原発性硬化性胆管炎

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholangiopathy characterized by inflammation and fibrosis of intrahepatic and/or extrahepatic bile ducts. Its pathogenesis remains incompletely understood, and liver transplantation is currently the only curative treatment available. The diagnosis remains challenging, and no disease-specific biomarkers have been established. Recently, anti-integrin αvβ6 antibodies have emerged as promising serological biomarkers with high specificity for PSC. Advances in imaging modalities, including magnetic resonance cholangiopancreatography and peroral cholangioscopy, have improved diagnostic accuracy for PSC. Although various therapeutic approaches have been investigated, no treatment has been shown to improve the long-term outcomes. Microbiota-targeted therapies represent a promising emerging strategy. The clinical course of PSC, particularly in its early stages, is poorly defined. We propose a definition of early stage PSC consisting of two subtypes: small-duct PSC without liver fibrosis and large-duct PSC without cholestatic enzyme elevation or biliary strictures. Early intervention at this stage may improve the prognosis, thus highlighting the need for further validation.

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases that have undergone notable therapeutic advances in recent years. Recent advances in PBC have expanded treatment options beyond ursodeoxycholic acid, enabling earlier risk stratification and use of second-line therapies, allowing practitioners to personalize treatment. Meanwhile, multiple investigational agents are under evaluation in clinical trials for PSC, yet there remain no approved treatments. This review summarizes advances in epidemiology, diagnosis, and treatment of the underlying disease along with the extrahepatic manifestations associated with PBC and PSC. PBC has entered a treat-to-target era, while PSC remains without approved disease-modifying therapy despite a rapidly expanding trial pipeline.

BACKGROUND AND AIMS: N-glycans modulate glycoprotein structure and function and are altered during chronic inflammation. We sought to define the extent of serum and IgG N-glycan disruption in patients with decompensated liver cirrhosis from alcohol-related liver disease (ALD), primary sclerosing cholangitis (PSC), and ALD-related hepatocellular carcinoma (HCC). Finally, we aimed to examine whether serum and IgG glycosylation is associated with changes in Model for End-stage Liver Disease-Sodium (MELD-Na) scores, a clinical marker used to prioritise liver transplantation. METHODS: Serum samples were obtained from patients with ALD (n = 17), PSC (n = 7), ALD-related HCC (n = 4), and healthy controls (n = 10). N-glycans were released, fluorescently labelled, and profiled by hydrophilic interaction ultra performance liquid chromatography (HILIC-UPLC). Chromatograms were integrated into 46 and 23 glycan peaks for serum and IgG respectively. These peaks and their associated glycosylation traits were statistically compared with healthy controls using age- and sex-adjusted linear regression models. RESULTS: In serum, decompensated cirrhosis shows statistically significant shifts toward less complex, agalactosylated and asialylated biantennary glycans, accompanied by significant losses of highly branched, galactosylated and sialylated structures. IgG mirrored this pattern, which is characteristic of a pro-inflammatory signature, with increased agalactosylation and bisected glycan levels, along with reduced levels of digalactosylated and sialylated species. N-glycan profiles showed significant associations with MELD-Na scores, indicating that inflammatory processes in decompensated liver cirrhosis continue to reshape serum glycoproteins. CONCLUSION: Decompensated liver cirrhosis shows profound remodelling of serum and IgG N-glycans. These data establish a reference framework for terminal glycomic disruption in liver disease and highlight the potential value of incorporating glycosylation analysis into broader assessments of liver disease progression.

Cholestasis is caused by genetic disorders in 25% of cases. Our study aimed to describe the clinical and genetic profile of cholestasis and to demonstrate the importance of next-generation sequencing (NGS) in the etiologic diagnosis of genetic cholestasis. We included patients referred for cholestasis over a 10-year period. Molecular studies using NGS consisted of a 292-gene panel and/or whole exome sequencing. Our cohort included 70 patients from 66 unrelated families. A genetic diagnosis was established in 70% of the families. The most common diagnoses were Type 2 progressive familial intrahepatic cholestasis (n = 12), neonatal sclerosing cholangitis (n = 4), low phospholipid-associated cholelithiasis syndrome (n = 4), and Alagille syndrome (n = 4). The ABCB11 gene was most frequently mutated (15/46), with two recurrent variants, c.1062T>A (p.Tyr354*) and c.1826_1827dup (p.Ile610Glnfs*45), found in six and four families, respectively. Our results showed a 62% diagnostic yield of molecular testing using NGS in cholestasis. An accurate diagnosis was key to providing appropriate genetic counseling, guiding screening of variant carriers, and prenatal diagnosis.

OBJECTIVE: Primary sclerosing cholangitis (PSC) increases malignancy risk in inflammatory bowel disease (IBD), but whether this risk differs between Crohn's disease (CD) and ulcerative colitis (UC) remains poorly defined. This study compared the risk of colorectal cancer (CRC), gallbladder cancer (GBC) and cholangiocarcinoma (CCA) in patients with CD with colonic involvement and concomitant PSC (CD+PSC) versus UC with concomitant PSC (UC+PSC). METHODS: This retrospective propensity score-matched cohort study used the TriNetX Network (2001-2024) to identify adults with PSC and either CD with colonic involvement (ICD-10-CM K50.1, K50.8) or UC (K51). Cohorts were matched 1:1 on age, sex, race, body mass index, smoking status, C-reactive protein and erythrocyte sedimentation rate. The primary analysis employed Kaplan-Meier survival estimation with Cox proportional hazards regression. RESULTS: After matching, 1,084 pairs were analyzed (mean follow-up 5.3 ± 2.6 years). CRC risk did not differ between groups (30/1084 = 2.8% in both; HR 1, 95% CI 0.765-2.112). CD+PSC was associated with significantly lower risk of both GBC (0.9% vs. 1.2%; HR 0.199, 95% CI 0.045-0.885) and CCA (2.8% vs. 5.9%; HR 0.625, 95% CI 0.406-0.961) versus UC+PSC. The CCA finding was consistent across both time-to-event and odds ratio analyses, while the GBC difference reached significance only in the time-to-event analysis. CONCLUSIONS: Among patients with PSC-IBD, CRC risk appears comparable regardless of IBD subtype, suggesting that PSC may be the predominant contributor to CRC risk in this population. However, CD+PSC carries significantly lower risk of both GBC and CCA than UC+PSC, which may reflect differences in biliary disease phenotype or surveillance intensity and warrants prospective validation.