahepatic PSC (IIPSC) and extrahepatic disease with or without intrahepatic (extra/intrahepatic).

This study examined the differences in outcomes in patients with IIPSC compared to extra/intrahepatic and small-duct PSC.

Patients with PSC treated at our institution from 1998 to 2019 were investigated. Biochemistries, clinical events, and survival were assessed by chart review and National Death Index. Cox-proportional hazards were used to determine the risk of clinical outcomes based on biliary tract involvement.

Our cohort comprised 442 patients with large-duct PSC (57 had IIPSC, 385 had extra/intrahepatic PSC) and 23 with small-duct PSC. Median follow-up in the IIPSC group was not significantly different from the extra/intrahepatic group [7 vs. 6 years, P = 0.06]. Except for lower age (mean 37.9 vs. 43.0 years, P = 0.045), the IIPSC group was not different from the extra/intrahepatic. The IIPSC group had longer transplant-free survival (log-rank P = 0.001) with a significantly lower risk for liver transplantation (12% vs. 34%, P < 0.001). The IIPSC group had a lower risk of death or transplantation than the extra/intrahepatic PSC group [HR: 0.34, 95% CI: 0.17-0.67, P < 0.001]. No bile duct or gallbladder cancers developed in patients with IIPSC, compared to 24 in the extra/intrahepatic group. The clinical characteristics and outcomes of IIPSC were similar to 23 individuals with small-duct PSC.

Patients with IIPSC have a favorable prognosis similar to small-duct PSC. These data are important for counseling patients and designing therapeutic trials for PSC.

Biliary-pattern injury in the liver (eg, duct injury, ductular reaction, cholestasis) can occur in several conditions, including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), large duct obstruction (LDO), and drug-induced liver injury (DILI). While the histologic changes in these conditions have been individually well described, distinguishing among them remains often challenging, particularly when biopsy samples are limited in size, robust clinical information is unavailable, and/or the pathologist does not feel confident in evaluating liver disease. This study evaluated histologic features that could aid the diagnosis of biliary-pattern injury on biopsy. We reviewed 121 liver biopsies from clinically confirmed cases of PBC, PSC, chronic LDO, or DILI for multiple clinical and histologic parameters. The rates of these histologic findings were then compared among different entities. Onion-skin fibrosis was seen in 14% of PSC in comparison to 0%, 5%, and 0% of PBC, DILI, and chronic LDO (P = 0.031). Florid duct lesions were identified in 21% of PBC compared to 2% of PSC and 0% of DILI and LDO (P = 0.0065). Similarly, 42% of PBC showed lobular granulomas, compared to 7% of PSC, 11% of DILI, and 33% of chronic LDO (P = 0.0001). Cholestasis was more commonly seen in DILI (42%) and chronic LDO (83%) than in PBC (4%) and PSC (16%) (P < 0.0001). Lobular chronic inflammation was found in a significantly higher percentage of PBC and LDO than of PSC and DILI (P = 0.0009). There were significantly fewer cases of PBC showing neutrophils in ductular reaction than PSC, DILI, and LDO (P = 0.0063). Histologic findings that can help suggest a diagnosis in liver biopsies with biliary-pattern injury include florid duct lesions, lobular granulomas, lack of neutrophils in ductular reaction, and lobular chronic inflammation in PBC; onion-skin fibrosis in PSC; cholestasis and feathery degeneration in DILI; and lobular granulomas, lobular chronic inflammation, cholestasis, and feathery degeneration in chronic LDO. These findings are likely most helpful when complicating factors interfere with biopsy interpretation.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease associated with inflammation, fibrosis, and destruction of intra- and extrahepatic bile ducts. Despite substantial recent advances in our understanding of PSC, the only proven treatment of PSC is liver transplantation. There is an urgent unmet need to find medical therapies for this disorder.

Multiple drugs are currently under evaluation as therapeutic options for this disease. This article summarizes the literature on the various novel therapeutic options that have been investigated and are currently under development for the treatment of PSC.

In the next decade, more than one drug will likely be approved for the treatment of the disease, and we will be looking at combination therapies for the optimal management of the disease.

