Background and Aims: Many patients with hepatocellular carcinoma (HCC) present inadequate responses to lenvatinib therapy. Therefore, it is important to elucidate the underlying mechanisms of resistance and to formulate effective reversal strategies. Methods: We conducted comprehensive transcriptome and proteome sequencing analyses of lenvatinib-resistant cell lines and patient tissues to identify

Metabolic dysfunction-associated steatotic liver diseases (MASLD) encompass a spectrum of liver disorders primarily defined by hepatic steatosis and cardiometabolic risk factors. MASLD affects over 30% of the global adult population, representing a substantial risk for public health. MASLD can progress from simple steatosis to steatohepatitis (termed MASH) marked by inflammation and fibrosis, potentially

Background and Aims: Thermal ablation is the standard of care treatment modality with curative intent for early-stage non-resectable hepatocellular carcinoma (HCC), but a durable response is limited—with up to 40% of HCC patients eventually experiencing local recurrence on post-treatment surveillance. While thermal ablation has been established to cause immediate cell death in the center of the thermal

The immune-tolerant (IT) phase of chronic hepatitis B (CHB) is a distinct stage of infection, characterized by high hepatitis B virus (HBV) replication, normal alanine aminotransferase (ALT) levels, and minimal liver inflammation. Despite its classification as a benign phase, growing evidence challenges this notion, revealing immune activation, HBV DNA integration, and potential oncogenic processes

Chromosome 8q amplification is a frequent event in cancers including hepatocellular carcinoma (HCC). TATA-box binding protein Associated Factor 2 (TAF2), a component of Transcription Factor IID (TFIID) residing in 8q24.12, is amplified in HCC. As yet, a potential oncogenic function of TAF2 in HCC has not been documented. We identified TAF2 mRNA and protein overexpression in human HCC cells and tissue

Background: The succinate receptor GPR91 is highly expressed in hepatic stellate cells (HSCs), with its expression further elevated during metabolic-dysfunction-associated steatohepatitis (MASH)-induced fibrotic progression. However, convincing in vivo data on whether blocking GPR91 signaling leads to fibrotic regression in MASH is lacking. Methods: MASH models were induced by choline-deficient amino

Advanced liver fibrosis and ‘At-Risk’ metabolic dysfunction-associated steatohepatitis (At-Risk MASH) is present in 5% and 10% respectively of community based patients with steatotic liver disease (SLD) and metabolic risk factors and/or excess alcohol consumption. Identification of these patients is critical to guide prognosis and management due to their increased risk of liver decompensation and hepatocellular

Background and Aims: In the global, Phase 3 HIMALAYA study in unresectable hepatocellular carcinoma (HCC), STRIDE significantly improved overall survival (OS) versus sorafenib; durvalumab was noninferior to sorafenib. Immune checkpoint inhibitor studies have shown an association between the occurrence of immune-mediated adverse events (imAEs) and improved OS. We assessed potential associations between

Background and Aims: Extracellular matrix protein 1 (ECM1) is known to inhibit transforming growth factor β (TGF-β) signalling and hepatic stellate cells (HSCs) activation, thereby attenuating liver fibrosis. RNA-seq profiling of livers from wild-type (WT) and Ecm1-deficient mice revealed different enrichments in metabolic changes in fatty acid synthesis and inflammatory pathways, suggesting a regulatory

Background: The MASH Resolution Index and FibroScan-aspartate aminotransferase (FAST) score have been reported to non-invasively predict the resolution of metabolic dysfunction-associated steatohepatitis (MASH) on histology. This study aimed to examine head-to-head the diagnostic accuracy of the MASH Resolution Index (MASHResInd) versus FAST score in detecting MASH resolution. Methods: This prospective

The mechanisms that govern postnatal hepatocyte differentiation and maturation in the periportal region, where Notch signaling is high, remain incompletely understood. Here we demonstrate that 2-week-old mice deficient in lymphocytes, CD4+ T cells or T-bet+ regulatory T (Treg) cells exhibit comparable increases in ductal plate cell/cholangiocyte differentiation and impaired periportal hepatocyte maturation

