Metabolic and Genetic Risk Factors Are the Strongest Predictors of Severity of Alcohol-Related Liver Fibrosis

• DOI: 10.1016/j.cgh.2020.11.038
• Publication Date: 2020-12-04T07:04:11Z
• Authors: Mads Israelsen; Helene Bæk Juel; Sönke Detlefsen; Bjørn Stæhr Madsen; Ditlev Nytoft Ras...; Trine R. Larsen; Maria Kjærgaard; Mary Jo Fernandes...; Stefan Stender; Torben Hansen; Aleksander Krag; Maja Thiele
• Keywords: Steatosis; Homeostatic model assessment

Background & AimsIndividual risk for developing alcohol-related liver disease (ALD) varies greatly. We hypothesized that metabolic factors and genetic polymorphisms predict severity of ALD.MethodsBiopsy-controlled, cross-sectional study in patients with a history excessive drinking. measured the homeostatic model assessment insulin resistance (HOMA-IR), plasma triglycerides, high- low-density lipoproteins (HDL, LDL), total cholesterol. Moreover, we genotyped four single nucleotide PNPLA3 (rs738409C>G), TM6SF2 (rs58542926C>T), MBOAT7 (rs641738C>T), HSD17B13 (rs72613567T>TA). assessed predictors higher fibrosis stage using multivariable ordered logistic regression.ResultsOf 325 included patients, 25% had severe or cirrhosis 59% HOMA-IR ≥2.5. increased each stage, while there was similar decrease LDL Individuals variant rs738409-G rs58542926-T stage. In regression, ≥2.5 (OR = 3.04, 95% CI 1.90-4.87), <2.60 mmol/L 2.05, 1.33-3.16), 1.99, 1.17-3.37), age above 50 years 1.66, 1.03-2.70), 1.54, 1.11-2.12) independently predicted Independent hepatic inflammatory activity were HOMA-IR, active drinking, age, variant. Active elevated steatosis.ConclusionsInsulin is strongest predictor inflammation disease. Genetic susceptibility further aggravates this risk. These data highlight clinical value detailed profiling alcohol use. Individual ALD. Biopsy-controlled, regression. Of steatosis. Insulin