Mendelian Randomization has become a popular tool to assess causal relationships using existing observational data. While randomized controlled trials are considered the gold standard for establishing causality between exposures and outcomes, it is not always feasible to conduct a trial. Mendelian Randomization is a causal inference method that uses observational data to infer causal relationships

BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD), comprises a spectrum of liver disorders with the initial abnormal accumulation of lipids in hepatocytes called nonalcoholic fatty liver (NAFL), progressing to the more serious non-alcoholic steatohepatitis (NASH) in a subset of individuals. Our previous study revealed that global flavin-containing monooxygenase 2 (FMO2) knockout causes higher

BACKGROUND AIMS The hallmark of nonalcoholic fatty liver disease (NAFLD) or hepatic steatosis is characterized by lipid droplet (LD) accumulation in hepatocytes. Autophagy may have profound effects on lipid metabolism and innate immune response. However, how innate immune activation may regulate the autophagic degradation of intracellular LDs remains elusive. APPROACH RESULTS A mouse model of a high-fat

BACKGROUND AIMS The liver has a remarkable capacity to regenerate, which is sustained by the ability of hepatocytes to act as facultative stem cells that, while normally quiescent, re-enter the cell cycle after injury. Growth factor signaling is indispensable in rodents, whereas Wnt/β-catenin is not required for effective tissue repair. However, the molecular networks that control human liver regeneration

BACKGROUND AIMS Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease worldwide but only a subset of NAFLD individuals may progress to nonalcoholic steatohepatitis (NASH). While NASH is an important etiology of hepatocellular carcinoma (HCC), the underlying mechanisms responsible for conversion of NAFLD to NASH, and then to HCC are poorly understood. We aimed to identify

BACKGROUND AIMS Studies have suggested that patients with chronic hepatitis B (CHB), either co-, or super infected, have more aggressive liver disease progression than those with the hepatitis delta virus (HDV). This systematic literature review and meta-analysis examined whether HDV RNA status is associated with increased risk of advanced liver disease events (ALDEs), in patients who are HBsAg and

BACKGROUND AND AIMS Liver fibrosis is common in children with nonalcoholic fatty liver disease (NAFLD) and an important determinant of outcomes. High performing non-invasive models to assess fibrosis in children are needed. The objectives of this study were to evaluate the performance of existing pediatric and adult fibrosis prediction models and to develop a clinical prediction rule for identifying

BACKGROUND AIMS We aim to assess the role of radiological response to atezolizumab-bevacizumab (AtezoBev) in patients with hepatocellular carcinoma (HCC) to predict overall survival (OS). APPROACH RESULTS We retrospectively included HCC patients treated by AtezoBev in two tertiary centers. A retrospective blinded analysis was performed by two radiologists to assess RECIST1.1 and mRECIST criteria at

BACKGROUND AND AIMS Recently, the American Gastroenterological Association (AGA) and American Association for the Study of Liver Diseases (AASLD) developed clinical pathways to evaluate populations at high-risk for nonalcoholic fatty liver disease (NAFLD). We assessed the diagnostic performance of the new guidance in a well-phenotyped cohort of patients with Type 2 diabetes mellitus (T2DM). APPROACH

Alcohol use disorder (AUD) remains a significant public health concern, affecting around 5% of adults worldwide. Novel pathways of damage have been described during the last years, providing insight into the mechanism of injury due to alcohol misuse beyond the direct effect of ethanol byproducts on the liver parenchyma and neurobehavioral mechanisms. Thus, the gut-liver-brain axis and immune system

BACKGROUND AIMS Hepatocellular carcinoma (HCC) is closely associated with inflammation and immune modulation, and combined chemotherapy with other strategies is under extensive investigation to achieve better efficacy. HCC is accompanied by zinc deficiency. This study aims to understand how zinc could affect macrophage function and its application for HCC therapy. APPROACH RESULTS Zn2+ and the zinc

