CONCLUSIONS: Although the overlap between both pathologies is rare, it is important to diagnose it, since treatment may be different, and screening for different complications may be required.
Recurrent primary sclerosing cholangitis (rPSC) remains a significant challenge. Although Klebsiella pneumoniae (Kp) has been implicated in PSC pathogenesis, its association with rPSC remains unclear. We retrospectively analyzed 62 patients who underwent LT for PSC at our institution between 1996 and July 2024 and survived for more than 1 year. We assessed the association between Kp detection in postoperative clinical cultures and rPSC. rPSC was observed in 22 of 62 patients (35.5%). Kp was...
CONCLUSION: This meta-analysis provides an updated synthesis of PSC epidemiology, extending prior work by incorporating detailed subgroup analyses across IBD phenotype, PSC subtype, geographic region, socioeconomic context, diagnostic modality, case-ascertainment method, and time period, which are dimensions not comprehensively addressed in previous meta-analyses. PSC remains a rare disease in the general population but is substantially more prevalent among individuals with IBD. Marked...
CONCLUSIONS: Sarcopenia in PSC-colitis may reflect proportionate growth impairment, "short but not skinny," rather than catabolic wasting. This phenotype, characterized by persistent height deficits despite weight recovery and mild colitis, may suggest hepatobiliary or other mechanisms distinct from the gut inflammation-driven sarcopenia in non-PSC colitis and the cachexia of end-stage liver disease.
Primary sclerosing cholangitis (PSC) is a chronic, progressing cholestatic disease that often co-occurs with inflammatory bowel disease (PSC-IBD). PSC-IBD affecting the colon (PSC-ulcerative colitis or PSC-UC) resembles clinical UC, but is characterised by less severe disease flares, right-colon predominance, and a greater lifetime risk of colorectal cancer than UC alone. To elucidate differences in the underlying biology between PSC-UC and UC, here we combine single-cell mRNA and antigen...
Mesenchymal stem cells (MSCs) have emerged as promising therapeutic candidates for a wide range of intrahepatic and extrahepatic biliary diseases. However, their clinical application remains limited by an incomplete understanding of underlying mechanisms and heterogeneous therapeutic outcomes. This review provides a comprehensive overview of recent advances in MSC-based therapies for biliary system diseases, including primary biliary cholangitis, intrahepatic biliary fibrosis and cirrhosis,...
CONCLUSIONS: This review highlights a patient-partnered research team's experiential insights to bridge the gap between published guidance and real-world practice, reinforcing how authentic patient-researcher partnerships can drive more inclusive and impactful basic and translational science.
CONCLUSIONS: While few patients with PSC develop GBN, this subgroup is more likely to develop CCA. Consequently, once GBN is detected, clinicians should consider more intensive screening for CCA.
Autoimmune liver diseases (primary biliary cholangitis, PBC; primary sclerosing cholangitis, PSC; autoimmune hepatitis, AIH) are three distinct, organ-specific autoimmune disorders that share loss of tolerance as the central pathophysiological mechanism but differ in target tissue, age of onset, genetic background, and environmental susceptibility. This review examines how environmental exposures modulate tolerance failure and tissue-directed injury across the three phenotypes. The signal is...
CONCLUSIONS: IBD is associated with increased MPN risk, and IBD-MPNs coexistence is associated with worse IBD-related complications and malignancy risk.
Vanishing bile duct syndrome, VBDS, is a rare disease that is poorly understood and is a term used to loosely describe a group of disorders associated with the progressive destruction of intrahepatic ducts. This syndrome ultimately leads to cholestasis. There are many potential etiologies for this disease including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune diseases, medications, genetic abnormalities, infectious causes, or neoplastic disorders. The...
CONCLUSION: This case demonstrates the rapid and durable resolution of PSC-associated pruritus with JAK1 inhibition. Effective symptom control allowed deferral of LT driven primarily by quality-of-life impairment, with the patient remaining inactive on the waitlist. To our knowledge, this is the first reported case of successful treatment of PSC-associated pruritus with upadacitinib, supporting further investigation of JAK1 inhibition as a potential therapeutic strategy for cholestatic pruritus.
Overlap syndromes (OS) are mixed hepatitic-cholestatic variants of autoimmune liver diseases (AILD), characterized by features of autoimmune hepatitis (AIH), bile duct injury, and circulating autoantibodies related to primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). Few cases of PBC-PSC have also been reported. Following the recognition of immunoglobulin G4-related diseases (IgG4-RD), IgG4-hepatopathy, IgG4-AIH, and PSC-with high serum IgG4-related disorders are being...
