Objective: Case series suggest that nonalcoholic fatty liver disease (NAFLD) is associated with increased all-cause and cardiovascular mortality. The current study compared the survival of subjects with and without suspected NAFLD in a population-based cohort, and placed the finding in the context of previously published case series.

Methods: Primary analysis assessed mortality for NHANES-III participants with and without suspected NAFLD using the National Death Index. Suspected NAFLD was based upon unexplained ALT elevation. The Olmsted County and Cleveland Clinic case series were also used for comparison. Survivals were compared using Proportional Hazards Model and direct age standardization.

Results: The NHANES cohort included 980 with and 6,594 subjects without suspected NAFLD. Over a mean of 8.7 yr, suspected NAFLD had a hazards ratio of 1.37 (95% CI 0.98-1.91) for all-cause mortality. In the 45-54 age group, suspected NAFLD had significantly higher all-cause (4.40 95% CI 1.27-13.23) and cardiovascular mortality (8.15, 95% CI 2.00-33.20) after adjusting for conventional cardiovascular risk factors. The age-standardized rate per 10,000 per year was 129 (95% CI 118-140) for the NHANES non-NAFLD cohort, 154 (95% CI 116-198) for the NHANES suspected NAFLD cohort, 214 (95% CI 157-279) for the Olmsted County series, and 426 (95% CI 298-573) for the Cleveland Clinic series.

Conclusion: The magnitude of mortality risk in NAFLD depends on the setting and method of ascertainment. Suspected NAFLD in the 45-54 age group is a strong independent risk factor for cardiovascular death and warrants further cardiovascular risk management guidelines.