The Natural History of Nonalcoholic Fatty Liver Disease with Normal Body Mass Index: a Population-Based Study.

BACKGROUND AND AIMS: The natural history of lean nonalcoholic fatty liver disease (NAFLD) is not well understood. Consequently, patient counseling and disease management are limited. We aimed to compare the natural history of lean, overweight and obese NAFLD in a US population with long term follow-up.

METHODS: All adults diagnosed with NAFLD in Olmsted County, MN between 1996-2016 were identified and all subsequent medical events were ascertained using a medical record linkage system. Subjects were divided based on body mass index (BMI) at NAFLD diagnosis into 3 groups: normal, overweight, and obese. The probability to develop cirrhosis, decompensation, malignancies, cardiovascular events or death among the 3 groups was estimated using the Aalen-Johansen method, treating death as a competing risk. The impact of BMI categories on these outcomes was explored using Cox proportional hazards regression analysis.

RESULTS: A total of 4,834 NAFLD individuals were identified: 414 normal BMI, 1,189 overweight and 3,231 obese. Normal BMI-NAFLD individuals were characterized by a higher proportion of women (66 vs 47%) and lower prevalence of metabolic comorbidities than the other 2 groups. In reference to obese, those with normal BMI NAFLD had a nonsignificant trend towards lower risk of cirrhosis (HR=0.33, 95%CI 0.1-1.05). There were no significant differences in the risk of decompensation (HR=0.79, 95%CI 0.11-5.79), cardiovascular events (HR=1.05, 95%CI 0.73-1.51) or malignancy (HR=0.87, 95%CI 0.51-1.48). Compared to obese, normal BMI NAFLD had higher risk of all-cause mortality (HR=1.96, 95%CI 1.52-2.51).

CONCLUSIONS: NAFLD with normal BMI is associated with a healthier metabolic profile and possibly a lower risk of liver disease progression but similar risk of cardiovascular disease and malignancy than obese NAFLD.