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Recently, carriage of the rs6834314 G allele, which is in high linkage with rs72613567 of 17\u2010beta\u2010hydroxysteroid dehydrogenase 13 (<jats:italic>HSD17B13<\/jats:italic>), was reported to be associated with a reduced risk of liver injury in NAFLD patients. We estimated the impact of these genetic variants on hepatic fibrosis in Japanese patients with NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed the associations of these genetic variants with liver histology in 290 Japanese patients with biopsy\u2010proven NAFLD diagnosed during 2002\u20102019. During follow\u2010up, 14 patients (4.8%) developed hepatocellular carcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Prevalences of the <jats:italic>PNPLA3<\/jats:italic> rs738409 genotypes were 0.17 for CC, 0.41 for CG, 0.42 for GG, and those for <jats:italic>HSD17B13<\/jats:italic> rs6834314 were 0.54 for AA, 0.39 for AG and 0.07 for GG. There was no significant interaction between the <jats:italic>PNPLA3<\/jats:italic> and <jats:italic>HSD17B13<\/jats:italic> genotypes. Prevalences of advanced fibrosis according to <jats:italic>PNPLA3\/HSD17B13<\/jats:italic> genotypes were 0.16 for CC,CG\/AG,GG, 0.20 for CC,CG\/AA, 0.30 for GG\/AG,GG and 0.37 for GG\/AA. Multivariate analysis identified <jats:italic>PNPLA3<\/jats:italic> GG as a predictor of advanced fibrosis (stage 3\/4) in carriers of <jats:italic>HSD17B13<\/jats:italic> AA (odds ratio 2.4, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.041), but not <jats:italic>HSD17B13<\/jats:italic> AG\/GG (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.776). The <jats:italic>HSD17B13<\/jats:italic> genotype G was significantly associated with lower prevalences of severe inflammation and ballooning and tended to be associated with a higher prevalence of advanced steatosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In Japanese patients with NAFLD, carriage of the <jats:italic>HSD17B13<\/jats:italic> rs6834314 G allele attenuated the effect of the <jats:italic>PNPLA3<\/jats:italic> rs738409 GG genotype on advanced hepatic fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14495","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T06:19:38Z","timestamp":1588054778000},"page":"1686-1692","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Attenuated effect of PNPLA3 on hepatic fibrosis by HSD17B13 in Japanese patients with non\u2010alcoholic fatty liver 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