Hepatic FXR-FGF4 is required for bile acid homeostasis via an FGFR4-LRH-1 signal node under cholestatic stress.

Bile acid (BA) homeostasis is vital for various physiological processes, whereas its disruption underlies cholestasis. The farnesoid X receptor (FXR) is a master regulator of BA homeostasis via the ileal fibroblast growth factor (FGF)15/19 endocrine pathway, responding to postprandial or abnormal transintestinal BA flux. However, the de novo paracrine signal mediator of hepatic FXR, which governs the extent of BA synthesis within the liver in non-postprandial or intrahepatic cholestatic conditions, remains unknown.

HIF-2α drives hepatic Kupffer cell death and proinflammatory recruited macrophage activation in nonalcoholic steatohepatitis.

Proinflammatory hepatic macrophage activation plays a key role in the development of nonalcoholic steatohepatitis (NASH). This involves increased embryonic hepatic Kupffer cell (KC) death, facilitating the replacement of KCs with bone marrow-derived recruited hepatic macrophages (RHMs) that highly express proinflammatory genes. Moreover, phago/efferocytic activity of KCs is diminished in NASH, enhancing liver inflammation.

Reproducibility and Repeatability of US Shear-Wave and Transient Elastography in Nonalcoholic Fatty Liver Disease.

Background US shear-wave elastography (SWE) and vibration-controlled transient elastography (VCTE) enable assessment of liver stiffness, an indicator of fibrosis severity. However, limited reproducibility data restrict their use in clinical trials. Purpose To estimate SWE and VCTE measurement variability in nonalcoholic fatty liver disease (NAFLD) within and across systems to support clinical trial diagnostic enrichment and clinical interpretation of longitudinal liver stiffness.

Dynamic pattern of postprandial bile acids in paediatric non-alcoholic fatty liver disease.

Background: Dysregulation of bile acids (BAs), as important signalling molecules in regulating lipid and glucose metabolism, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, static BA profiles during fasting may obscure certain pathogenetic aspects. In this study, we investigate the dynamic alterations of BAs in response to an oral glucose tolerance test (OGTT) among children with NAFLD.

The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints.

Introduction: One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis.

Methods: The LCN consists of a Scientific Data Coordinating Center and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations.

Global Prevalence, Clinical Characteristics, Surveillance, Treatment Allocation, and Outcomes of Alcohol-Associated Hepatocellular Carcinoma.

Background: Although the burden of alcohol-associated hepatocellular carcinoma (HCC) is increasing with rising alcohol consumption, clinical presentation and outcomes of alcohol-associated HCC have not been systematically assessed. We aimed to determine the prevalence, clinical characteristics, surveillance rates, treatment allocation, and outcomes of alcohol-associated HCC.

Methods: Medline and Embase were searched from inception to January 2023.

Association between paravertebral muscle radiological parameter alterations and non-alcoholic fatty liver disease.

Purpose: To assess changes in laboratory indices, paravertebral muscle (PVM) fat infiltration and multi b-value DWI parameters and their potential correlation with NAFLD.

Methods: This retrospective analysis included 178 patients with histopathologically confirmed NAFLD, incluiding 76 with non-alcoholic steatohepatitis (NASH). Differences in PVM fat infiltration ratio (FIR), DWI parameters, and laboratory indices were compared between two groups.

Integrating genetic and socioeconomic data to predict the progression of nonalcoholic fatty liver disease.

Objectives: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally, with an estimated prevalence exceeding 25%. Variants in the PNPLA3 and HSD17B13 genes have been a focus of investigations surrounding the etiology and progression of NAFLD and are believed to contribute to a greater burden of disease experienced by Hispanic Americans. However, little is known about socioeconomic factors influencing NAFLD progression or its increased prevalence among Hispanics.

An Electronic Health Record Model for Predicting Risk of Hepatic Fibrosis in Primary Care Patients.

Background: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease.

Aim: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes.

Methods: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM].

A prospective study on the prevalence of at-risk MASH in patients with type 2 diabetes mellitus in the United States.

Background: There are limited data on the prevalence and treatment of at-risk metabolic dysfunction-associated steatohepatitis (MASH) among patients with type 2 diabetes (T2DM) in the United States.

Aim: To estimate the prevalence of at-risk MASH in a prospectively recruited cohort of adults with T2DM using new nomenclature endorsed by multiple societies.

Methods: This prospective study enrolled adults aged ≥50 with T2DM from primary care and endocrinology clinics in southern California from 2016 to 2023.

Velacur ACE outperforms FibroScan CAP for diagnosis of MASLD.

Background: As the prevalence of metabolic dysfunction-associated steatotic liver disease increases, it is imperative to have noninvasive alternatives to liver biopsy. Velacur offers a non-invasive, point-of-care ultrasound-based method for the assessment of liver stiffness and attenuation. The aim of this study was to perform a head-to-head comparison of liver stiffness and liver fat determined by Velacur and FibroScan using MRI-based measurements as the reference standard.

Aspirin for Metabolic Dysfunction-Associated Steatotic Liver Disease Without Cirrhosis: A Randomized Clinical Trial.

Importance: Aspirin may reduce severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and lower the incidence of end-stage liver disease and hepatocellular carcinoma, in patients with MASLD. However, the effect of aspirin on MASLD is unknown.

Objective: To test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD.

MASH Resolution Index: development and validation of a non-invasive score to detect histological resolution of MASH.

Background: Dynamic changes in non-invasive tests, such as changes in alanine aminotransferase (ALT) and MRI proton-density-fat-fraction (MRI-PDFF), may help to detect metabolic dysfunction-associated steatohepatitis (MASH) resolution, but a combination of non-invasive tests may be more accurate than either alone. We developed a novel non-invasive score, the MASH Resolution Index, to detect the histological resolution of MASH.

Methods: This study included a derivation cohort of 95 well-characterised adult participants (67% female) with biopsy-confirmed MASH who underwent contemporaneous laboratory testing, MRI-PDFF and liver biopsy at two time points.

The future of International Classification of Diseases coding in steatotic liver disease: An expert panel Delphi consensus statement.

Background: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy.

Methods: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries.

The Global Burden of Early-Onset Biliary Tract Cancer: Insight From the Global Burden of Disease Study 2019.

Backgrounds/objectives: The escalating incidence of early-onset gastrointestinal cancers is becoming a primary global health concern. Biliary tract cancer (BTC) has been relatively understudied in this regard. We conducted an epidemiological study regarding the burden of this condition.

Disruption of gut barrier integrity and host-microbiome interactions underlie MASLD severity in patients with type-2 diabetes mellitus.

Aberration of the "gut-liver axis" contributes to the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we use multi-omics to analyze the gut microbiota composition and metabolic profile of patients with type-2 diabetes mellitus (T2DM). T2DM patients were screened for liver disease by blood tests, ultrasound, and liver stiffness measurements.