Nineteen-year prognosis in Japanese patients with biopsy-proven nonalcoholic fatty liver disease: Lean versus overweight patients

Abstract

Background: Many studies have investigated the prognosis of nonalcoholic fatty liver disease (NAFLD); however, most studies had a relatively short follow-up. To elucidate the long-term outcome of NAFLD, we conducted a retrospective cohort study of patients with biopsy-proven NAFLD.

Methods: We re-evaluated 6080 patients who underwent liver biopsy from 1975 to 2012 and identified NAFLD patients without other etiologies. With follow-up these patients, we evaluated the outcome-associated factors.

Results: A total of 223 patients were enrolled, 167 (74.9%) was non-alcoholic steatohepatitis (NASH). The median follow-up was 19.5 (0.5-41.0) years and 4248.3 person-years. The risk of type 2 diabetes mellitus (T2DM) and hypertension was 11.7 (95% confidence interval [CI] 8.70-15.6) and 7.99 (95% CI 6.09-10.5) times higher, respectively, in NAFLD patients than in the general population. Twenty-three patients died, 22 of whom had NASH. Major causes of death were extrahepatic malignancy and cardiovascular disease (21.7%) followed by liver-related mortality (13.0%). All-cause mortality was significantly higher in NASH patients than in nonalcoholic fatty liver patients (P = 0.041). In multivariate analysis, older age (hazard ratio [HR] 1.09 [95% CI 1.05-1.14], P<0.001) and T2DM (HR 2.87 [95% CI 1.12-7.04], P = 0.021) were significantly associated with all-cause mortality. The factors significantly associated with liver-related events were older age, T2DM, milder hepatic steatosis, and advanced liver fibrosis. Body mass index wasn't associated with either mortality or liver-related events.

Conclusions: T2DM was highly prevalent in NAFLD patients and was significantly associated with both all-cause mortality and liver-related events. The lean patients' prognosis wasn't necessarily better than that of overweight patients.

Fig 1. Algorithm of patient selection.

NAFLD, nonalcoholic fatty liver disease; NAFL, nonalcoholic fatty liver; NASH, nonalcoholic steatohepatitis.

Fig 2. All-cause mortality in patients with nonalcoholic fatty liver disease (NAFLD).

(A) All-cause mortality in NAFL and NASH patients. (B) All-cause mortality in lean and overweight NAFLD patients. (C) All-cause mortality in NAFLD patients with and without type 2 diabetes mellitus.

Fig 3. Cumulative occurrence rate of liver-related events.

(A) Cumulative occurrence rate of liver-related events in patients with nonalcoholic fatty liver disease (NAFLD) with and without type 2 diabetes mellitus. (B) Cumulative occurrence rate of liver-related events in NALFD patients with grade <2 steatosis and those with grade ≥2 steatosis. (C) Cumulative occurrence rate of liver-related events in NALFD patients with stage ≤2 fibrosis and in those with stage ≥3 fibrosis.