Metabolic and Genetic Risk Factors Are the Strongest Predictors of Severity of Alcohol-Related Liver Fibrosis.
Alcohol Drinking
/ adverse effects
Cholesterol
Cross-Sectional Studies
Fatty Liver, Alcoholic
/ genetics
Fibrosis
Genetic Predisposition to Disease
Humans
Insulin Resistance
Lipase
/ genetics
Liver
/ pathology
Liver Cirrhosis
/ genetics
Membrane Proteins
/ genetics
Middle Aged
Polymorphism, Single Nucleotide
Risk Factors
Triglycerides
Alcoholic Liver Disease
Fatty Liver
Genetics
Insulin Resistance
Journal
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
08
09
2020
revised:
03
11
2020
accepted:
25
11
2020
pubmed:
7
12
2020
medline:
28
7
2022
entrez:
6
12
2020
Statut:
ppublish
Résumé
Individual risk for developing alcohol-related liver disease (ALD) varies greatly. We hypothesized that metabolic risk factors and genetic polymorphisms predict severity of ALD. Biopsy-controlled, cross-sectional study in patients with a history of excessive drinking. We measured the homeostatic model assessment of insulin resistance (HOMA-IR), plasma triglycerides, high- and low-density lipoproteins (HDL, LDL), and total cholesterol. Moreover, we genotyped four single nucleotide polymorphisms in PNPLA3 (rs738409C>G), TM6SF2 (rs58542926C>T), MBOAT7 (rs641738C>T), and HSD17B13 (rs72613567T>TA). We assessed predictors of higher fibrosis stage using multivariable ordered logistic regression. Of 325 included patients, 25% had severe fibrosis or cirrhosis and 59% had HOMA-IR ≥2.5. HOMA-IR increased for each fibrosis stage, while there was a similar decrease in LDL and total cholesterol. Individuals with risk variant PNPLA3 rs738409-G or TM6SF2 rs58542926-T had higher fibrosis stage. In multivariable regression, HOMA-IR ≥2.5 (OR = 3.04, 95% CI 1.90-4.87), LDL <2.60 mmol/L (OR = 2.05, 95% CI 1.33-3.16), TM6SF2 rs58542926-T (OR = 1.99, 95% CI 1.17-3.37), age above 50 years (OR = 1.66, 95% CI 1.03-2.70), and PNPLA3 rs738409-G (OR = 1.54, 95% CI 1.11-2.12) independently predicted higher fibrosis stage. Independent predictors of hepatic inflammatory activity were HOMA-IR, active drinking, age, and PNPLA3 risk variant. Active drinking, elevated triglycerides, and PNPLA3 risk variant predicted steatosis. Insulin resistance is the strongest predictor of liver fibrosis stage and hepatic inflammation in patients with alcohol-related liver disease. Genetic susceptibility further aggravates this risk. These data highlight the clinical value of detailed metabolic and genetic profiling of patients with excessive alcohol use.
Sections du résumé
BACKGROUND & AIMS
Individual risk for developing alcohol-related liver disease (ALD) varies greatly. We hypothesized that metabolic risk factors and genetic polymorphisms predict severity of ALD.
METHODS
Biopsy-controlled, cross-sectional study in patients with a history of excessive drinking. We measured the homeostatic model assessment of insulin resistance (HOMA-IR), plasma triglycerides, high- and low-density lipoproteins (HDL, LDL), and total cholesterol. Moreover, we genotyped four single nucleotide polymorphisms in PNPLA3 (rs738409C>G), TM6SF2 (rs58542926C>T), MBOAT7 (rs641738C>T), and HSD17B13 (rs72613567T>TA). We assessed predictors of higher fibrosis stage using multivariable ordered logistic regression.
RESULTS
Of 325 included patients, 25% had severe fibrosis or cirrhosis and 59% had HOMA-IR ≥2.5. HOMA-IR increased for each fibrosis stage, while there was a similar decrease in LDL and total cholesterol. Individuals with risk variant PNPLA3 rs738409-G or TM6SF2 rs58542926-T had higher fibrosis stage. In multivariable regression, HOMA-IR ≥2.5 (OR = 3.04, 95% CI 1.90-4.87), LDL <2.60 mmol/L (OR = 2.05, 95% CI 1.33-3.16), TM6SF2 rs58542926-T (OR = 1.99, 95% CI 1.17-3.37), age above 50 years (OR = 1.66, 95% CI 1.03-2.70), and PNPLA3 rs738409-G (OR = 1.54, 95% CI 1.11-2.12) independently predicted higher fibrosis stage. Independent predictors of hepatic inflammatory activity were HOMA-IR, active drinking, age, and PNPLA3 risk variant. Active drinking, elevated triglycerides, and PNPLA3 risk variant predicted steatosis.
CONCLUSIONS
Insulin resistance is the strongest predictor of liver fibrosis stage and hepatic inflammation in patients with alcohol-related liver disease. Genetic susceptibility further aggravates this risk. These data highlight the clinical value of detailed metabolic and genetic profiling of patients with excessive alcohol use.
Identifiants
pubmed: 33279778
pii: S1542-3565(20)31628-1
doi: 10.1016/j.cgh.2020.11.038
pii:
doi:
Substances chimiques
Membrane Proteins
0
Triglycerides
0
Cholesterol
97C5T2UQ7J
Lipase
EC 3.1.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1784-1794.e9Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.