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Effect of PNPLA3 polymorphism on diagnostic performance of various non-invasive markers for diagnosing and staging NAFLD.
Journal of Gastroenterology and Hepatology 2019 November 2
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 non-invasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of non-invasive diagnostic tests for NAFLD according to PNPLA3-I148M (rs738409) genotype.
METHODS: 58 healthy controls and 349 patients with biopsy-proven NAFLD were included. Areas under operating characteristics (AUROCs) were calculated for predicting hepatic steatosis [fatty liver index (FLI), hepatic steatosis index (HSI)]; NASH [cytokeratin-18 (CK18) M30 and M65] and significant fibrosis (≥F2 fibrosis) [Fibrosis-4 (FIB-4) and BARD], stratifying by rs738409 genotypes (CC and CG+GG groups).
RESULTS: FLI and HSI showed good diagnostic performance for diagnosing steatosis only in the CG+GG group with AUROCs ranging from 0.819 to 0.832 respectively. CK18 M30 (AUROC=0.688) and M65 (AUROC=0.678) had suboptimal performance for diagnosing NASH 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 to the CC group (AUROC=0.805 and 0.532, respectively). FIB-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 non-invasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of non-invasive diagnostic tests for diagnosing NAFLD.
METHODS: 58 healthy controls and 349 patients with biopsy-proven NAFLD were included. Areas under operating characteristics (AUROCs) were calculated for predicting hepatic steatosis [fatty liver index (FLI), hepatic steatosis index (HSI)]; NASH [cytokeratin-18 (CK18) M30 and M65] and significant fibrosis (≥F2 fibrosis) [Fibrosis-4 (FIB-4) and BARD], stratifying by rs738409 genotypes (CC and CG+GG groups).
RESULTS: FLI and HSI showed good diagnostic performance for diagnosing steatosis only in the CG+GG group with AUROCs ranging from 0.819 to 0.832 respectively. CK18 M30 (AUROC=0.688) and M65 (AUROC=0.678) had suboptimal performance for diagnosing NASH 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 to the CC group (AUROC=0.805 and 0.532, respectively). FIB-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 non-invasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of non-invasive diagnostic tests for diagnosing NAFLD.
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