Advances in non-invasive assessment of hepatic fibrosis.

Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex).

An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis.

Liver cell death has an essential role in nonalcoholic steatohepatitis (NASH). The activity of the energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK) is repressed in NASH. Liver-specific AMPK knockout aggravated liver damage in mouse NASH models.

FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study.

Background: The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS≥4), and advanced fibrosis (stage 2 or higher [F≥2]).

Methods: This prospective study included a derivation cohort before validation in multiple international cohorts.

Assessment of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease by Using Quantitative US.

Background Advanced confounder-corrected chemical shift-encoded MRI-derived proton density fat fraction (PDFF) is a leading parameter for fat fraction quantification in nonalcoholic fatty liver disease (NAFLD). Because of the limited availability of this MRI technique, there is a need to develop and validate alternative parameters to assess liver fat. Purpose To assess relationship of quantitative US parameters to MRI PDFF and to develop multivariable quantitative US models to detect hepatic steatosis and quantify hepatic fat.

Collagen biology and non-invasive biomarkers of liver fibrosis.

There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liver disease (NAFLD). In particular, there is a need for diagnostic and prognostic tools, as well as predictive biomarkers that reflect the efficacy of interventions, as described by the BEST criteria (Biomarkers, EndpointS, and other Tools Resource).

Multicenter Validation of Association Between Decline in MRI-PDFF and Histologic Response in NASH.

Background And Aims: Emerging data from a single-center study suggests that a 30% relative reduction in liver fat content as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) from baseline may be associated with histologic improvement in nonalcoholic steatohepatitis (NASH). There are limited multicenter data comparing an active drug versus placebo on the association between the quantity of liver fat reduction assessed by MRI-PDFF and histologic response in NASH. This study aims to examine the association between 30% relative reduction in MRI-PDFF and histologic response in obeticholic acid (OCA) versus placebo-treated patients in the FLINT (farnesoid X receptor ligand obeticholic acid in NASH trial).

Cenicriviroc Treatment for Adults With Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study.

Background And Aims: Cenicriviroc (CVC) is a C-C chemokine receptors type 2 and 5 dual antagonist under evaluation for treating liver fibrosis in adults with nonalcoholic steatohepatitis (NASH). Year 1 primary analysis of the 2-year CENTAUR study showed that CVC had an antifibrotic effect without impacting steatohepatitis. Herein, we report the final data from year 2 exploratory analyses.

Prospective, Same-Day, Direct Comparison of Controlled Attenuation Parameter With the M vs the XL Probe in Patients With Nonalcoholic Fatty Liver Disease, Using Magnetic Resonance Imaging-Proton Density Fat Fraction as the Standard.

Background & Aims: Controlled attenuation parameter (CAP) measurements using M probe have been reported to be lower than those of the XL-probe in detection of hepatic steatosis. However, there has been no direct comparison of CAP with the M vs the XL probe in patients with nonalcoholic fatty liver disease (NAFLD). We compared CAP with the M vs the XL probe for quantification of hepatic fat content, using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the standard.

The Role of Noninvasive Tests for Differentiating NASH From NAFL and Diagnosing Advanced Fibrosis Among Patients With NAFLD.

Assessing for the presence of non-alcoholic steatohepatitis (NASH) and the presence of advanced fibrosis is vital among patients with non-alcoholic fatty liver disease (NAFLD) as each is predictive of disease outcomes. A liver biopsy is the gold standard method for doing so but is impossible to perform among all patients with NAFLD. Reliable methods for noninvasively detecting for the presence of NASH and advanced fibrosis are thus a pressing need.

Gadoxetate-enhanced Abbreviated MRI for Hepatocellular Carcinoma Surveillance: Preliminary Experience.

Purpose: To describe a single-center preliminary experience with gadoxetate disodium-enhanced abbreviated MRI for hepatocellular carcinoma (HCC) screening and surveillance in patients with cirrhosis or chronic hepatitis B virus (cHBV).

Materials And Methods: This was a retrospective study of consecutive patients aged 18 years and older with cirrhosis or cHBV who underwent at least one gadoxetate-enhanced abbreviated MRI examination for HCC surveillance from 2014 through 2016. Examinations were interpreted prospectively by one of six abdominal radiologists for clinical care.

Cardiovascular Risk Categories in Patients With Nonalcoholic Fatty Liver Disease and the Role of Low-Density Lipoprotein Cholesterol.

Cardiovascular disease (CVD) is the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). The current analysis expands the knowledge on atherogenic lipid profiles in NAFLD by modeling changes in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) in a prospectively enrolling real-life study cohort to inform physicians on the cardiovascular (CV) event risk based on these changes. A total of 304 patients with histologically confirmed NAFLD were included (mean age, 52 years; equal sex distribution).

Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled phase IIb study.

Background & Aims: MSDC-0602K is a novel insulin sensitizer designed to preferentially target the mitochondrial pyruvate carrier while minimizing direct binding to the transcriptional factor PPARγ. Herein, we aimed to assess the efficacy and safety of MSDC-0602K in patients with non-alcoholic steatohepatitis.

Methods: Patients with biopsy-confirmed NASH and fibrosis (F1-F3) were randomized to daily oral placebo, or 1 of 3 MSDC-0602K doses in a 52-week double-blind study.

