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Gene-Environmental Interactions as Metabolic Drivers of Nonalcoholic Steatohepatitis.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide in the past few decades as a consequence of the global obesity epidemic and is associated with significant morbidity and mortality. NAFLD is closely associated with components of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease, suggesting a plausible metabolic mechanistic basis. Metabolic inflexibility is considered a nidus for NAFLD pathogenesis, causing lipotoxicity, mitochondrial dysfunction and cellular stress leading to inflammation, apoptosis and fibrogenesis, thus mediating disease progression into nonalcoholic steatohepatitis (NASH) and ultimately cirrhosis. In this review, we describe they key metabolic drivers that contribute to development of NAFLD and NASH, and we explain how NASH is a metabolic disease. Understanding the metabolic basis of NASH is crucial for the prevention and treatment of this disease.

SUBMITTER: Albhaisi S

PROVIDER: S-EPMC8142267 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Gene-Environmental Interactions as Metabolic Drivers of Nonalcoholic Steatohepatitis.

Albhaisi Somaya S Sanyal Arun J AJ

Frontiers in endocrinology 20210510

Nonalcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide in the past few decades as a consequence of the global obesity epidemic and is associated with significant morbidity and mortality. NAFLD is closely associated with components of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease, suggesting a plausible metabolic mechanistic basis. Metabolic inflexibility is considered a nidus for NAFLD pathogenesis, causing lipotox ...[more]

PMID: 34040583

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Project description:Background & aimsObese patients with nonalcoholic steatohepatitis (NASH) are at risk for cirrhosis if significant weight loss is not achieved. The single fluid-filled intragastric balloon (IGB) induces meaningful weight loss and might be used in NASH treatment. We performed an open-label prospective study to evaluate the effects of IGB placement on metabolic and histologic features of NASH.MethodsTwenty-one patients with early hepatic fibrosis (81% female; mean age, 54 years; average body mass index, 44 kg/m2) underwent magnetic resonance elastography (MRE) and endoscopic ultrasound with core liver biopsy collection at time IGB placement and removal at a single center from October 2016 through March 2018. The primary outcome measure was the changes in liver histology parameters after IGB, including change in nonalcoholic fatty liver disease activity score (NAS) and fibrosis score. We also evaluated changes in weight, body mass index, waist to hip ratio, aminotransaminases, fasting levels of lipids, fasting glucose, glycosylated hemoglobin, and MRE-detected liver stiffness.ResultsSix months after IGB, patients' mean total body weight loss was 11.7% ± 7.7%, with significant reductions in HbA1c (1.3% ± 0.5%) (P = .02). Waist circumference decreased by 14.4 ± 2.2 cm (P = .001). NAS improved in 18 of 20 patients (90%), with a median decrease of 3 points (range, 1-4 points); 16 of 20 patients (80%) had improvements of 2 points or more. Fibrosis improved by 1.17 stages in 15% of patients, and MRE-detected fibrosis improved by 1.5 stages in 10 of 20 patients (50%). Half of patients reached endpoints approved by the Food and Drug Administration of for NASH resolution and fibrosis improvement. Percent total body weight loss did not correlate with reductions in NAS or fibrosis. Other than post-procedural pain (in 5% of patients), no serious adverse events were reported.ConclusionIn a prospective study, IGB facilitated significant metabolic and histologic improvements in NASH. IGB appears to be safe and effective for NASH management when combined with a prescribed diet and exercise program. ClinicalTrials.gov no: NCT02880189.

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Gene-Environmental Interactions as Metabolic Drivers of Nonalcoholic Steatohepatitis.

Publications

Gene-Environmental Interactions as Metabolic Drivers of Nonalcoholic Steatohepatitis.

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