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CONTEXT: The relationship between rising body mass index (BMI) and prospective risk of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is virtually absent. OBJECTIVE: Determine the extent of the association between BMI and risk of future NAFLD diagnosis, stratifying by sex and diabetes. DESIGN: Two prospective studies using Humedica and Health Improvement Network (THIN) with 1.54 and 4.96 years of follow-up, respectively. SETTING: Electronic health record databases. PARTICIPANTS: Patients with a recorded BMI measurement between 15 and 60 kg/m(2), and smoking status, and 1 year of active status before baseline BMI. Patients with a diagnosis or history of chronic diseases were excluded. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Recorded diagnosis of NAFLD/NASH during follow-up (Humedica International Classification of Diseases, Ninth Revision code 571.8, and read codes for NAFLD and NASH in THIN). RESULTS: Hazard ratios (HRs) were calculated across BMI categories using BMI of 20-22.5 kg/m(2) as the reference category, adjusting for age, sex, and smoking status. Risk of recorded NAFLD/NASH increased linearly with BMI and was approximately 5-fold higher in Humedica (HR = 4.78; 95% confidence interval, 4.17-5.47) and 9-fold higher in THIN (HR = 8.93; 7.11-11.23) at a BMI of 30-32.5 kg/m(2) rising to around 10-fold higher in Humedica (HR = 9.80; 8.49-11.32) and 14-fold higher in THIN (HR = 14.32; 11.04-18.57) in the 37.5- to 40-kg/m(2) BMI category. Risk of NAFLD/NASH was approximately 50% higher in men and approximately double in those with diabetes. CONCLUSIONS: These data quantify the consistent and strong relationships between BMI and prospectively recorded diagnoses of NAFLD/NASH and emphasize the importance of weight reduction strategies for prevention and management of NAFLD.

Original publication




Journal article


J Clin Endocrinol Metab

Publication Date





945 - 952


Adult, Body Mass Index, Diabetes Complications, Electronic Health Records, Female, Humans, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, Prospective Studies, Risk Factors, Sex Factors, Smoking