Interaction between alcohol consumption and metabolic syndrome in predicting severe liver disease in the general population

The metabolic syndrome and alcohol risk use are both associated with a high prevalence of hepatic steatosis, but only a minority develop liver failure or liver cancer. Few general population studies have analyzed metabolic predictors of such severe liver complications. We studied which metabolic factors best predict severe liver complications, stratified by alcohol consumption, in 6732 individuals without baseline liver disease who participated in the Finnish population-based Health 2000 Study (2000-2001), a nationally representative cohort. Follow-up data from national registers until 2013 were analyzed for liver-related admissions, mortality, and liver cancer. Baseline alcohol use and metabolic factors were analyzed by backward stepwise Cox regression analysis. Eighty-four subjects experienced a severe liver event during follow-up. In the final multivariate model, factors predictive of liver events were age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.004-1.04), sex (women: HR, 0.55; 95% CI, 0.34-0.91), alcohol use (HR, 1.002; 95% CI, 1.001-1.002), diabetes (HR, 2.73; 95% CI, 1.55-4.81), low-density lipoprotein (LDL) cholesterol (HR, 0.74; 95% CI, 0.58-0.93), and homeostasis model assessment of insulin resistance (HOMA-IR) (HR, 1.01; 95% CI, 1.004-1.02). Among alcohol risk users (210g/week for men,140g/week for women), diabetes (HR, 6.79; 95% CI, 3.18-14.5) was the only significant predictor. Among nonrisk drinkers, age, alcohol use, smoking, waist circumference, low LDL cholesterol and HOMA-IR were significant independent predictors. The total-to-LDL cholesterol ratio and waist circumference-to-body mass index ratio emerged as additional independent predictors. Conclusion: Multiple components of the metabolic syndrome independently affected the risk for severe liver disease. Alcohol was significant even when average alcohol consumption was within the limits currently defining nonalcoholic fatty liver disease. (Hepatology 2018;67:2141-2149)