Wen-Yue Liu1, Kenneth I Zheng2, Xiao-Yan Pan1, Hong-Lei Ma2, Pei-Wu Zhu3, Xi-Xi Wu4, Rafael S Rios2, Giovanni Targher5, Christopher D Byrne6, Xiao-Dong Wang2,7,8, Yong-Ping Chen2,7,8, Ming-Hua Zheng2,7,8. 1. Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 2. NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 3. Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 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, University Hospital Southampton, Southampton General Hospital, Southampton, UK. 7. Institute of Hepatology, Wenzhou Medical University, Wenzhou, China. 8. The Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China.
Abstract
BACKGROUND AND AIM: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) genotype influences clinical/biochemical characteristics in patients with nonalcoholic fatty liver disease (NAFLD), but whether PNPLA3-I148M (rs738409) genotype also influences the diagnostic performance of noninvasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of noninvasive diagnostic tests for NAFLD according to PNPLA3-I148M (rs738409) genotype. METHODS: Fifty-eight healthy controls and 349 patients with biopsy-proven NAFLD were included. Areas under the receiver operating characteristic curve (AUROCs) were calculated to predict hepatic steatosis (fatty liver index and hepatic steatosis index), nonalcoholic steatohepatitis (cytokeratin-18 M30 and M65), and significant fibrosis (≥F2 fibrosis) (fibrosis-4 and BARD), stratifying by rs738409 genotypes (CC and CG + GG groups). RESULTS: Fatty liver index and hepatic steatosis index showed good diagnostic performance for diagnosing steatosis only in the CG + GG group with AUROCs ranging from 0.819 to 0.832. Cytokeratin-18 M30 (AUROC = 0.688) and M65 (AUROC = 0.678) had suboptimal performance for diagnosing nonalcoholic steatohepatitis in the CG + GG group, whereas both had good performance (AUROC = 0.814 and 0.813, respectively) in the CC group. BARD score showed good performance in the CG + GG group compared with the CC group (AUROC = 0.805 and 0.532, respectively). Fibrosis-4 had suboptimal performance in the CG + GG group and good performance in the CC group (AUROC = 0.662 and 0.801, respectively). CONCLUSIONS: Diagnostic performance of noninvasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of noninvasive diagnostic tests for diagnosing NAFLD.
BACKGROUND AND AIM: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) genotype influences clinical/biochemical characteristics in patients with nonalcoholic fatty liver disease (NAFLD), but whether PNPLA3-I148M (rs738409) genotype also influences the diagnostic performance of noninvasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of noninvasive diagnostic tests for NAFLD according to PNPLA3-I148M (rs738409) genotype. METHODS: Fifty-eight healthy controls and 349 patients with biopsy-proven NAFLD were included. Areas under the receiver operating characteristic curve (AUROCs) were calculated to predict hepatic steatosis (fatty liver index and hepatic steatosis index), nonalcoholic steatohepatitis (cytokeratin-18 M30 and M65), and significant fibrosis (≥F2 fibrosis) (fibrosis-4 and BARD), stratifying by rs738409 genotypes (CC and CG + GG groups). RESULTS: Fatty liver index and hepatic steatosis index showed good diagnostic performance for diagnosing steatosis only in the CG + GG group with AUROCs ranging from 0.819 to 0.832. Cytokeratin-18 M30 (AUROC = 0.688) and M65 (AUROC = 0.678) had suboptimal performance for diagnosing nonalcoholic steatohepatitis in the CG + GG group, whereas both had good performance (AUROC = 0.814 and 0.813, respectively) in the CC group. BARD score showed good performance in the CG + GG group compared with the CC group (AUROC = 0.805 and 0.532, respectively). Fibrosis-4 had suboptimal performance in the CG + GG group and good performance in the CC group (AUROC = 0.662 and 0.801, respectively). CONCLUSIONS: Diagnostic performance of noninvasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of noninvasive diagnostic tests for diagnosing NAFLD.
Authors: Wen-Yue Liu; Mohammed Eslam; Kenneth I Zheng; Hong-Lei Ma; Rafael S Rios; Min-Zhi Lv; Gang Li; Liang-Jie Tang; Pei-Wu Zhu; Xiao-Dong Wang; Christopher D Byrne; Giovanni Targher; Jacob George; Ming-Hua Zheng Journal: J Clin Transl Hepatol Date: 2021-02-22
Authors: Ke Xu; Kenneth I Zheng; Pei-Wu Zhu; Wen-Yue Liu; Hong-Lei Ma; Gang Li; Liang-Jie Tang; Rafael S Rios; Giovanni Targher; Christopher D Byrne; Xiao-Dong Wang; Yong-Ping Chen; Ming-Hua Zheng Journal: J Clin Transl Hepatol Date: 2021-07-29