Background: HCC incidence is increasing worldwide due to the obesity epidemic, which drives metabolic dysfunction-associated steatohepatitis (MASH) that can lead to HCC. However, the molecular pathways driving MASH-HCC are poorly understood. We have previously reported that male mice with haploinsufficiency of hypoxia-associated factor, HAF (SART1 +/-) spontaneously develop MASH-HCC. However, the cell

Background & Aims: Partial hepatectomy (PHx)-induced liver regeneration causes the increase in relative blood flow rate within the liver, which dilates hepatic sinusoids and applies mechanical stretch on liver sinusoidal endothelial cells (LSECs). Heparin-binding EGF-like growth factor (HB-EGF) is a crucial growth factor during liver regeneration. We aimed to investigate whether this sinusoidal dilation-induced

Background and Aims: Hexokinases (HKs), a group of enzymes catalyzing the first step of glycolysis, have been shown to play important roles in liver metabolism and tumorigenesis. Our recent studies identified HKDC1 as a top candidate associated with liver cancer metastasis. We aimed to compare its cell type specificity with other HKs upregulated in liver cancer and investigate the molecular mechanisms

Background/Aims: Resmetirom, liver directed thyroid-hormone receptor-β agonist, received approval for MASH treatment. We assessed HRQL in MASH patients treated with resmetirom. Methods: Non-cirrhotic MASH/NASH patients with confirmed/suspected fibrosis were enrolled in a 54-month double-blind randomized placebo-controlled Phase 3 clinical trial with serial biopsy assessments (MAESTRO-NASH, NCT03900429)

Cholangiopathies comprise a spectrum of chronic intra- and extrahepatic biliary tract disorders culminating in progressive cholestatic liver injury, fibrosis and often cirrhosis and its sequela. Treatment for these diseases is limited and collectively they are one of the therapeutic “black boxes” in clinical hepatology. The etiopathogenesis of the cholangiopathies likely includes disease-specific mediators

Background and Aims: A limited number of drugs are used as standard or alternative therapies in autoimmune hepatitis (AIH). No specific-recommendations are available for patients failing to respond to these therapies. We analyzed the efficacy and safety of infliximab in patients with AIH. Approach and Results: We performed a retrospective study of 42 patients with AIH who received infliximab at 21

Primary sclerosing cholangitis (PSC) is a chronic inflammatory progressive cholestatic liver disease. Genetic risk factors, presence of autoantibodies, the strong clinical link with inflammatory bowel disease (IBD), and associations with other autoimmune disorders all suggest a pivotal role for the immune system in PSC pathogenesis. In this review, we provide a comprehensive overview of recent immunobiology

Background and Aim: Several symptomatic cases of hepatitis E virus (HEV) infections were reported to the New Caledonia Island Public Health Service between August and December 2023. This prompted epidemiological and virological investigations to identify the source of infection. Approach and Results: HEV RNA was assessed in symptomatic patients, various food items and pig farms on the island. HEV strains

Background & Aims: Metabolic dysfunction-associated fatty liver disease (MASLD) is the most prevalent chronic liver pathology in western countries, with serious public health consequences. Efforts to identify causal genes for MASLD have been hampered by the relative paucity of human data from gold-standard magnetic resonance quantification of hepatic fat. To overcome insufficient sample size, genome-wide

Background and Aims: TM6SF2 rs58542926 (E167K) is related to increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Conflicting mouse study results highlight the need for a human model to understand this mutation’s impact. This study aims to create and characterize a reliable human in vitro model to mimic the effects of the TM6SF2-E167K mutation for future studies

Background & Aims: The primary cilium, an organelle that protrudes from cell surfaces, is essential for sensing extracellular signals. With disturbed cellular communication and chronic liver pathologies, this organelle’s dysfunctions have been linked to disorders, including polycystic liver disease (PLD) and Cholangiocarcinoma (CCA). The goal of this study was to elucidate the relationship between

Background & Aims: Biliary Atresia (BA) is a devastating fibro-inflammatory biliary disease that is the leading indication for pediatric liver transplants worldwide. Although cholangiocytes are the primary target cells, the pathogenic mechanisms involving cholangiocytes remain elusive. Here, we aimed to characterize the pathogenic role of cholangiocytes in BA. Approach & Results: Integration of single-cell

Background & Aims: The HFE p.C282Y+/+ (homozygous) genotype and central adiposity both increase liver disease and diabetes risks, but combined effects are unclear. We estimated waist-to-hip ratio (WHR) associations with incident clinical outcomes in routine care in p.C282Y+/+ participants in the UK Biobank community cohort. Approach & Results: Baseline WHR in 1,297 male and 1,602 female p.C282Y+/+

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) management guidelines have been published worldwide; we aimed to summarize, categorize and compare their lifestyle intervention recommendations. Approach & Results: We searched MASLD/nonalcoholic fatty liver disease (NAFLD) management guidelines published between 1 January 2013 and 31 June 2024 via databases including

Background and Aims: Simultaneous inhibition of the TGF-β and PD-L1 pathways provides a potential novel treatment approach. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β “trap”) fused to a human IgG1 monoclonal antibody blocking PD-L1, was evaluated in patients with advanced HCC. Approach and Results: In this global, open-label

Cholestatic drug-induced liver injury is an important and frequently challenging differential diagnosis in patients presenting with elevated liver tests with predominant elevation in alkaline phosphatase (ALP). A number of competing etiologies need to be ruled out, such as hepatobilary malignancy, choledocholithiasis, cholestatic forms of viral hepatitis, cholestasis of sepsis, primary and secondary

