Body Mass Index and Risk of Nonalcoholic Fatty Liver Disease: Two Electronic Health Record Prospective Studies

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.