Veille scientifique | Cholangite biliaire primitive (CBP), Cholangite sclérosante primitive (CSP), Hépatite auto-immune (HAI), Syndrome LPAC

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune-mediated destruction of intrahepatic bile ducts, leading to fibrosis, cirrhosis, and liver failure. Ursodeoxycholic acid remains the first-line treatment, but up to 40% of patients respond inadequately and continue to experience fatigue and pruritus. This therapeutic gap has recently been addressed by the approval of two new drugs, elafibranor and seladelpar, which activate peroxisome...

Xanthine oxidase (XO) and aldehyde oxidase (AO) are molybdenum-dependent flavoenzymes involved in purine catabolism and hepatic xenobiotic metabolism. This study aimed to assess XO and AO activities and molybdenum (Mo) content in liver tissue from liver graft donors and recipients with end-stage liver failure (ESLF). Liver tissue samples were obtained from 10 liver donors (LD; control group) and 30 patients with ESLF undergoing liver transplantation. The ESLF cohort was further divided by...

Primary sclerosing cholangitis (PSC) is a chronic inflammatory precursor associated with an increased risk of intrahepatic cholangiocarcinoma (ICC), yet identifying malignant features within the persistent inflammatory background remains challenging. In this study, a background-deviation framework was applied to explore malignant-associated determinants during PSC-associated cholangiocarcinogenesis. Single-cell RNA sequencing data from PSC, ICC tumor tissues, and adjacent non-tumor tissues were...

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Estimation of histological cirrhosis on diagnosis is useful for predicting prognosis in patients with primary biliary cholangitis (PBC). The pretreatment GLOBE score is associated with survival, but its relationship with histological cirrhosis remains unknown. We retrospectively investigated the pretreatment GLOBE score in PBC patients who had undergone liver biopsy. We analyzed the association between pretreatment GLOBE score and clinical findings, including histological cirrhosis and liver...

Eosinophilic cholangitis (EC) is a rare inflammatory biliary disorder that can mimic primary sclerosing cholangitis and cholangiocarcinoma. We performed a PRISMA 2020-guided systematic review to summarize diagnostic features, management, and outcomes. Web of Science, PubMed, MEDLINE, Embase, Scopus, and CINAHL were searched; 55 studies (55 patients) were included. Among cases with a preoperative impression (n=39), malignancy was suspected in 19 (48.7%). Among cases with reported localization...

CONCLUSIONS: Clinical judgement and Paris II classification differ in 20% of patients. Higher baseline ALP levels and kinetics may lead to misclassification. This may result in withholding of second line treatments in these patients.

CONCLUSIONS: A circulatory CXCL8^(+)CD14^(+) monocyte subset and intrahepatic IL-8^(+) macrophages were identified as potential contributors to PSC pathogenesis. HIS mouse models could mark a significant advance in translational research on human immune responses. Targeting the IL-8:CXCR1/2 axis may represent a promising therapeutic strategy and urges further investigation.

Perihilar cholangiocarcinoma (pCCA) frequently presents as an indeterminate perihilar biliary stricture. The diagnosis is often delayed or uncertain because of the limited sensitivity of conventional endobiliary sampling and blood-based markers, especially in patients with additional confounding conditions such as primary sclerosing cholangitis (PSC). This diagnostic ambiguity can significantly impact clinical outcomes as timely detection and accurate classification are critical for referral and...

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CONCLUSION: The GPS and its variants reliably predict recompensation in decompensated PBC, with the GPS showing superior accuracy. These tools can stratify risk and inform early intervention strategies.

Objective Anti-mitochondrial antibodies (AMA) are primarily used as serological markers for primary biliary cholangitis, but they have also been implicated in cardiac dysfunction and arrhythmias. This study aimed to investigate the association between AMA positivity, the right atrial low-voltage area (RA-LVA), and sick sinus syndrome (SSS) in patients with isolated cardiac involvement. Methods We retrospectively analyzed patients who underwent AMA testing at the Ogaki Municipal Hospital between...

A 70-year-old female patient was diagnosed with autoimmune hepatitis (AIH) at the age of 58 years based on antinuclear antibodies (1:1280) and liver biopsy findings. She received prednisolone (PSL). Over time, elevated levels of liver enzymes and alkaline phosphatase were observed, and 12 years later, a repeat liver biopsy revealed no signs of AIH but showed characteristics of primary biliary cholangitis (PBC). After reducing the PSL dose and starting ursodeoxycholic acid and pemafibrate, the...

Nuclear receptors are central regulators of metabolism¹, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)²; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that...

CONCLUSION: This umbrella meta-analysis provides the most comprehensive synthesis to date, supporting UDCA-fibrate combination therapy for biochemical response in PBC. However, evidence on survival and transplant-free outcomes remains insufficient.

CONCLUSIONS: The overall projected efficacy of continued BZF in terms of the NNT to prevent solid clinical endpoints was strong, also in case people had a relatively favourable ALP level (1.0-1.5xULN) after one year of UDCA. These findings highlight the potential clinical benefit of off-label BZF in UDCA-treated people without ALP normalisation.

CONCLUSION: CB attenuates experimental PSC by modulating BA and lipid homeostasis via the gut-liver axis, mediated through a novel dual mechanism involving SIRT1-PGC-1α pathway activation and direct receptor agonism. These findings not only highlight CB as a promising multi-target agent for PSC treatment, but also provide novel insights into the therapeutic modulation of metabolism in the gut-liver axis.

CONCLUSIONS: MR analysis suggested that there might be no significant causal associations between SLE, RA, AS, PBC, PsA, or AOSD and ITP, whereas PM, PSC, and SS might potentially show causal associations with ITP.

The incidence of acute-onset autoimmune hepatitis (A-AIH) is increasing, yet diagnosis remains challenging, especially in patients with recent hepatotoxic drug exposure. The clinical presentations of A-AIH and drug-induced autoimmune-like hepatitis (DI-ALH) at onset are often indistinguishable, complicating timely diagnosis. We conducted a three-center retrospective study in China, screening patients with acute liver injury, hepatotoxic drug exposure, and autoimmune features. Patients were...

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