Obesity and Weight Gain Are Associated With Progression of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

BACKGROUND & AIMS: The effects of weight change on the progression of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) in the general population are unclear. We evaluated the association of weight change and baseline body mass index (BMI) with fibrosis progression, determined by non-invasive measurement of a marker, in young and middle-aged adults with NAFLD. METHODS: We performed a prospective cohort study of 40,700 adults with NAFLD in Korea who received regular health screening examinations and were followed for a median 6.0 years. Weight change was defined as the difference between weights measured at baseline and at a subsequent follow-up visit. The progression from a low to an intermediate or high probability of advanced fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI). RESULTS: During 275,421.5 person-years of follow-up, 5454 subjects with a low APRI progressed to an intermediate or high APRI. Multivariable-adjusted hazard ratios for APRI progression, determined by comparing the first and second weight change quintiles (the weight-loss group) and the fourth and fifth quintiles (weight-gain group) with the third quintile (weight-stable group, reference), were 0.68 (95% CI, 0.62-0.74), 0.86 (95% CI, 0.78-0.94), 1.17 (95% CI, 1.07-1.28), and 1.71 (95% CI, 1.58-1.85), respectively. The multivariable-adjusted hazard ratios for APRI progression were determined by comparing subjects with BMIs of 23-24.9, 25-29.9, and >= 30 with subjects with BMIs of 18.5-22.9 kg/m(2) (reference); these ratios were 1.13 (95% CI, 1.02-1.26), 1.41 (95% CI, 1.28-1.55), and 2.09 (95% CI, 1.86-2.36), respectively. CONCLUSIONS: In a prospective cohort study of 40,700 adults with NAFLD, we found obesity and weight gain to be independently associated with increased risk of fibrosis progression, based on APRI. Maintaining a normal healthy weight and preventing weight gain may help reduce fibrosis progression in individuals with NAFLD.