Journal of Hepatology

Check our December issue! This month's cover features the article "Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease" by Marti-Aguado and Calleja et al. (https://bit.ly/4ijfw6l) Full issue here: https://bit.ly/36khmDF EASL | The Home of Hepatology

WHAT IS YOUR DIAGNOSIS ❓ A 15-year-old male patient experienced two episodes of jaundice within one year, with a duration of several weeks. No fever, but mild diarrhea, poor appetite, and severe pruritus. Bilirubin (conjugated) was x 10 ULN, AST and ALT slightly incraesed, as well as AP. GGT was normal. Magnetic Resonance Cholangiopancreatography was normal. A liver biopsy was performed. 🤔What is your diagnosis? 1️⃣ Small-duct primary sclerosing cholangitis 2️⃣ Progressive familial intrahepatic cholestasis 3️⃣ Benign recurrent intrahepatic cholestasis 4️⃣ Dubin-Johnson/Rotor syndrome Full case here👉 https://bit.ly/48DaZXY EASL | The Home of Hepatology

Survodutide: Hope for Patients with MASH-Related Cirrhosis Survodutide, a dual agonist of glucagon and glucagon-like peptide-1 receptors, is being developed for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), which leads to cirrhosis in approximately 20% of cases. This multinational, non-randomized, open-label phase 1 clinical trial, demonstrated that survodutide is well tolerated in patients with cirrhosis, exhibiting pharmacokinetics similar to those of healthy controls and improving liver health markers. #OpenAccess here: https://bit.ly/4fzq7b7 EASL | The Home of Hepatology

Inflammasomes in chronic liver disease: Hepatic injury, fibrosis progression and systemic inflammation Chronic liver disease leads to hepatocellular injury that triggers a pro-inflammatory state in several parenchymal and non-parenchymal hepatic cell types, ultimately resulting in liver fibrosis, cirrhosis, portal hypertension and liver failure. Thus, an improved understanding of inflammasomes – as key molecular drivers of liver injury – may result in the development of novel diagnostic or prognostic biomarkers and effective therapeutics. In liver disease, innate immune cells respond to hepatic insults by activating cell-intrinsic inflammasomes via toll-like receptors and NF-κB, and by releasing pro-inflammatory cytokines (such as IL-1β, IL-18, TNF-α and IL-6). Subsequently, cells of the adaptive immune system are recruited to fuel hepatic inflammation and hepatic parenchymal cells may undergo gasdermin D-mediated programmed cell death, termed pyroptosis. With liver disease progression, there is a shift towards a type 2 inflammatory response, which promotes tissue repair but also fibrogenesis. Inflammasome activation may also occur at extrahepatic sites, such as the white adipose tissue in MASH (metabolic dysfunction-associated steatohepatitis). In end-stage liver disease, flares of inflammation (e.g., in severe alcohol-related hepatitis) that spark on a dysfunctional immune system, contribute to inflammasome-mediated liver injury and potentially result in organ dysfunction/failure, as seen in ACLF (acute-on-chronic liver failure). This review provides an overview of current concepts regarding inflammasome activation in liver disease progression, with a focus on related biomarkers and therapeutic approaches that are being developed for patients with liver disease. Review by Vlad Țâru, Gyongyi Szabo MD, PhD, Wajahat Mehal and Thomas Reiberger #OpenAccess here: https://lnkd.in/dgWjbKwH EASL | The Home of Hepatology

NTCP Polymorphisms and Their Impact on Hepatitis Delta Treatment Genetic polymorphisms of the sodium taurocholate cotransporting peptide (NTCP), which facilitate HBV/HDV entry into liver cells, have been identified. This study, demonstrates that NTCP rs17556915 polymorphisms influence baseline HDV RNA levels and treatment response to Bulevirtide in patients with chronic hepatitis Delta, with TT/CC carriers exhibiting a higher rate of virological nonresponse. Full text here: https://bit.ly/4hFLf1c EASL | The Home of Hepatology

✴ Hepatology Snapshot ✴ Intrahepatic immunity to hepatitis B virus By Valentina Venzin, Cristian G Beccaria, Francesco A., Valeria Fumagalli and Matteo Iannacone Find it here: https://lnkd.in/du9jvik6 EASL | The Home of Hepatology

WHAT IS YOUR DIAGNOSIS ❓ A 71-year-old male found to have elevated liver enzymes during post-operative Whipple resection for small bowel adenocarcinoma Liver tests: ALT 92 U/L AST 244 U/L Alkaline phosphatase 1444 U/L Work up for other causes of liver disease: Negative Imaging studies did not reveal abnormalities in the extrahepatic or intrahepatic biliary tree. A liver biopsy was performed. 🤔What is your diagnosis? 1️⃣ Sarcoidosis 2️⃣ Histiocyte-rich lymphoproliferative disorder 3️⃣ Mycobacterial granulomatous hepatitis 4️⃣ Drug-induced liver injury Full case here👉 https://bit.ly/48EmcaN EASL | The Home of Hepatology

Soluble Immune Mediators as novel Biomarkers for Early Rejection Risk in Pediatric Liver Transplantation Pediatric liver transplantation (pLT) necessitates lifelong immunosuppression due to the absence of reliable rejection biomarkers. This multicenter study, identified six soluble immune mediator signatures associated with one-year rejection-free survival. These findings may provide valuable insights for early rejection risk assessment and guide immunosuppression strategies in pediatric patients. #OpenAccess here: https://lnkd.in/d9cHGX5b EASL | The Home of Hepatology

Liver biopsy evaluation in MASH drug development: Think thrice, act wise During recent decades, the metabolic dysfunction-associated steatohepatitis (MASH) field has witnessed several paradigm shifts, including the recognition of liver fibrosis as the main predictor of major adverse liver outcomes. Throughout this evolution, liver histology has been recognised as one of the main hurdles in MASH drug development due to its invasive nature, associated cost, and high inter- and intra-reader variability. Collective experience demonstrates the importance of consistency in the central reading process, where consensus methods have emerged as appropriate ways to mitigate against well-known challenges. Using crystalized knowledge in the field, stakeholders should collectively work towards the next paradigm shift, where non-invasive biomarkers will be considered surrogate endpoints for accelerated approval. In this review, we provide an overview of the evolution of the regulatory histology endpoints and the liver biopsy reading process, within the MASH trial landscape, over recent decades; we then review the biggest challenges associated with liver biopsy endpoints. Finally, we discuss and provide recommendations on the best practices for liver biopsy evaluation in MASH drug development. Full text here: https://lnkd.in/dMnt832v Julie Dubourg EASL | The Home of Hepatology

GCDH: A Crucial Metabolic Switch to Stop Liver Cancer Growth and Enhance Immunotherapy Glutaryl-CoA dehydrogenase (GCDH) promotes protein crotonylation by converting glutaryl-CoA to crotonyl-CoA, which suppresses hepatocellular carcinoma (HCC) growth. This study published shows that GCDH enhances crotonylation, inhibiting key metabolic pathways like PPP and glycolysis, limiting the Warburg effect. GCDH overexpression suppresses HCC growth, induces cell senescence, and boosts anti-PD-1 therapy sensitivity. Full text here: https://lnkd.in/djnGFGXq EASL | The Home of Hepatology