With the growing recognition of IgG4-related hepatobiliary disease, establishing a definitive diagnosis relies mainly on a combination of clinical findings, serological markers, and imaging modalities. However, the role of histopathological evaluation remains indispensable, particularly in cases necessitating differential diagnosis or malignancy exclusion. While diagnosing IgG4-related hepatobiliary disease through surgical resection specimens is often straightforward, pathologists encounter substantial challenges when evaluating biopsies. The increasing rarity of surgical interventions exacerbates this due to improved disease recognition and suspicion. Numerous confounding factors, including the absence of the characteristic histologic features, limited tissue sample size, biopsy artifacts, and the limited value of IgG4 counts, further complicate the diagnostic process. Additionally, many other disorders exhibit clinical and histological features that overlap with IgG4-related disease, intensifying the complexity of interpreting biopsy specimens. This article explores the clinical and histomorphologic features of IgG4-related hepatobiliary disease and its potential mimickers. It offers valuable insights for pathologists and clinicians when confronted with biopsy specimens from hepatobiliary organs.

Primary sclerosing cholangitis (PSC) is considered an immunologically mediated disease. However, some of its features are not consistent with the typical profile of autoimmune conditions. PSC is characterized by progressive biliary fibrosis that may ultimately result in the eventual development of cirrhosis. In recent years, multiple studies have reported that the incidence and prevalence of this disease are on the rise. Consequently, patients are often diagnosed without symptoms or signs of advanced liver disease, although many still present with signs of decompensated liver disease. This article discusses the epidemiology, clinical presentation, and diagnostic workup in patients with PSC.

Cholangiocarcinoma (CCA) is a deadly complication observed in the setting of primary sclerosing cholangitis (PSC). When symptoms develop and CCA is diagnosed, it is usually at an advanced stage. Median survival is less than 12 months. Early identification of CCA leads to improved outcomes. Although diagnostic tests have excellent specificity, they are plagued by low sensitivity. No surveillance strategies have been widely agreed upon, but most societies recommend measurement of serum carbohydrate antigen 19-9 and MRCP every 6 to 12 months in patients with PSC. Advances in understanding of the genetic factors that lead to CCA are awaited.

Primary sclerosing cholangitis is a progressive cholestatic liver disease that causes stricturing of the intra and extrahepatic bile ducts that can lead to cirrhosis and end stage liver disease. Effective medical therapy has been elusive, but a course of ursodeoxycholic acid may be prescribed at doses of 17-23 mg/kg/day for up to a year to determine if a reduction in serum alkaline phosphatase is observed. A number of drugs are under investigation, including FXR agonists with choleretic and antimicrobial properties. Liver transplantation for PSC has one of the highest survival rates, but recurrent PSC is seen in up to 25% of recipients.

Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory liver disease characterized by biliary strictures and cholestasis. Due to the lack of effective serological indicators for diagnosis and prognosis, in the present study, we examined the potentiality of the saliva proteome to comprehensively screen for novel biomarkers.

Saliva samples of PSC patients and healthy controls were processed and subsequently analyzed using a liquid chromatography-tandem mass spectrometry technique. A bioinformatic approach was applied to detect the differentially expressed proteins, their related biological functions and pathways, and the correlation with the clinical evidence in order to identify a possible marker for the PSC group.

We identified 25 differentially expressed proteins in PSC patients when compared to the healthy control group. Among them, eight proteins exhibited area under the curve values up to 0.800, suggesting these saliva proteins as good discriminators between the two groups. Multiple positive correlations were also identified between the dysregulated salivary proteins and increased serum alkaline phosphatase levels and the presence of ulcerative colitis. Pathway analysis revealed significant enrichments in the immune system, neutrophil degranulation, and in the interleukine-17 signaling pathway.

We demonstrated the potentiality of saliva as a useful biofluid to obtain a fingerprint of the pathology, suggesting disulfide-isomerase A3 and peroxiredoxin-5 as the better discriminating proteins in PSC patients. Hence, analysis of saliva proteins could become, in future, a useful tool in the screening of patients with suspected PSC.