Gallstone Disease and Its Association With Nonalcoholic Fatty Liver Disease, All-Cause and Cause-Specific Mortality

Abstract

Background & aims: Presence of gallstone disease may influence outcomes in patients with nonalcoholic fatty liver disease (NAFLD). We studied the impact of gallstone disease on mortality in individuals with and without NAFLD.

Methods: Prospective cohort study used the Third National Health and Nutrition Examination Survey (1988-1994) with mortality data through 2015. Gallstone disease was defined as ultrasonographic evidence of gallstones or absence of the gallbladder (prior cholecystectomy). NAFLD was defined using standardized ultrasonographic criteria.

Results: Gallstone disease and cholecystectomy were independently associated with NAFLD (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.43-2.15 for gallstone disease and OR, 2.77; 95% CI, 2.01-3.83 for cholecystectomy compared with no gallstone disease). During the median follow-up of 23 years, gallstone disease was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.19; 95% CI, 1.05-1.37) and cause-specific mortality. Gallstone disease was associated with a higher risk of all-cause mortality in non-NAFLD sub-cohort (HR, 1.42; 95% CI, 1.23-1.64) but not in NAFLD (HR, 1.03; 95% CI, 0.87-1.22). Gallstone disease was associated with a higher risk of cardiovascular-related (HR, 1.40; 95% CI, 1.10-1.78) and cancer-related (HR, 1.71; 95% CI, 1.18-2.48) mortality in non-NAFLD sub-cohort. Gallstone disease was associated with increased cardiovascular mortality (HR, 1.36; 95% CI, 1.05-1.77) in NAFLD.

Conclusions: Gallstone disease is an independent risk factor for NAFLD, but gallstone disease is not associated with all-cause mortality in individuals with NAFLD. Screening for gallstone disease in individuals at risk for developing NAFLD may help with risk stratification for all-cause mortality related to gallstone disease.

Keywords: Cardiovascular; Death; Hepatic Steatosis; NHANES.