Risk of hepatocellular carcinoma according to body mass index and waist circumference in nonalcoholic fatty liver disease.

Background: The association between adiposity parameters and incident hepatocellular carcinoma (HCC) in individuals with nonalcoholic fatty liver disease (NAFLD) is yet to be evaluated.

Aim: To investigate the risk of HCC according to body mass index (BMI) and waist circumference (WC) in people with NAFLD.

Methods: This population-based cohort study included Korean National Health Insurance Service examination participants with NAFLD (n = 1110773). NAFLD was defined as a fatty liver index of ≥ 30. The risk of HCC was determined by Cox proportional hazards regression according to BMI and WC after adjusting for age, sex, health behaviors, income, comorbidities, and WC or BMI.

Results: HCC was diagnosed in 4773 (0.43%) participants during a median follow-up of 10.3 years. A U-shaped association between BMI or WC and HCC was observed, with the highest risk observed in the lowest BMI and WC groups. Compared to normal BMI, the adjusted hazard ratio (aHR) of the underweight BMI group was 2.02 [95% confidence interval (CI): 1.25-3.28]. The lowest risk was found in groups with overweight BMI (aHR = 0.67, 95%CI: 0.60-0.73; reference: normal BMI) and WC: 85-89.9/80-84.9 cm for men/women (aHR = 0.55, 95%CI: 0.49-0.63; reference: < 80/< 75 cm). Subgroup analyses of age, sex, health behaviors, and fatty liver index showed consistent results.

Conclusion: The development of HCC shows a U-shaped relationship with BMI and WC in people with NAFLD, with the highest risk in underweight individuals.