Differential prevalence and prognostic value of metabolic syndrome components among patients with MASLD.

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming increasingly prevalent in the general population. This study aimed at describing the cardiometabolic burden of the MASLD population and to identify patients at the highest risk of all-cause mortality and liver fibrosis.

Methods: We analysed individuals with MASLD enrolled in the National Health and Nutrition Survey (NHANES) III study (N = 3,628) and in the NHANES 2017-2020 study (n = 2,618).

Hepatic real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): A trial emulation study design.

Background And Aims: Primary biliary cholangitis (PBC) is a rare, progressive liver disease. Obeticholic acid (OCA) received accelerated approval for treating patients with PBC in whom ursodeoxycholic acid (UDCA) failed, based on a surrogate endpoint of reduction in alkaline phosphatase. Analysis of the long-term safety extension with 2 external control groups demonstrated a significant increase in event-free survival in OCA-treated patients.

Early HBcrAg and Anti-HBc Levels Identify Patients at High Risk for Severe Flares After Nucleos(t)ide Analogue Cessation-A Pooled Analysis of Two Clinical Trials.

Background: Severe flares (ALT ≥ 10×ULN) are a well-recognised adverse outcome after nucleos(t)ide analogue (NA) cessation and may lead to liver failure. Thus, identification of patients at risk for these flares is of major importance.

Methods: Data were used from two prospective studies on NA cessation conducted in the Netherlands and Canada.

MASLD, At-Risk MASH and Increased Liver Stiffness Are Associated With Young Adulthood Obesity Without Residual Risk After Losing Obesity.

Background: Obesity can result in persistent metabolic changes despite weight loss, which may affect liver health. We aimed to investigate associations between young adulthood obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), at-risk steatohepatitis and increased liver stiffness measurement (LSM) in a general population setting.

Methods: We studied NHANES 2017-2020 community-dwelling participants aged > 40 years with BMI ≥ 18.

Systemic approaches in biliary tract cancers: a review in the era of multidirectional precision medicine.

Introduction: Despite a rising incidence, biliary tract cancers (BTCs) are still considered a rare tumor entity. The disease's subtle clinical presentation and lack of effective early detection strategies often lead to a diagnosis at an advanced or unresectable stage, where curative options are limited.

Areas Covered: This review provides an overview of current systemic therapies and emerging novel approaches for BTC.

Clinical- and Cost-Effectiveness of Liver Disease Staging in Hepatitis C Virus Infection: A Microsimulation Study.

Background: Liver disease assessment is a key aspect of chronic hepatitis C virus (HCV) infection pre-treatment evaluation but guidelines differ on the optimal testing modality given trade-offs in availability and accuracy. We compared clinical outcomes and cost-effectiveness of common fibrosis staging strategies.

Methods: We simulated adults with chronic HCV receiving care at US health centers through a lifetime microsimulation across five strategies: (1) no staging or treatment (comparator), (2) indirect serum biomarker testing (Fibrosis-4 index [FIB-4]) only, (3) transient elastography (TE) only, (4) staged approach: FIB-4 for all, TE only for intermediate FIB-4 scores (1.

HBV RNA as a Biomarker for Safe Antiviral Discontinuation: A Prospective Study of Nucleos(t)ide Analogue Withdrawal.

Introduction: Withdrawal of nucleos(t)ide analog (NA) therapy is associated with hepatitis B surface antigen (HBsAg) loss and sustained, off-therapy partial cure (normal ALT [≤30 U/L males, ≤20 U/L females) with HBV DNA <2000 IU/mL) but should be offered only to those most likely to benefit. HBVRNA may be useful for risk stratification.

Methods: The Hepatitis B Research Network Immune-Active Trial prospectively evaluated treatment with tenofovir (TDF) for 192 weeks ± peginterferon-α (PegIFN) for initial 24 weeks followed by protocolized withdrawal of TDF amongst eligible participants (NCT01369212).

The burden of cirrhosis and other chronic liver disease in the middle east and North Africa (MENA) region over three decades.

Background: Cirrhosis comprises a significant health challenge in the Middle East and North African (MENA) region impacting healthcare systems and communities. This study sought to investigate trends in the burden of cirrhosis and other chronic liver disease, different etiologies, deaths, and the disability burden utilizing data from the Global Burden of Disease (GBD) database.

