Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes

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Abstract

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. Global prevalence of NAFLD is 25.24% (95% CI: 22.10-28.65) with highest prevalence in the Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38-61.20), type 2 diabetes (22.51%; 95% CI: 17.92-27.89), hyperlipidemia (69.16%; 95% CI: 49.91-83.46%), hypertension (39.34%; 95% CI: 33.15-45.88), and metabolic syndrome (42.54%; 95% CI: 30.06-56.05). 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).

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Most cited references 11

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Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults.

Min Huang, S Yueh, Chun-Song Yang … (2006)

The prevalence of nonalcoholic fatty liver disease (NAFLD) is rarely reported in Taiwan. To determine the prevalence and risk factors of NAFLD in an adult population of Taiwan. The cross-sectional community study examined 3245 adults in a rural village of Taiwan. The diagnostic criteria for NAFLD included no excessive alcohol intake, no chronic viral hepatitis, no known etiologies of liver disease, and ultrasonography consistent with fatty liver. The prevalence of NAFLD was 11.5% (372/3245). The risk factors for NAFLD in the general population were male sex [odds ratio (OR), 1.44; 95% confidence interval (CI), 1.09-1.90], elevated alanine aminotransferase (ALT) (OR, 5.66; 95% CI, 3.99-8.01), obesity (OR, 7.21; 95% CI, 5.29-9.84), fasting plasma glucose > or =126 mg/dL (OR, 2.08; 95% CI, 1.41-3.05), total cholesterol > or =240 mg/dL (OR, 1.50; 95% CI, 1.06-2.13), triglyceride > or =150 mg/dL (OR, 1.76; 95% CI, 1.32-2.35), and hyperuricemia (OR, 1.53; 95% CI, 1.16-2.01). Age > or =65 years was inversely related to NAFLD (OR, 0.53; 95% CI, 0.36-0.77). The only NAFLD risk factors among nonobese subjects were age between 40 and 64 years (OR, 2.35; 95% CI, 1.34-4.11, P=0.003), elevated ALT (OR, 15.45; 95% CI, 8.21-29.09, P or =150 mg/dL (OR, 2.48; 95% CI, 1.42-4.32, P=0.001). In subjects with NAFLD, the prevalence of elevated ALT in the presence of each metabolic risk factor, such as obesity, fasting plasma glucose > or =126 mg/dL, total cholesterol > or =240 mg/dL, triglyceride > or =150 mg/dL, and hyperuricemia, did not differ from that of subjects with normal ALT levels. NAFLD is closely associated with elevated ALT, obesity, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. Among the metabolic disorders, only hypertriglyceridemia was related to NAFLD in nonobese subjects. Serum ALT level was not a good predictor of metabolic significance in subjects with NAFLD.

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Cohort study of non-alcoholic fatty liver disease, NAFLD fibrosis score, and the risk of incident diabetes in a Korean population.

Juhee Cho, Woo-Suk Jung, K Yun … (2013)

No study has evaluated an association between non-alcoholic fatty liver disease (NAFLD) severity and the incidence of diabetes. We examined whether NAFLD and its severity-using the NAFLD fibrosis score (NFS)-predict the development of diabetes. A cross-sectional study was performed in 43,166 apparently healthy Koreans aged 30-59 years, who underwent a health checkup in 2005 and 2006. Of these, 38,291 subjects without diabetes were followed annually or biennially until December 2011 for the cohort study. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or other identifiable causes. The NFS was used to categorize the severity of fibrosis. Diabetes was defined as fasting serum glucose ≥126 mg/dl, glycated hemoglobin (HbA1c) ≥6.5%, or medication use for diabetes. During 175,996 person-years of follow-up, 2,025 participants developed diabetes. An increase across NAFLD categories was positively associated with an increased risk of diabetes in both the cross-sectional and cohort studies in a dose-response manner (P-trend <0.001). In multivariate-adjusted models, the hazard ratios (95% confidence intervals) for diabetes comparing NAFLD with low NFS and NAFLD with intermediate or high NFS vs. no NAFLD were 2.00 (1.79-2.24) and 4.74 (3.67-6.13), respectively. This association remained significant even in subjects with fasting glucose <100 mg/dl and subjects with HbA1c <5.8%. In this cohort study of a healthy Korean population, NAFLD and its severity using NFS were independently and strongly associated with increased incidence of diabetes in men and women-even with a euglycemic range of glucose and HbA1c.

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Independent Association Between Improvement of Nonalcoholic Fatty Liver Disease and Reduced Incidence of Type 2 Diabetes.

Hajime Yamazaki, Toru Tsuboya, Kunihiko Tsuji … (2015)

Only a few studies have evaluated the long-term effects of nonalcoholic fatty liver disease (NAFLD) on type 2 diabetes mellitus (T2DM), and none have examined whether NAFLD improvement reduces T2DM incidence. We investigated the association between NAFLD improvement and T2DM incidence.