Background and Aims: Liver fibrosis involves the activation of hepatic stellate cells (HSCs) and persistent inflammatory responses. Ccl9, a CC chemokine implicated in inflammation, has an undefined role in liver homeostasis. Our study investigates this murine homolog of human CCL15 to elucidate its role in the development of liver fibrosis. Approach and Results: We investigated the expression of Ccl9

Background & Aims: Research on metabolic reprogramming in hepatocellular carcinoma (HCC) has increased; however, studies on the metabolism of glycerolipids or interactions between different pathways remain scarce. Enzymes of glycerol phosphate dehydrogenase (GPD) family, which regulate glycerol-3-phosphate shuttle, link the metabolic processes of glycolysis and glycerolipids. Therefore, we aimed to

Hepatic stellate cells (HSCs) represent a highly heterogeneous mesenchymal cell population with multifaceted roles in liver homeostasis and disease. Beyond their well-established roles in vitamin A storage and scar formation, there is increasing evidence for HSCs in the regulation of hepatic metabolism, regeneration, immunity and carcinogenesis. Here, we will review the heterogeneity of HSCs in the

Background: Screening for liver disease in the general population requires accurate non-invasive tests (NITs). A head-to-head comparison of NITs for early detection of clinically relevant liver disease among the target population for screening is lacking. Methods: Among meta-cohort (Rotterdam Study and NHANES) with metabolic dysfunction aged 18-80 years, 10 NITs were investigated. The diagnostic accuracy

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), affects approximately 30% of adults worldwide. Approximately 1/6 of MASLD patients progress to metabolic dysfunction-associated steatohepatitis (MASH) and potentially evolve towards cirrhosis and hepatocellular carcinoma (HCC). This condition imposes a significant burden on

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world’s population and is associated with multisystemic comorbidities. We combined multidimensional OMICs approaches to explore the feasibility of using high-throughput targeted circulating proteomics to track systemic organ damage and infer the underlying molecular mechanisms. Methods: We evaluated

Background: Covert hepatic encephalopathy (CHE) is clinically underrecognized. Using MRI, we explored the relationship between functional connectivity as a marker of executive dysfunction and the blood-brain barrier permeability marker KTRANS in a cross-sectional cohort of covert HE (CHE), no HE (NHE), and healthy controls (HC). Methods: This study was a single-center prospective cohort study conducted

Background and Aims: Alcohol-associated steatohepatitis (ASH), a severe form of alcohol-associated liver disease (ALD), is characterized by pronounced steatosis and immune cells infiltration. As an inflammatory disease, ASH still lacks effective immunotherapies, and the mechanisms underlying alcohol-induced immune imbalance in the liver microenvironment remain elusive. RNA modifications are known to

Given the high prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in children and its distinct epidemiological, clinical, and histopathological differences from adult disease, the American Association for the Study of Liver Diseases (AASLD) commissioned this pediatric-focused evidence-based practice statement. A multidisciplinary writing group—encompassing expertise in pediatric

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in children, but its long-term outcomes are poorly understood. This study aimed to quantify mortality rates, identify causes of death, and evaluate the incidence of cirrhosis and extrahepatic outcomes in children with pediatric-onset MASLD. Approach & Results: The Longitudinal

Background & Aims: Hepatic fiber morphology may significantly enhance our understanding of molecular alterations in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to comprehensively characterize hepatic fiber morphological phenotypes in MASLD and their associated molecular alterations using multi-layer omics analyses. Approach & Results: To quantify the morphological phenotypes

Background and Aims: Identifying individuals with compensated advanced chronic liver disease (cACLD) at risk of decompensation allows for personalized therapy. However, predicting decompensation is challenging, and multiple models have been developed. This study systematically appraises the performance and clinical applications of published multivariable models predicting first decompensation in patients

Background & Aims: The outcomes and benefits of antiviral therapy in patients with indeterminate phase HBeAg-negative chronic hepatitis B (CHB) are not well described in treatment guidelines. We examined hepatocellular carcinoma (HCC) risk among these patients. Approach & Results: We identified all non-cirrhotic treatment-naïve patients with HBeAg-negative CHB who received ≥1 test for hepatitis B virus