{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T10:53:13Z","timestamp":1781607193920,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005699","name":"Universit\u00e0 degli Studi del Piemonte Orientale","doi-asserted-by":"publisher","award":["2016"],"award-info":[{"award-number":["2016"]}],"id":[{"id":"10.13039\/501100005699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gastroenterology Research and Practice"],"published-print":{"date-parts":[[2020,4,24]]},"abstract":"<jats:p>A single-nucleotide polymorphism causing a C to G change in the <jats:italic>PNPLA3<\/jats:italic> gene (rs738409) is associated with disease severity and development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease; the insertion variant rs72613567:TA of the 17<jats:italic>\u03b2<\/jats:italic>-hydroxysteroid dehydrogenase type 13 (<jats:italic>HSD17B13<\/jats:italic>) mitigates this detrimental effect. Our aim was to evaluate if the same holds true in chronic hepatitis C virus infection (HCV). With a case control retrospective study design, we selected 110 patients who developed HCC on a background of HCV infection, matching each patient for sex and age (\u00b130 months) to three HCV-infected, non-HCC patients. All participants underwent genotyping for <jats:italic>PNPLA3<\/jats:italic> and <jats:italic>HSD17B13<\/jats:italic> gene variants. Both univariate and multivariate analyses of risk factors for advanced disease and HCC were performed. Carriage of <jats:italic>PNPLA3<\/jats:italic> G<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mo>\u2217<\/mml:mo><\/mml:math> allele was associated with a trend of progressively more severe liver disease, from mild fibrosis to significant fibrosis, cirrhosis, and HCC (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.007<\/mml:mn><\/mml:math>). When the <jats:italic>HSD17B13:TA<\/jats:italic> status of these patients was taken into account, the abovementioned trend was strengthened among <jats:italic>HSD17B13<\/jats:italic> major allele homozygotes and completely blunted among carriers of the minor allele (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.0003<\/mml:mn><\/mml:math> and 0.953, respectively). In a conditional logistic regression model including diabetes and AST to platelet ratio index among predictor variables, the unfavourable genetic profile characterized by the coexistence of the <jats:italic>PNPLA3<\/jats:italic> minor allele and <jats:italic>HSD17B13<\/jats:italic> major allele (vs. all other possible combinations) was an independent risk factor for HCC (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mtext>OR<\/mml:mtext><mml:mo>=<\/mml:mo><mml:mn>2.00<\/mml:mn><\/mml:math>, 95% CI: 1.23-3.26) together with a history of alcohol abuse. In conclusion, carriage of the combination <jats:italic>PNPLA3<\/jats:italic> minor allele and <jats:italic>HSD17B13<\/jats:italic> major allele may represent a risk factor for HCC among HCV-infected patients. The interplay between the two genes may explain some of the controversy on this topic and may be exploited to stratify HCC risk in hepatitis C.<\/jats:p>","DOI":"10.1155\/2020\/4216451","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T23:30:59Z","timestamp":1587771059000},"page":"1-8","source":"Crossref","is-referenced-by-count":13,"title":["Interplay of <i>PNPLA3<\/i> and <i>HSD17B13<\/i> Variants in Modulating the Risk of Hepatocellular Carcinoma among Hepatitis C Patients"],"prefix":"10.1155","volume":"2020","author":[{"given":"Carla","family":"De Benedittis","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale (UPO), Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-8736","authenticated-orcid":true,"given":"Mattia","family":"Bellan","sequence":"additional","affiliation":[{"name":"Department of Translational 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Ramana","family":"Mallela","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale (UPO), Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Ravanini","sequence":"additional","affiliation":[{"name":"AOU Maggiore della Carit\u00e0, Virology Unit, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Ceriani","sequence":"additional","affiliation":[{"name":"Department of Medicine, AOU Maggiore della Carit\u00e0, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Fangazio","sequence":"additional","affiliation":[{"name":"Department of Medicine, AOU Maggiore della Carit\u00e0, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Paolo","family":"Sainaghi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del 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