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)

The long-term survival of subjects with nonalcoholic fatty liver disease (NAFLD) in comparison with both individuals with elevated transaminases attributable to other causes and the general poulation is poorly characterized. This study was undertaken to determine the frequency of NAFLD in a cohort of subjects who underwent liver biopsy from 1980 to 1984 because of elevated liver enzymes, and to assess mortality among subjects with NAFLD in comparison with the general Swedish population. The 256 subjects (61% men) had a mean age of 45 ± 12 years at the inclusion. Liver biopsies were blindly scored for NAFLD and nonalcoholic steatohepatitis (NASH). Causes of death were ascertained from the national Swedish Cause of Death Registry. Fatty liver was detected in 143 of the 256 subjects, including 25 (10%) with alcoholic fatty liver disease and 118 (46%) exhibiting NAFLD. Of those, 51 (20%) were classified as NASH and 67 (26%) as nonalcoholic bland steatosis. Cirrhosis was present in 9% at inclusion. During the follow-up period, 113 (44%) of the total population and 47 (40%) of the 118 subjects diagnosed with NAFLD died. Of the 113 deaths, 37 were of cardiovascular disease and 16 of liver diseases. Compared with the total Swedish population, adjusted for sex, age, and calendar period, subjects with NAFLD exhibited a 69% increased mortality (standardized mortality ratio [SMR] = 1.69; 95% confidence interval [CI], 1.24–2.25); subjects with bland steatosis, a 55% increase (SMR, 1.55; 95% CI, 0.98–2.32; P = 0.062); and subjects with NASH, 86% (SMR, 1.86; 95% CI, 1.19–2.76; P = 0.007). Conclusion: Patients with NASH are at increased risk of death compared with the general population. Liver disease is the third most common cause of death among patients with NAFLD. (Hepatology 2009.)

Background. The long-term effect of sustained virologic response (SVR) to antiviral therapy on the risk of developing hepatocellular carcinoma (HCC), liver complications, liver-related death, and overall death in hepatitis C virus (HCV)–infected patients with liver cirrhosis is not fully known. Methods. These risks were evaluated during long-term follow-up in 351 patients with HCV-related cirrhosis. One hundred ten patients with SVR, 193 with non-SVR, and 48 who were untreated were included in a multicenter cohort that was initiated in 2001 and prospectively followed up for a mean of 5.3 (SD, 2.8) years. Complementary follow-up data from national registries were used to minimize the loss of patients during follow-up. Results. Six patients with SVR developed HCC at 0.04, 0.64, 2.4, 7.4, 7.4, and 7.6 years, respectively, after achieving SVR. The incidences of HCC, any liver complication, liver-related death, and overall death per 100 person-years were significantly lower in SVR time with 1.0, 0.9, 0.7, and 1.9, compared to 2.3, 3.2, 3.0, and 4.1 in non-SVR and 4.0, 4.9, 4.5, and 5.1 in untreated time. The long-term consequences did not decline significantly after >3 years versus during the first 3 years of follow-up. Conclusions. The risk for HCC, liver decompensation, and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR, but a long-term risk of developing HCC remains for up to 8 years. Cirrhotic patients with HCV who achieve SVR should therefore maintain long-term surveillance for HCC. Future studies aimed to better identify those with remaining long-term risk for HCC are needed.