Fibrosis Stage Is the Strongest Predictor for Disease-Specific Mortality in NAFLD After Up to 33 Years of Follow-Up

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e., fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (+/- 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. NAFLD patients had an increased mortality compared with the reference population (hazard ratio [HR] 1.29, confidence interval [CI] 1.04-1.59, P=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, P=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, P=0.001), infectious disease (HR 2.71, CI 1.02-7.26, P=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, P=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, P=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, P<0.001). Conclusion: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality. (Hepatology 2015;61:1547-1554)