Background & Aims: Non-invasive biomarkers provide prognostic information for the development of major adverse liver outcomes (MALO) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the predictive value of longitudinal biomarker measurements has not been evaluated. We assessed whether changes in biomarkers could predict incident MALO in MASLD. Approach and Results:

Background & Aims: The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and risk of MASLD and its severity. Approach

Background and Aims: The chemical carcinogen diethylnitrosamine (DEN) is often used to induce hepatocellular carcinoma (HCC) in mice. Curiously, several labs have reported that removal of oncoproteins from hepatocytes exacerbated DEN-induced HCC, with mechanisms unknown. This study aimed at deciphering molecular mechanisms underlying the tumor suppressive effect of oncoproteins. Methods and Results:

Multidisciplinary clinics (MDCs) are gaining momentum throughout the medical field, having initially been pioneered in oncology clinics, due to their inherent ability to streamline complex care and improve both patient outcomes and the patient care experience. Liver transplant and hepatobiliary tumor clinics are examples of established MDCs in hepatology. With the changing landscape of liver disease

Background and Aims: After extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs via transdifferentiation of biliary epithelial cells (BECs), which involves dedifferentiation of BECs into bipotential progenitor cells (BP-PCs) and subsequent redifferentiation of BP-PCs into nascent hepatocytes and BECs. Despite several studies on the redifferentiation process of BP-PCs

BACKGROUND AND AIMS Alcohol-associated hepatitis (AH) is a clinically severe, acute disease that afflicts only a fraction of patients with alcohol use disorder (AUD). Genomic studies of alcohol-associated cirrhosis (AC) have identified several genes of large effect, but the genetic and environmental factors that lead to AH and AC, and their degree of genetic overlap, remain largely unknown. This study

Background and Aims: Chronic liver disease due to metabolic dysfunction–associated steatohepatitis (MASH) is a rapidly increasing global epidemic. MASH progression is a consequence of the complex interplay between inflammatory insults and dysregulated hepatic immune responses. T lymphocytes have been shown to accumulate in the liver during MASH, but the cause and consequence of T cell accumulation

Background & Aims: Offering LT to frail patients may reduce waitlist mortality but may increase post-LT mortality. LT survival benefit is the concept of balancing these risks. We sought to quantify net survival benefit with LT by liver frailty index (LFI). Approach & Results: We analyzed data in the multi-center Functional Assessment in LT (FrAILT) Study from 2012-2021. Pre-LT cohort included ambulatory

Background and Aims: Liver fibrosis represents a global health burden, given the paucity of approved antifibrotic therapies. Liver sinusoidal endothelial cells (LSECs) play a major gatekeeping role in hepatic homeostasis and liver disease pathophysiology. In early tumorigenesis, runt-related transcription factor 3 (RUNX3) functions as a sentinel; however, its function in liver fibrosis in LSECs remains

BACKGROUND AND AIMS In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial. APPROACH AND RESULTS Data from 147 participants in a multicenter randomized clinical

BACKGROUND AND AIMS There are limited data on the progression of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in people with type 2 diabetes mellitus (T2DM) versus those without T2DM in biopsy-proven metabolic dysfunction-associated steatotic liver disease. We examined LSM progression in participants with T2DM versus those without T2DM in a large, prospective

■: Disruption of the epigenome is a hallmark of human disease including liver cirrhosis and hepatocellular carcinoma (HCC). While genetic heterogeneity is an established effector of pathologic phenotypes, epigenetic heterogeneity is less well understood. Environmental exposures alter the liver-specific DNA methylation landscape and influence the onset of liver cancer. Given that currently available

Background and Aims: Hepatic stellate cells (HSCs) contribute to hepatocellular carcinoma (HCC) progression by regulating multiple factors. However, the entire immunoregulatory functions of HSCs are still obscure. Here, we aim to investigate whether HSCs impose CX3CR1+ macrophages to pro-tumorigenic properties in the peritumoral area. Approach and Results: In single cell RNA-sequencing analysis of

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent pediatric liver disease, yet accurate risk scores for referral of children/adolescents with suspected clinically significant liver fibrosis are currently lacking. Approach & Results: Clinical and biochemical variables were collected in a prospective cohort of 327 children and adolescents with severe

Background&aims: Unlike other malignancies, hepatic functional reserve competes with tumour progression in determining the risk of mortality from hepatocellular carcinoma (HCC). However, the relative contribution of hepatic decompensation over tumour progression in influencing overall survival (OS) has not been assessed in combination immunotherapy recipients. Approach&Results: From the AB-real observational

Background and aims: The liver possesses a remarkable regenerative capacity in response to injuries or viral infections. Various growth factors and cytokines are involved in regulating liver regeneration. Prostaglandin (PG) D2, a pro-resolution lipid mediator, is the most abundant hepatic prostanoid. However, the role of PGD2 in the injury-induced liver regeneration remains unclear. Approach and results:

Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. Dynamic changes in magnetic resonance imaging (MRI) proton-density-fat fraction (PDFF) are associated with MASH resolution. We aimed to determine the relative efficacy of therapeutic agents for reducing hepatic fat, assessed by magnetic resonance imaging (MRI) proton-density-fat fraction

DILI frequently contributes to the attrition of new drug candidates and is a common cause for the withdrawal of approved drugs from the market. Although some noncytochrome P450 (non-CYP) metabolism enzymes have been implicated in DILI development, their association with DILI outcomes has not been systematically evaluated. In this study, we analyzed a large data set comprising 317 drugs and their interactions