Serum protein risk stratification score for diagnostic evaluation of metabolic dysfunction-associated steatohepatitis.

Background: Reliable, noninvasive tools to diagnose at-risk metabolic dysfunction-associated steatohepatitis (MASH) are urgently needed to improve management. We developed a risk stratification score incorporating proteomics-derived serum markers with clinical variables to identify high-risk patients with MASH (NAFLD activity score >4 and fibrosis score >2).

Methods: In this 3-phase proteomic study of biopsy-proven metabolic dysfunction-associated steatotic fatty liver disease, we first developed a multi-protein predictor for discriminating NAFLD activity score >4 based on SOMAscan proteomics quantifying 1305 serum proteins from 57 US patients.

Deep Learning Based Shear Wave Detection and Segmentation Tool for Use in Point-of-Care for Chronic Liver Disease Assessments.

Objective: As metabolic dysfunction-associated steatotic liver disease (MASLD) becomes more prevalent worldwide, it is imperative to create more accurate technologies that make it easy to assess the liver in a point-of-care setting. The aim of this study is to test the performance of a new software tool implemented in Velacur (Sonic Incytes), a liver stiffness and ultrasound attenuation measurement device, on patients with MASLD. This tool employs a deep learning-based method to detect and segment shear waves in the liver tissue for subsequent analysis to improve tissue characterization for patient diagnosis.

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.

The Use of Noninvasive Velacur® for Discriminating between Volunteers and Patients with Chronic Liver Disease: A Feasibility Study.

Background And Aims: Nonalcoholic fatty liver disease is the leading cause of chronic liver disease globally and can progress to cirrhosis, liver failure, and liver cancer. Current AASLD, AGA, and ADA guidelines recommend assessment for liver fibrosis in all patients with NAFLD. Serum biomarkers for fibrosis, while widely available, have notable limitations.

Case report and mini-review: Sarcina ventriculi in the stomach of an 80-year-old female.

Sarcina ventriculi, also known as Zymosarcina ventriculi and, incorrectly, as Clostridium ventriculi, is rarely encountered in clinical settings. A patient with a complicated gastrointestinal (GI) history, who was acutely presenting with small-bowel obstruction, was found to be colonized by S. ventriculi.

Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis.

Objective: In retrospective studies, liver stiffness (LS) by vibration-controlled transient elastography (VCTE) is associated with the risk of liver decompensation in patients with non-alcoholic steatohepatitis (NASH), but prospective data in biopsy-confirmed cohorts with advanced fibrosis are limited. We aimed to establish thresholds for LS by VCTE that predict progression to cirrhosis among patients with bridging fibrosis and hepatic decompensation among patients with cirrhosis due to NASH.

Design: We used data from four randomised placebo-controlled trials of selonsertib and simtuzumab in participants with advanced fibrosis (F3-F4).

A phase 2, open-label, randomized, multiple-dose study evaluating Inarigivir in treatment-naïve patients with chronic hepatitis B.

Background/aims: Novel agents acting against hepatitis B virus (HBV) are needed to improve HBsAg seroclearance or termed as 'functional cure'. Inarigivir (retinoic acid-inducible gene I agonist) has immunomodulatory and direct antiviral actions against HBV. We aimed to determine the safety and efficacy of Inarigivir for the treatment of HBV infection.

First-line therapies for hepatitis B in the United States: A 3-year prospective and multicenter real-world study after approval of tenofovir alefenamide.

Real-world data are limited on tenofovir alafenamide (TAF). We aimed to study TAF real-world outcomes with other first-line regimens for chronic hepatitis B (CHB). We enrolled patients with CHB from 10 centers retrospectively and followed them for 36 months prospectively.

Fibrosis-4 Index Can Independently Predict Major Adverse Cardiovascular Events in Nonalcoholic Fatty Liver Disease.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is closely associated with an increased risk of cardiovascular disease. We aimed to determine whether the fibrosis-4 index (FIB-4) can identify patients with NAFLD at highest risk of cardiovascular events.

Methods: We analyzed data from 81,108 patients with (i) a diagnosis of NAFLD, (ii) nonalcoholic steatohepatitis (NASH), or (iii) at risk (RISK) of NASH.

Fibrosis-4 Index as an Independent Predictor of Mortality and Liver-Related Outcomes in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and its prevalence continues to rise. Fibrosis-4 index (FIB-4) has been shown to be a prognostic marker of liver-related outcomes in patients with NAFLD. We analyzed data from TriNetX global federated research network, combining data on 30 million patients.

Adenosine deaminase 2 produced by infiltrative monocytes promotes liver fibrosis in nonalcoholic fatty liver disease.