BACKGROUND International regulatory agencies recommend testing drug therapy for patients with noncirrhotic high-risk metabolic dysfunction-associated steatohepatitis (MASH) because they are at risk of liver-related events(LRE). We aimed to compare the risk of LRE in MASLD patients stratified for F2-F4 fibrosis and MASH. METHODS 1938 consecutive patients with biopsy-proven MASLD were enrolled. High-risk

Excessive alcohol use is a major risk factor for the development of an alcohol use disorder (AUD) and contributes to a wide variety of other medical illnesses, including alcohol-associated liver disease (ALD). Both AUD and ALD are complex and causally inter-related diseases, and multiple factors other than alcohol consumption are implicated in the disease pathogenesis. While the underlying pathophysiology

BACKGROUND AIMS A previous individual patient data meta-analysis (IPD-MA) showed that compared with drugs+endoscopy, placement of transjugular portosystemic shunt within 72 hrs of admission (preemptive TIPS: p-TIPS) increases the survival of high-risk patients (Child-Pugh B+active bleeding and Child-Pugh C<14points) with cirrhosis and acute variceal bleeding (AVB). However, previous IPD-MA was not

BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) surveillance is challenged by the detection of hepatic focal lesions (HFLs) of other types. This study aimed to describe the incidence, characteristics, outcomes and costs of non-HCC HFL detected during surveillance. APPROACH AND RESULTS We retrospectively analyzed non-standardized workup performed in French patients included in HCC surveillance programs

BACKGROUND AND AIMS Aerobic glycolysis reprogramming occurs during HSC activation, but how it is initiated and sustained remains unknown. We investigated the mechanisms by which canonical Wnt signaling regulated HSC glycolysis and the therapeutic implication for liver fibrosis. APPROACH AND RESULTS Glycolysis was examined in HSC-LX2 cells upon manipulation of Wnt/β-catenin signaling. Nuclear translocation

BACKGROUND AND AIMS NASH-HCC is inherently resistant to immune checkpoint blockade, but its tumor immune microenvironment is largely unknown. APPROACH AND RESULTS We applied the imaging mass cytometry to construct a spatially resolved single-cell atlas from the formalin-fixed and paraffin-embedded tissue sections from patients with NASH-HCC, virus-HCC (HBV-HCC and HCV-HCC), and healthy donors. Based

BACKGROUND AND AIMS Aldafermin, an engineered analog of the human hormone FGF19, improves liver histology in patients with non-cirrhotic nonalcoholic steatohepatitis (NASH), however, its efficacy and safety in compensated cirrhosis is unknown. No drug has yet to demonstrate benefit in the compensated NASH population. APPROACH AND RESULTS In this multicenter, double-blind, placebo-controlled, phase

BACKGROUND AND AIMS Hepatopulmonary syndrome (HPS) is a common complication of liver disease defined by abnormal oxygenation and intrapulmonary vascular dilatation, treated with liver transplantation. Little is known about changes in HPS physiological parameters over time. We sought to describe baseline clinical and physiological characteristics in HPS and their relationships, temporal changes in physiological

BACKGROUND AIMS The multisociety consensus nomenclature has renamed non-alcoholic fatty liver disease (NAFLD) to steatotic liver disease (SLD) with various sub-classifications. There is paucity of data regarding how the new nomenclature modifies our understanding of disease prevalence and patient phenotypes. APPROACH RESULTS Using the National Health and Nutrition Examination Survey from 1/2017-3/2020

Hepatoblastoma (HB) is the main paediatric liver cancer, but it is a very rare disease. Despite significant improvements in the treatment of children diagnosed with HB, limited treatment options exist for patients with advanced tumours. Besides, survivors generally have long-term adverse effects derived from treatment such as ototoxicity, cardiotoxicity, delayed growth, and secondary tumours. Accordingly

BACKGROUND AIMS Inherited short telomeres are associated with risk of liver disease, whereas longer telomeres predispose to cancer. The association between telomere length and risk of hepatocellular carcinoma and cholangiocarcinoma remains unknown. APPROACH RESULTS We measured leukocyte telomere length using multiplex PCR in 63,272 individuals from the Danish general population. Telomere length and

Obesity is highly prevalent in hepatology clinics and has significant impact in chronic liver disease and patient management. Hepatologists and gastroenterologist need to be actively engaged in the management of obesity. This review provides a detailed approach to this challenging comorbidity.