Methods: Analyzing epidemiological trends from 1990 to 2021 across 21 MENA countries, this research utilized data on age-standardized incidence rates (ASIR), age-standardized death rates, and age-standardized disability-adjusted life years (DALYs) to evaluate the burden of cirrhosis and other chronic liver disease.

Managing Select Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitors.

The increased use of immune checkpoint inhibitors (ICIs) across cancer programs has created the need for standardized monitoring and management of immune-related adverse events (irAEs). Delayed recognition without appropriate treatment can have serious and life-threatening consequences. The management of irAEs presents a unique set of challenges that must be addressed at a multidisciplinary level.

Embryonic macrophages support endocrine commitment during human pancreatic differentiation.

Organogenesis is a complex process that relies on a dynamic interplay between extrinsic factors originating from the microenvironment and tissue-specific intrinsic factors. For pancreatic endocrine cells, the local niche consists of acinar and ductal cells as well as neuronal, immune, endothelial, and stromal cells. Hematopoietic cells have been detected in human pancreas as early as 6 post-conception weeks, but whether they play a role during human endocrinogenesis remains unknown.

An evolutionary concept analysis: stigma among women living with hepatitis C.

Background: Stigma is a complex social phenomenon that leads to marginalization and influences the course of illness. In the context of hepatitis C virus (HCV), stigma is a well-documented barrier to accessing care, treatment, and cure. In recent years, HCV rates among women have increased, resulting in an urgent need to address stigma and its harmful effects.

Graft Steatosis and Donor Diabetes Mellitus Additively Impact on Recipient Outcomes After Liver Transplantation-A European Registry Study.

Background And Aims: Biopsy-proven severe graft steatosis is associated with adverse outcomes after liver transplantation. The concomitant presence of metabolic risk factors might further increase this risk. We studied the association between graft steatosis and metabolic risk factors in the donor, with recipient outcomes after liver transplantation.

COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls.

Introduction: Obeticholic acid (OCA) treatment for primary biliary cholangitis (PBC) was conditionally approved in the phase 3 POISE trial. The COBALT confirmatory trial assessed whether clinical outcomes in patients with PBC improve with OCA therapy.

Methods: Patients randomized to OCA (5-10 mg) were compared with placebo (randomized controlled trial [RCT]) or external control (EC).

Incidence and prevalence of primary biliary cholangitis in the Netherlands - A nationwide cohort study.

Background & Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS).

Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals.

Severe Cholestasis Predicts Recurrent Primary Sclerosing Cholangitis Following Liver Transplantation.

Background Aims: Primary sclerosing cholangitis (PSC) may reoccur following liver transplantation (LT) and the diagnosis established once imaging studies demonstrate the diagnostic cholangiographic appearance. To evaluate whether the development of recurrent PSC (rPSC) is associated with cholestasis soon after LT, we studied whether changes in hepatic biochemistry within the first 12 months were linked with the development of rPSC and graft loss.

Methods: We conducted a retrospective cohort analysis of 158 transplant recipients with PSC in Canada, and 549 PSC transplant recipients from the United Kingdom.

Ex Vivo Fluorescent Labeling of HBV-Specific B Cells in Chronic Hepatitis B Patients.

Fluorescently conjugated antigen-bait systems have been extensively used to identify antigen-specific B cells and probe humoral immunity across different settings. Following this approach, we used HBV antigens to bind the B cell receptor (BCR), permitting antigen-specific B cell detection by flow cytometry. Fluorochromes can either be attached covalently via chemical conjugation to the antigen or attached non-covalently by biotinylating the antigen.

Optimized Ex Vivo Fluorospot Assay to Measure Multifunctional HBV-Specific T Cell Frequencies in Chronic Hepatitis B Patients.

Virus-specific T cells are critical to mediating viral control; however, Hepatitis B virus (HBV)-specific T cells among chronic Hepatitis B (CHB) patients are functionally exhausted. The inability to consistently measure the ex vivo functionality of HBV-specific T cells has prevented meaningful analysis during antiviral events such as HBeAg seroconversion, hepatic flares, and HBsAg loss. We optimized the traditional IFN-γ ELISpot assay to measure total ex vivo HBV-specific T cell frequencies using CHB PBMCs stimulated with HBV overlapping peptide (OLP) pools.