{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:55:58Z","timestamp":1753890958555,"version":"3.41.2"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Constant cellular damage causes a poor prognosis of hepatitis B virus (HBV) infection. Accumulating evidence indicates the cytoprotective properties of bilirubin. Here, we investigated the association of <jats:italic>UDP glucuronosyltransferase family 1 member A1<\/jats:italic> (<jats:italic>UGT1A1<\/jats:italic>), the genetic cause of Gilbert syndrome (GS), a common condition of mild unconjugated bilirubinemia, with HBV infection outcomes.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Patients (n = 2,792) with unconjugated hyperbilirubinemia were screened for HBV infection and host <jats:italic>UGT1A1<\/jats:italic> variations in Ruijin Hospital from January 2015 to May 2023, and those with confirmed HBV exposure were included. The promoter\/exons\/adjacent intronic regions of <jats:italic>UGT1A1<\/jats:italic> were sequenced. HBV infection outcomes were compared between hosts with wild-type and variant-type <jats:italic>UGT1A1<\/jats:italic>. The effect magnitudes of <jats:italic>UGT1A1<\/jats:italic> variations were evaluated using three classification approaches.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In total, 175 patients with confirmed HBV exposure were recruited for final analysis. Age, gender, level of HBV serological markers, and antiviral treatment were comparable between <jats:italic>UGT1A1<\/jats:italic> wild-type and disease-causing variation groups. Five known disease-causing mutations (<jats:italic>UGT1A1*28<\/jats:italic>, <jats:italic>UGT1A1*6<\/jats:italic>, <jats:italic>UGT1A1*27<\/jats:italic>, <jats:italic>UGT1A1*63<\/jats:italic>, and <jats:italic>UGT1A1*7<\/jats:italic>) were detected. The incidence of cirrhosis or hepatocellular carcinoma (LC\/HCC) was significantly lower in <jats:italic>UGT1A1<\/jats:italic> variant hosts than in <jats:italic>UGT1A1<\/jats:italic> wild-type hosts (13.14% vs<jats:italic>.<\/jats:italic> 78.95%, <jats:italic>p &amp;lt; 0.0001<\/jats:italic>). The rarer the <jats:italic>UGT1A1<\/jats:italic> variation a patient possessed, the higher the age at which LC\/HCC was diagnosed (R = 0.34, <jats:italic>p<\/jats:italic> &amp;lt; 0.05). In contrast, patients without cirrhosis achieving HBsAg clearance were identified only in the <jats:italic>UGT1A1<\/jats:italic> variant group (12.32% vs. 0%).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The findings of this study provide insights into the association between preexisting genetically mild bilirubin elevation and viral infection outcome. We showed that the accumulation of <jats:italic>UGT1A1<\/jats:italic> variants or the rarity of the variation is associated with a better prognosis, and the effect magnitude correlates with <jats:italic>UGT1A1<\/jats:italic> deficiency. This study demonstrates the therapeutic potential of host <jats:italic>UGT1A1<\/jats:italic> variations underlying GS against HBV infection outcomes.<\/jats:p>","DOI":"10.3389\/fgene.2023.1265268","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T15:57:25Z","timestamp":1699286245000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic variations underlying Gilbert syndrome and HBV infection outcomes: a cross-sectional study"],"prefix":"10.3389","volume":"14","author":[{"given":"Bilian","family":"Yao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1097\/FPC.0000000000000024","article-title":"PharmGKB summary: very important pharmacogene information for UGT1A1","volume":"24","author":"Barbarino","year":"2014","journal-title":"Pharmacogenet Genomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1002\/hlca.19540370139","article-title":"\u00dcber eine biologische Bedeutung der Gallenfarbstoffe. 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