Effect of PNPLA3 polymorphism on diagnostic performance of various noninvasive markers for diagnosing and staging nonalcoholic fatty liver disease.

Background And Aim: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) genotype influences clinical/biochemical characteristics in patients with nonalcoholic fatty liver disease (NAFLD), but whether PNPLA3-I148M (rs738409) genotype also influences the diagnostic performance of noninvasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of noninvasive diagnostic tests for NAFLD according to PNPLA3-I148M (rs738409) genotype.

Methods: Fifty-eight healthy controls and 349 patients with biopsy-proven NAFLD were included.

Individualized risk prediction of significant fibrosis in non-alcoholic fatty liver disease using a novel nomogram.

Background: Fibrosis is deemed to be a pivotal determinant of the long-term prognosis in non-alcoholic fatty liver disease (NAFLD).

Objective: We aimed to develop a novel nomogram-based non-invasive model to accurately predict significant fibrosis in patients with NAFLD.

Methods: We designed a prospective cohort study including 207 patients with biopsy-proven NAFLD.

Homeostatic model assessment of insulin resistance closely related to lobular inflammation in nonalcoholic fatty liver disease.

Objective: Insulin resistance (IR) has been established as a major risk factor for nonalcoholic fatty liver disease (NAFLD) where it exerts effects on plasma glucose homeostasis, cellular anabolism, and organ glucose uptake. Owing to paucity of studies focused on peripheral IR in relation to pathological outcome, we aim to investigate homeostatic model assessment of insulin resistance (HOMA-IR) by histological characteristics of NAFLD.

Methods: Liver biopsy of 588 patients was screened.

Clinical Utility of an Increase in Magnetic Resonance Elastography in Predicting Fibrosis Progression in Nonalcoholic Fatty Liver Disease.

Background And Aims: Cross-sectional studies have shown that magnetic resonance elastography (MRE) is accurate in the noninvasive detection of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD). However, there are limited data on the longitudinal association between an increase in liver stiffness on MRE and fibrosis progression in NAFLD. Therefore, using a well-characterized prospective cohort of patients with biopsy-proven NAFLD, we aimed to examine the longitudinal association between a 15% increase in liver stiffness on MRE and fibrosis progression in NAFLD.

Fatty Liver Disease Caused by High-Alcohol-Producing Klebsiella pneumoniae.

The underlying etiology of nonalcoholic fatty liver disease (NAFLD) is believed to be quite varied. Changes in the gut microbiota have been investigated and are believed to contribute to at least some cases of the disease, though a causal relationship remains unclear. Here, we show that high-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) is associated with up to 60% of individuals with NAFLD in a Chinese cohort.

The Correlation between Serum Zinc Level and Liver Histology in Non-Alcoholic Steatohepatitis.

Background & Objective: The aim of this present study was to assess the relationship between serum zinc levels and liver histopathological findings in non-alcoholic steatohepatitis (NASH) patients.

Methods: This case-control study was performed in consecutively selected NASH patients who had been referred to a general hospital. The control group consisted of age and sex-matched individuals with normal physical examinations, laboratory findings, and liver ultrasounds.

PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels.

Background & Aims: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism is associated with NAFLD severity and the PNPLA3 gene is expressed in the kidneys, but whether PNPLA3 rs738409 polymorphism is also associated with renal tubular injury (RTI) is uncertain. We assessed the effect of PNPLA3 genotypes on biomarkers of RTI and glomerular function in subjects with NAFLD who had either normal (nALT) or abnormal (abnALT) alanine aminotransaminase levels.

Methods: Two hundred and seventeen patients with histologically proven NAFLD of which 75 had persistently nALT (below upper limit of normal for 3 months) were included.

Metabolic Acidosis in Critically Ill Cirrhotic Patients with Acute Kidney Injury.

The metabolic acid-base disorders have a high incidence of acute kidney injury (AKI) in critically ill cirrhotic patients (CICPs). The aims of our study were to ascertain the composition of metabolic acidosis of CICPs with AKI and explore its relationship with hospital mortality. Three-hundred and eighty consecutive CICPs with AKI were eligible for the cohort study.

Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven non-alcoholic fatty liver disease.

Background & Aims: We undertook a cross-sectional study of children/adolescents with and without non-alcoholic fatty liver disease (NAFLD) to compare the prevalence of prediabetes and diabetes, and to examine the role of abnormal glucose tolerance as a predictor of liver disease severity.

Methods: We recruited a cohort of 599 Caucasian children/adolescents with biopsy-proven NAFLD, and 118 children/adolescents without NAFLD, who were selected to be similar for age, sex, body mass index and waist circumference to those with NAFLD. The diagnosis of prediabetes and diabetes was based on either hemoglobin A1c, fasting plasma glucose or 2 h post-load glucose concentrations.

A Novel Use of Model for End-Stage Liver Disease (MELD) Score in Guiding Therapeutic Antibiotics Choice for Critically Ill Cirrhotic Patients.

BACKGROUND Inappropriate use of antibiotics results in antimicrobial resistance and dysbacteriosis. Among critically ill cirrhotic patients, consensus regarding the most optimal prescription strategy for antibiotics use has not been achieved. For these patients, the score for end-stage liver disease (MELD) demonstrated its value in predicting prognosis of cirrhosis.