Xiao-Yan Pan1, Wen-Yue Liu1, Pei-Wu Zhu2, Gang Li3, Liang-Jie Tang3, Feng Gao4, Ou-Yang Huang3, Hai-Yang Yuan3, Giovanni Targher5, Christopher D Byrne6,7, Xiao-Dong Wang8, Ming-Hua Zheng9,10,11. 1. Department of Endocrinology and Metabolic Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 2. Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 3. NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China. 4. Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 5. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. 6. Southampton National Institute for Health Research Biomedical Research Centre, Southampton General Hospital, University Hospital Southampton, Southampton, UK. 7. Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK. 8. Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China. 9. NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China. zhengmh@wmu.edu.cn. 10. Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China. zhengmh@wmu.edu.cn. 11. Institute of Hepatology, Wenzhou Medical University, Wenzhou, China. zhengmh@wmu.edu.cn.
Abstract
BACKGROUND/PURPOSE OF THE STUDY: Although low skeletal muscle mass is associated with non-alcoholic fatty liver disease (NAFLD), it is currently uncertain whether there are associations between weight-adjusted appendicular skeletal muscle (ASM%), severity of histological features of NAFLD, and the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. Our aim was to test for a possible influence of the PNPLA3 rs738409 variant on the association between ASM% and severity of NAFLD histological features. METHODS: We enrolled 401 Chinese male with biopsy-proven NAFLD. Using a bioelectrical-impedance body composition analyzer (BIA, Inbody 720, Japan Inc., Tokyo), we calculated the ASM% as the percentage of total appendicular skeletal muscle mass (ASM, kg)/total body mass (kg) × 100. RESULTS: Compared to those with high ASM%, patients with low ASM% (≤ 30.6, i.e., the median value of distribution of the whole sample) had a greater severity of individual histological features of NAFLD. These patients also had a higher risk of severe steatosis and non-alcoholic steatohepatitis (NASH) (adjusted-odds ratio [OR] 2.34, 95% CI 1.39-3.93, and adjusted-OR 2.22, 95% CI 1.30-3.77) even after adjusting for age, body mass index, diabetes, and serum creatinine levels. Carriage of the G allele of PNPLA3 rs738409 plus low ASM% was associated with a higher risk of severe steatosis and presence of liver fibrosis (OR 3.02, 95% CI 1.46-6.26, p = 0.003 and OR 2.18, 95% CI 1.03-4.60, p = 0.041 respectively), and there was a non-significant but borderline increased risk of NASH (OR 2.00, 95% CI 0.98-4.06, p = 0.056). CONCLUSIONS: Low ASM% and the presence of a G allele within PNPLA3 rs738409 is associated with more severe histological features of NAFLD.
BACKGROUND/PURPOSE OF THE STUDY: Although low skeletal muscle mass is associated with non-alcoholic fatty liver disease (NAFLD), it is currently uncertain whether there are associations between weight-adjusted appendicular skeletal muscle (ASM%), severity of histological features of NAFLD, and the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. Our aim was to test for a possible influence of the PNPLA3 rs738409 variant on the association between ASM% and severity of NAFLD histological features. METHODS: We enrolled 401 Chinese male with biopsy-proven NAFLD. Using a bioelectrical-impedance body composition analyzer (BIA, Inbody 720, Japan Inc., Tokyo), we calculated the ASM% as the percentage of total appendicular skeletal muscle mass (ASM, kg)/total body mass (kg) × 100. RESULTS: Compared to those with high ASM%, patients with low ASM% (≤ 30.6, i.e., the median value of distribution of the whole sample) had a greater severity of individual histological features of NAFLD. These patients also had a higher risk of severe steatosis and non-alcoholic steatohepatitis (NASH) (adjusted-odds ratio [OR] 2.34, 95% CI 1.39-3.93, and adjusted-OR 2.22, 95% CI 1.30-3.77) even after adjusting for age, body mass index, diabetes, and serum creatinine levels. Carriage of the G allele of PNPLA3 rs738409 plus low ASM% was associated with a higher risk of severe steatosis and presence of liver fibrosis (OR 3.02, 95% CI 1.46-6.26, p = 0.003 and OR 2.18, 95% CI 1.03-4.60, p = 0.041 respectively), and there was a non-significant but borderline increased risk of NASH (OR 2.00, 95% CI 0.98-4.06, p = 0.056). CONCLUSIONS: Low ASM% and the presence of a G allele within PNPLA3 rs738409 is associated with more severe histological features of NAFLD.