Background and Aims: NAFLD is a leading cause of liver-related morbidity and mortality. We assessed the global and regional prevalence, incidence, and mortality of NAFLD using an in-depth meta-analytic approach. Approach and Results: PubMed and Ovid MEDLINE were searched for NAFLD population-based studies from 1990 to 2019 survey year (last published 2022) per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Meta-analysis was conducted using random-effects models. Bias risk assessment was per Joanna Briggs Institute. Of 2585 studies reviewed, 92 studies (N=9,361,716) met eligibility criteria. Across the study period (1990–2019), meta-analytic pooling of NAFLD prevalence estimates and ultrasound-defined NAFLD yielded an overall global prevalence of 30.05% (95% CI: 27.88%–32.32%) and 30.69% (28.4–33.09), respectively. Global NAFLD prevalence increased by +50.4% from 25.26% (21.59–29.33) in 1990–2006 to 38.00% (33.71–42.49) in 2016–2019 (p<0.001); ultrasound-defined NAFLD prevalence increased by +38.7% from 25.16% (19.46–31.87) in 1990–2006 to 34.59% (29.05–40.57) (p=0.029). The highest NAFLD prevalence was in Latin America 44.37% (30.66%–59.00%), then Middle East and North Africa (MENA) (36.53%, 28.63%–45.22%), South Asia (33.83%, 22.91%–46.79%), South-East Asia (33.07%, 18.99%–51.03%), North America (31.20%, 25.86%–37.08%), East Asia (29.71%, 25.96%–33.76%), Asia Pacific 28.02% (24.69%–31.60%), Western Europe 25.10% (20.55%–30.28%). Among the NAFLD cohort diagnosed without a liver biopsy, pooled mortality rate per 1000 PY was 12.60 (6.68–23.67) for all-cause mortality; 4.20 (1.34–7.05) for cardiac-specific mortality; 2.83 (0.78–4.88) for extrahepatic cancer-specific mortality; and 0.92 (0.00–2.21) for liver-specific mortality. Conclusions: NAFLD global prevalence is 30% and increasing which requires urgent and comprehensive strategies to raise awareness and address all aspects of NAFLD on local, regional, and global levels.

Although nonalcoholic fatty liver disease (NAFLD) is associated with obesity, it can also occur in lean and metabolically normal individuals. Our aim was to determine the effect of different combinations of abdominal adiposity and overall adiposity on the mortality of NAFLD. The Third National Health and Nutrition Examination Survey with mortality data from the National Death Index were used. NAFLD was defined as steatosis without other liver diseases. Body composition was categorized according to waist circumference (WC) and body mass index (BMI). Obesity pattern was defined according to BMI (lean, overweight, and obese) and WC (normal and obese) using accepted definitions. The “metabolically abnormal” group had visceral obesity, insulin resistance, type 2 diabetes, hypertension, or hyperlipidemia. Of the 9,341 study individuals (47.9% male; 76.8% white), NAFLD was present in 3,140 (33.6%), of whom 0.6% had lean BMI and normal WC, and 1.7% had lean BMI and obese WC. The prevalence of metabolically normal NAFLD was 3.26% (95% confidence interval [CI]: 2.62%‐3.90%), with most of these subjects having lean BMI (79.2%). During an average follow‐up of 22.4 years, 24.1% of the subjects died from all causes. Among these deceased individuals, 41.7% had NAFLD at baseline. Causes of death were cardiovascular disease (24.8%), cancer‐related (24.3%), type 2 diabetes–related (4.4%), and liver‐related (1.7%). Individuals with NAFLD who were lean by BMI but obese by WC had higher risk of all‐cause mortality. Individuals with NAFLD with normal BMI but obese WC had a higher risk of cardiovascular mortality (hazard ratio 2.63 [95% CI: 1.15‐6.01]) as compared with overweight (by BMI) NAFLD with normal WC. Conclusion: The risk of mortality in NAFLD can be affected by the presence of visceral obesity, especially in the lean BMI group. These data have important management implications for patients with NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease worldwide. This is primarily driven by the global epidemic of obesity and diabetes as well as the aging of the general population. Most of the epidemiology data of NAFLD for North America are published from studies originating in the United States (U.S.). The overall prevalence of NAFLD in the U.S. is estimated to be 24%. Hispanic Americans have a higher prevalence of NAFLD, whereas African Americans have a lower prevalence of NAFLD. The exact contributions of genetic and environmental factors on these differences in the prevalence rates have not been determined. From the spectrum of NAFLD, patients with non-alcoholic steatohepatitis (NASH) are at the highest risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The most recent data regarding the progression of NASH suggest a complex pattern of progression and regression of fibrosis. Factors influencing the progression and regression of NASH have not been fully described. More research is needed to better understand NAFLD in Mexico and Canada.