Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of hepatocellular carcinoma (HCC), cirrhosis, overall mortality, and liver-related mortality were determined. NASH required histological diagnosis. All studies were reviewed by three independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication, and study population. We used random-effects models to provide point estimates (95% confidence interval [CI]) of prevalence, incidence, mortality and incidence rate ratios, and metaregression with subgroup analysis to account for heterogeneity. Of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. . Fibrosis progression proportion, and mean annual rate of progression in NASH were 40.76% (95% CI: 34.69-47.13) and 0.09 (95% CI: 0.06-0.12). HCC incidence among NAFLD patients was 0.44 per 1,000 person-years (range, 0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77 per 1,000 (range, 0.33-1.77) and 11.77 per 1,000 person-years (range, 7.10-19.53) and 15.44 per 1,000 (range, 11.72-20.34) and 25.56 per 1,000 person-years (range, 6.29-103.80). Incidence risk ratios for liver-specific and overall mortality for NAFLD were 1.94 (range, 1.28-2.92) and 1.05 (range, 0.70-1.56). Conclusions: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous. (HEPATOLOGY 2016;64:73-84)

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The analysis quantifies the enormity of the clinical and economic burdens of NAFLD, which will likely increase as the incidence of NAFLD continues to rise. (Hepatology 2016;64:1577-1586).

Hepatocellular carcinoma (HCC) is increasingly reported in patients with nonalcoholic fatty liver disease (NAFLD). Our aim was to assess the prevalence and mortality of patients with NAFLD-HCC. We examined Surveillance, Epidemiology and End Results (SEER) registries (2004)(2005)(2006)(2007)(2008)(2009)) with Medicare-linkage files for HCC, which was identified by the International Classification of Diseases for Oncology, third edition codes using topography and morphology codes 8170-8175. Medicare-linked data was used to identify NAFLD, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease (ALD), and other liver disease using International Classification of Diseases, Ninth Revision, Clinical Modification codes. NAFLD was also defined by clinical diagnosis (cryptogenic cirrhosis, obese-diabetics with cryptogenic liver disease). A logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HCC. In addition, adjusted hazard ratios for 1-year mortality were estimated by Cox's proportional hazard regression. A total of 4,929 HCC cases and 14,937 controls without HCC were included. Of the HCC cases, 54.9% were related to HCV, 16.4% to ALD, 14.1% to NAFLD, and 9.5% to HBV. Across the 6-year period (2004 to 2009), the number of NAFLD-HCC showed a 9% annual increase. NAFLD-HCC were older, had shorter survival time, more heart disease, and were more likely to die from their primary liver cancer (all P < 0.0001). Of those who received a transplant after HCC (n 5 488), only 5% were related to NAFLD-HCC. In multivariate analysis, NAFLD increased the risk of 1-year mortality (OR, 1.21; 95% CI: 1.01-1.45). Additionally, older age, lower income, unstaged HCC increased risk of 1-year mortality while receiving a liver transplant (LT), and having localized tumor stage were protective (all P < 0.05). Conclusions: NAFLD is becoming a major cause of HCC in the United States. NAFLD HCC is associated with shorter survival time, more advanced tumor stage, and lower possibility of receiving a LT.

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