CONCLUSIONS: Relative enhancement ratio of extrahepatic bile ducts at 20 min after gadoxetate disodium provides useful information in predicting adverse events in PSC patients and is complementary or superior to the currently used clinical scoring systems.
Background/Objectives: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease frequently requiring liver transplantation (LTx). The gut-liver axis, host genetics, and microbial dysbiosis are thought to contribute to disease progression and post-transplant outcomes. The FUT2 rs601338 polymorphism influences mucosal fucosylation, host-microbial interactions, and susceptibility to infection. This study aimed to investigate the association between FUT2 genotype, colonic mucosal...
Primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) exhibit a striking clinical comorbidity, with 60-80% of PSC patients concurrently harboring UC, yet the shared immunogenetic mechanisms remain poorly understood. Here, we constructed a multi-omics integrative framework to systematically dissect the cellular and molecular basis of this comorbidity. GWAS meta-analyses were performed for each disease, followed by tissue-level enrichment assessment using QTLEnrich, MAGMA, and gsMap...
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases characterized by bile duct injury that may progress to fibrosis, cirrhosis, liver failure, and malignancy and ultimately require liver transplantation. Although these diseases share several clinical features, they differ substantially in pathogenesis, clinical course, and therapeutic approaches. Ursodeoxycholic acid remains the standard first-line therapy for PBC; patients with an...
CONCLUSION: Our findings suggest that chymase is strongly associated with PSC pathogenesis and that INVA8001 may represent a promising new therapeutic candidate for hepatobiliary disorders, including PSC. Chymase inhibition simultaneously targets MC activation, inflammation, fibrosis, and biliary senescence, and offers a multifaceted approach to treating PSC and other MC-related disorders.
CONCLUSIONS: Quercetin likely exerts its therapeutic effects by targeting ANXA2 and modulating cholangiocyte pathogenicity. These findings highlight ANXA2 as a promising therapeutic target for treating advanced CCA and halting PSC-driven carcinogenesis.
CONCLUSION: This study delineates a preliminary metabolic-immune interactome in PSC from a genetic standpoint, offering novel insights into the disease's complex pathogenesis. The prioritized cohorts of metabolites and cytokines identified herein represent prime candidates for the future development of novel biomarkers and the design of targeted therapeutic interventions.
Ursodeoxycholic acid (UDCA) is a hydrophilic, non-toxic bile acid that represents the gold standard in the treatment of various cholestatic and hepatobiliary diseases. Its therapeutic benefit lies in its complex pleiotropic mechanism of action, including cytoprotection of hepatocytes and cholangiocytes, stimulation of hepatobiliary secretion, antiapoptotic effects, and immunomodulatory properties. This article comprehensively summarizes the pharmacological characteristics of UDCA and its...
Overlap syndrome between autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) is a rare condition in children and represents a diagnostic challenge due to the lack of standardized diagnostic criteria and the frequent presence of atypical clinical manifestations. We report the case of a seven-year-old girl presenting with chronic jaundice, severe hepatocellular cytolysis, polyclonal hypergammaglobulinemia, and biliary abnormalities detected on MRI. Liver histology confirmed AIH....
CONCLUSIONS: Over half of post‑OVT colonoscopies showed pan‑colonic histological remission, particularly in proximally dominant UC. Treating for ≥4 months further improved outcomes, helping identify which patients may benefit from OVT.
CONCLUSIONS: PSC-IBD patients who subsequently develop colorectal dysplasia exhibit a significantly higher frequency of aberrant p53 overexpression in benign colon biopsies, particularly from the right/proximal colon, obtained prior to dysplasia detection compared with IBD patients who do not develop dysplasia. These findings suggest that aberrant p53 overexpression in benign colon biopsies may help identify PSC-IBD patients at increased risk for colorectal dysplasia.
Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts. Altered bile acid (BA) profile was shown to trigger immune responses in the liver, contributing to inflammation and liver fibrosis. Here, we analyzed BAs, their precursors (oxysterols), surrogate markers of cholesterol synthesis as well as of absorption, and studied their association with clinical/ immunological parameters in PSC. We analyzed...
Intrahepatic lithiasis (IHL), defined as the presence of calculi within the intrahepatic bile ducts proximal to the hepatic confluence, has traditionally been considered rare in Western populations. However, increasing evidence suggests that Low-Phospholipid-Associated-Cholelithiasis (LPAC) syndrome, which is a genetic cholangiopathy caused by ABCB4 variants affecting biliary phospholipid secretion, represents a frequently underrecognized cause of IHL.The imaging spectrum of IHL varies according...