RF17 | P715 Contribution of Low Muscle Mass and Genetic Factors in NAFLD and Liver Cirrhosis

INTRODUCTION: Both sarcopenia and genetic risk factors are important risk factors for non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the independent effects of low muscle mass and genetic risk factors in the development of NAFLD and liver cirrhosis (LC) in the Korean population. Method: A prospective community-based cohort consisted of adults with age 40–70 years were followed-up biennially from 2001–2002 to 2017–2018. NAFLD was defined as hepatic steatosis index of ≥36, and liver cirrhosis (LC) was defined as a fibrosis-4 index score of ≥1.3. The subjects were divided into four groups according to body mass index (BMI)-adjusted muscle mass. Cox proportional hazards models incorporating age, sex, BMI≥ 25 kg/m(2), metabolic syndrome, and PNPLA3, and TM6SF2 risk alleles were used to assess the independent determinants for the incident NAFLD and development of LC among individuals with NAFLD at baseline. RESULTS: Among the 4,038 participants without NAFLD at baseline, 920 (22.8%) developed NAFLD during the follow-up. Both the TM6SF2 risk alleles (hazard ratio [HR]. 1.19, [95% confidence interval (CI), 1.00–1.40], P=0.044) and muscle mass index quartiles (Q) (HR per 1 Q, 1.18, 95% CI, 1.11–1.27, P<0.001) were associated with development of NAFLD in the fully adjusted model. Of the 1,442 patients with NAFLD at baseline, LC was eventually confirmed in 552 (38.3%) patients. Only the PNPLA3 risk variant, but not the TM6SF2 genotype nor muscle mass index, was an independent risk factor for developing LC among NAFLD subjects (HR 1.22, 95% CI 1.08–1.38, P=0.001) CONCLUSION: Both the lower muscle mass index and genetic risk variants are important contributors in the development of NAFLD. In patients already diagnosed with NALFD however, PNPLA3 conferred a greater risk for the progression to LC than lower muscle mass. Presentation: No date and time listed