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.

Epidemiology of non-alcoholic fatty liver disease and hepatocellular carcinoma

“…However, in patients with NAFLD, metabolic disorders such as type 2 diabetes or insulin resistance affect the risk of HCC, regardless of the presence of cirrhosis. [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] ( Fig. 1 ) The pathway to carcinogenesis might involve the release of inflammatory cytokines, such as tumour necrosis factor-α (TNF), interleukin 6 (IL6), leptin, and resistin, along with decreased amounts of adiponectin.…”

“…As noted previously, HCC can develop in patients with NAFLD who do not have cirrhosis. 36 , 37 , 72 , 80 , 81 , [87] , [88] , [89] , [90] Since most HCC guidelines recommend surveillance for patients with cirrhosis, diagnosing HCC before symptoms develop is difficult. 43 , 89 On the other hand, recommending universal screening for all patients with NAFLD is not currently cost effective.…”

“…For example, patients with NAFLD with multiple risk factors (older obese men with diabetes and hypertension) might be considered for a targeted surveillance programme. 36 , 37 , 72 , 80 , 81 , [86] , [87] , [88] , [89] , [90] , [91] , [92] Large, prospective studies are needed to identify risk factors and develop appropriate surveillance protocols. Non-invasive tests are also needed to identify patients at high risk of HCC, as patients with NAFLD and evidence of advanced fibrosis might also be considered for HCC screening.…”

“…(37)(38)73,(81)(82)(87)(88)(89)(90)(91)(92)(93) Large, prospective studies are needed to identify risk factors and develop appropriate surveillance protocols. Noninvasive tests are also needed to identify patients at high risk of HCC as patients with NAFLD J o u r n a l P r e -p r o o f and evidence of advanced fibrosis might also be a consideration for HCC screening (94)(95)(96)(97)(98)…”

Chronic liver disease: Global perspectives and future challenges to delivering quality health care

“…Wang and colleagues report that liver transplant trends in the United States reflect the emergence of NAFLD as an important cause for end-stage liver disease and hepatocellular carcinoma [ 3 ]. However, Hirose and colleagues report a 19-year follow-up study of biopsy-proven NAFLD patients in Japan where the prevalence of diabetes, hypertension, and disease prognosis were similar in lean NAFLD and obese NAFLD, suggesting that risk stratification in NAFLD should therefore not be solely based on one’s body-mass index [ 4 ]. Chen and colleagues also report that a high prevalence of advanced liver fibrosis was detected in NAFLD diabetics in Singapore, leading to the question of whether screening for NAFLD or increased liver stiffness measurements should be advocated during diabetes complication screening [ 5 ].…”