Genetic and lifestyle risk factors for advanced liver disease among men and women.

Abstract

Liver disease is traditionally categorized as alcoholic and non-alcoholic. We studied various risk factors predictive of advanced non-viral liver disease in general population and analyzed the interaction between these factors and alcohol consumption. Persons without underlying liver disease who participated in the Health2000 or FINRISK studies 1992-2012 comprised a cohort of 41260 individuals. Pattern of alcohol consumption and metabolic, lifestyle-related, and anthropometric parameters were analyzed with Cox regression analysis using severe liver disease hospitalization, cancer, or death as end-point. Viral liver diseases were excluded. A total of 355 liver events occurred during the mean 12.4-year follow-up (511789 person-years). In the multivariate model, age (hazard ratio [HR] 1.03, P=0.0083 for men; HR 1.04, P=0.0198 for women), waist-to-hip ratio (WHR) (HR 1.52, P=0.0006 for men; HR 1.58, P=0.0167 for women), patatin-like phospholipase-containing domain 3 mutations (HR 1.9, P=0.024 for men; HR 2.7, P=0.0109 for women), and weekly binge drinking (HR 2.4, P=0.0024 for men; HR 7.4, P<0.0001 for women) predicted development of severe liver disease. Among men, diabetes (HR 2.7, P=0.0002), average alcohol consumption (HR for 10g/day 1.1, P=0.0022), non-married status (HR 1.9, P=0.0397 for single; HR 2.4, P=0.0002 for widowed/separated), and serum high-density lipoprotein (HR 2.2, P=0.0022) and non-high-density lipoprotein cholesterol (HR 1.2, P=0.0237) were additional risk factors. Alcohol intake increased the risk especially among persons with high WHR (P for interaction 0.009). Age, patatin-like phospholipase-containing domain 3 haplotype, and WHR increase the risk for development of severe liver disease. We found strong synergism between alcohol and central obesity. Binge drinking is an additional risk factor.