Elevated circulating activity of adenosine deaminase 2 (ADA2) is associated with liver fibrosis in nonalcoholic fatty liver disease (NAFLD). In the liver of NAFLD patients, ADA2-positive portal macrophages are significantly associated with the degree of liver fibrosis. These liver macrophages are CD14- and CD16-positive and co-express chemokine receptors CCR2, CCR5, and CXCR3, indicating infiltrative monocyte origin.

Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis.

Background And Aims: Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests (NITs) of fibrosis with liver-related complications in patients with NASH cirrhosis.

Approach And Results: Patients with compensated cirrhosis due to NASH were enrolled in two placebo-controlled trials of simtuzumab and selonsertib.

Lipoprotein Z, a hepatotoxic lipoprotein, predicts outcome in alcohol-associated hepatitis.

Background And Aims: Lipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched LDL-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcohol-associated hepatitis (AH) and interrogate the biology behind its formation.

Approach And Results: We measured serum levels of LP-Z using nuclear magnetic resonance spectroscopy, a well-established clinical assay.

A Machine Learning Approach to Liver Histological Evaluation Predicts Clinically Significant Portal Hypertension in NASH Cirrhosis.

Background And Aims: The hepatic venous pressure gradient (HVPG) is the standard for estimating portal pressure but requires expertise for interpretation. We hypothesized that HVPG could be extrapolated from liver histology using a machine learning (ML) algorithm.

Approach And Results: Patients with NASH with compensated cirrhosis from a phase 2b trial were included.

A Dynamic Aspartate-to-Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease.

The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death.

Prevalence of drug-drug interactions with pangenotypic direct-acting antivirals for hepatitis C and real-world care management in the United States: a retrospective observational study.

: Direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) have varying potentials for drug-drug interactions (DDIs). To (1) identify prevalence of potential DDI with glecaprevir-pibrentasvir (GLE-PIB) and sofosbuvir-velpatasvir (SOF-VEL) and (2) describe health care provider actions in response to pharmacist recommendations based on potential interactions with GLE-PIB or SOF-VEL, using 2 complementary data sources. Possible interacting drugs were identified among adult patients in a United States electronic medical record database covering 21 health care organizations and 26 million patients in 2018.

Differential Associations of Circulating MicroRNAs With Pathogenic Factors in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disease driven by genetic and environmental factors. MicroRNAs (miRNAs) serve as pleiotropic post-transcriptional regulators of cellular pathways. Although several miRNAs have been associated with NAFLD and fibrosis, there are limited studies in humans examining their differential association with pathogenic factors or histological features of NAFLD.

Three Years of Progress Toward Achieving Hepatitis C Elimination in the Country of Georgia, April 2015-March 2018.

Background: In April 2015, in collaboration with the US Centers for Disease Control and Prevention and Gilead Sciences, the country of Georgia embarked on the world's first hepatitis C elimination program. We aimed to assess progress toward elimination targets 3 years after the start of the elimination program.

Methods: We constructed a hepatitis C virus (HCV) care cascade for adults in Georgia, based on the estimated 150 000 persons aged ≥18 years with active HCV infection.

Changing demographics among populations prescribed HCV treatment, 2013-2017.

Objectives: We analyzed the demographics and disease characteristics of patients prescribed treatment for chronic hepatitis C virus (HCV) infection from 2013 through 2017, a time frame that encompasses the expansion of available direct-acting antiviral inhibitors.

Study Design: Retrospective analysis.

Methods: Using a proprietary disease-management program, data for 19,944 patients receiving HCV treatment were collected from providers and specialty pharmacies.

Noninvasive Tests Accurately Identify Advanced Fibrosis due to NASH: Baseline Data From the STELLAR Trials.

Accurate noninvasive tests (NITs) are needed to replace liver biopsy for identifying advanced fibrosis caused by nonalcoholic steatohepatitis (NASH). We analyzed screening data from two phase 3 trials of selonsertib to assess the ability of NITs to discriminate advanced fibrosis. Centrally read biopsies from the STELLAR studies, which enrolled patients with bridging fibrosis and compensated cirrhosis, were staged according to the NASH Clinical Research Network classification.

Safety and effectiveness of lusutrombopag in Japanese chronic liver disease patients with thrombocytopenia undergoing invasive procedures: Interim results of a postmarketing surveillance.

Aim: Lusutrombopag is approved for the treatment of thrombocytopenia in chronic liver disease patients undergoing invasive procedures. This real-world surveillance assesses the safety and effectiveness of lusutrombopag in Japan.

Methods: This ongoing, multicenter, prospective, real-world surveillance is collecting data from case report forms between October 2016 and May 2021.

Liver Fibrosis Determination.

All chronic liver disease can lead to liver fibrosis. Assessment of the severity of liver fibrosis is central to making treatment and management decisions. Liver biopsy, the gold standard for liver fibrosis assessment, is invasive and carries risks of complications and sampling errors.