Cell death and inflammation play critical roles in chronic tissue damage caused by cholestatic liver injury leading to fibrosis and cirrhosis. Liver cirrhosis is often associated with kidney damage that is a severe complication with poor prognosis. Interferon regulatory factor 3 (IRF3) is known to regulate apoptosis and inflammation, but its role in cholestasis remains obscure. In this study, we discovered

BACKGROUND AND AIMS Scirrhous hepatocellular carcinoma (SHCC) is one of the unique subtypes of hepatocellular carcinoma (HCC), characterized by abundant fibrous stroma in tumor microenvironment. However, it remains unclear about the molecular traits of SHCC, which is essential to develop specialized therapeutic approaches for SHCC. APPROACH RESULTS We presented an integrative analysis containing single-cell

BACKGROUND AIM Prognostic tools or biomarkers are urgently needed in polycystic liver disease (PLD) to monitor disease progression and evaluate treatment outcomes. Total liver volume (TLV) is currently used to assess cross-sectional disease severity and female patients typically have larger livers than males. Therefore, this study explores the sex-specific association between TLV and volume reducing

BACKGROUND AND AIMS The fitness and viability of a tumor ecosystem are influenced by the spatial organization of its cells. We aimed to study the structure, architecture, and cell-cell dynamics of the heterogenous liver cancer tumor microenvironment using spatially resolved multiplexed imaging. APPROACH AND RESULTS We performed co-detection by indexing (CODEX) multiplexed immunofluorescence imaging

Over the past years, there has been a remarkable advance in the systemic treatment options for advanced HCC. The overall survival has gradually increased over time, with larger benefits for patients with sensitive tumors and preserved liver function, the latter being an essential condition for the delivery of sequential lines of treatment and optimization of clinical outcomes. With the approval of

BACKGROUND AND AIMS Immune cells play a crucial role in liver aging. However, the impact of dynamic changes in the local immune microenvironment on age-related liver injury remains poorly understood. We aimed to characterize intrahepatic immune cells at different ages to investigate key mechanisms associated with liver aging. APPROACH AND RESULTS We carried out single-cell RNA sequencing (scRNA-seq)

BACKGROUND AND AIM The International Autoimmune hepatitis (AIH) Group retrospective registry (IAIHG-RR) is a web-based platform with subjects enrolled with a clinical diagnosis of AIH. As prognostic factor studies with enough power are scarce, this study aimed to ascertain data quality and identify prognostic factors in the IAIHG-RR cohort. METHODS This retrospective, observational, multicenter study

BACKGROUND AND AIMS Hyperlipidemia has been extensively recognized as a high-risk factor for non-alcoholic steatohepatitis (NASH); however, clinical susceptibility to NASH is highly heterogeneous. The key controller(s) of NASH susceptibility in patients with hyperlipidemia have not yet been elucidated. Here, we aimed to reveal the key regulators of NASH in patients with hyperlipidemia and to explore

Co-infection with hepatitis B virus (HBV) and hepatitis D virus (HDV) results in hepatitis D, the most severe form of chronic viral hepatitis, frequently leading to liver decompensation and hepatocellular carcinoma. Pegylated interferon alpha, the only treatment option for chronic hepatitis D for many years, has limited efficacy. New treatments are in advanced clinical development, with one recent

BACKGROUND AND AIMS Genetic risk factors are major determinants of chronic liver disease (CDL) progression. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M polymorphism and alpha-1 antitrypsin E342K variant, termed PiZ, are major modifiers of metabolic CLD. Both variants are known to affect metabolic CLD via increased endoplasmic reticulum stress, but their combined effect on

BACKGROUND the role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these patients is scarce. Approach & results: we performed a systematic review and meta-analysis according to PRISMA guidelines on the efficacy of MAUD in patients with cirrhosis. Search was conducted in PubMed, Embase and Scopus