The associations between modifiable risk factors and nonalcoholic fatty liver disease: A comprehensive Mendelian randomization study

Hepatology, Journal Year: 2022, Volume and Issue: 77(3), P. 949 - 964

Published: Aug. 16, 2022

Background and Aims: Early identification of modifiable risk factors is essential for the prevention nonalcoholic fatty liver disease (NAFLD). We aimed to systematically explore relationships between genetically predicted NAFLD. Approach Results: applied univariable multivariable Mendelian randomization analyses 35 also evaluated combined results in three independent large genome‐wide association studies. Genetically alcohol frequency, elevated serum levels enzymes, triglycerides, C‐reactive protein, obesity traits, including body mass index, waist circumference, fat mass, were associated with increased risks NAFLD (all p < 0.05). Poor physical condition had a suggestive (odds ratio [OR] = 2.63, 0.042). instrumented type 2 diabetes (T2DM), hypothyroidism, hypertension all NAFLD, ORs (95% confidence interval) 1.508 (1.20–1.90), 13.08 (1.53–111.65), 3.11 (1.33–7.31) 1‐U increase log‐transformed odds, respectively. The positive associations T2DM remained significant analyses. from discovery two replication datasets further confirmed that poor condition, T2DM, significantly whereas higher education high‐density lipoprotein cholesterol (HDL‐cholesterol) could lower risk. Conclusions: an HDL‐cholesterol decreased

Language: Английский

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Links between metabolic syndrome and metabolic dysfunction-associated fatty liver disease

Trends in Endocrinology and Metabolism, Journal Year: 2021, Volume and Issue: 32(7), P. 500 - 514

Published: May 8, 2021

Language: Английский

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Management of non-alcoholic fatty liver disease

BMJ, Journal Year: 2021, Volume and Issue: unknown, P. m4747 - m4747

Published: Jan. 18, 2021

ABSTRACT Non-alcoholic fatty liver disease is a very common medical condition, driven by combination of genetic and lifestyle factors, ultimately producing severe chronic increased cardiovascular risk. Most people are asymptomatic for long time, their daily life unaffected, leading to difficulty in identifying managing who slowly progress non-alcoholic steatohepatitis (NASH), NASH-cirrhosis, eventually hepatocellular carcinoma. Despite advances the understanding pathogenic mechanisms identification fibrosis as strongest factor predicting progression, no specific treatments have been approved regulatory agencies. Outside controlled trials, treatment generally limited intervention aimed at weight loss. Pioglitazone remains drug choice reduce progression with diabetes, although it often used off-label absence diabetes. Vitamin E mainly children may be considered adults without Several drugs under investigation according agreed targets reduced NASH activity worsening or improving NASH. Anti-inflammatory, anti-fibrotic agents metabolism modulators tested either phase III IIb randomized trials; few failed, others produced marginally positive results, but only being extension studies. The development non-invasive, easily repeatable surrogate biomarkers and/or imaging tools crucial facilitate clinical studies limit biopsy.

Language: Английский

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Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator‐activated receptor α modulator (SPPARMα), versus placebo in patients with non‐alcoholic fatty liver disease

Alimentary Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 54(10), P. 1263 - 1277

Published: Sept. 16, 2021

Summary Background Pemafibrate is a novel, selective peroxisome proliferator‐activated receptor α modulator (SPPARMα). In mice, improved the histological features of non‐alcoholic steatohepatitis (NASH). patients with dyslipidaemia, it serum alanine aminotransferase (ALT). Aims To evaluate efficacy and safety in high‐risk, fatty liver disease (NAFLD). Methods This double‐blind, placebo‐controlled, randomised multicentre, phase 2 trial 118 (1:1) to either 0.2 mg or placebo, orally, twice daily for 72 weeks. The key inclusion criteria included fat content ≥10% by magnetic resonance imaging‐estimated proton density fraction (MRI‐PDFF); stiffness ≥2.5 kPa, elastography (MRE); elevated ALT levels. primary endpoint was percentage change MRI‐PDFF from baseline week 24. secondary endpoints MRE‐based stiffness, ALT, fibrosis markers lipid parameters. Results There no significant difference between groups (−5.3% vs −4.2%; treatment −1.0%, P = 0.85). However, significantly decreased compared placebo at 48 (treatment −5.7%, 0.036), maintained −6.2%, 0.024), reduction LDL‐C. Adverse events were comparable therapy well tolerated. Conclusions did not decrease but had stiffness. may be promising therapeutic agent NAFLD/NASH, also candidate combination agents that reduce content. ClinicalTrials.gov, number: NCT03350165.

Language: Английский

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The role of hepatokines in NAFLD

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(2), P. 236 - 252

Published: Feb. 1, 2023

Language: Английский

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