{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:05:39Z","timestamp":1779883539101,"version":"3.53.1"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Covalently closed circular DNA (cccDNA), a stable episomal form of the hepatitis B virus (HBV) genome, functions as the transcriptional template for viral replication and persistence, posing a major barrier to HBV cure. While host DNA repair factors such as DDB2 and DNA polymerase delta (Pol \u03b4) have been involved in cccDNA regulation in\u00a0vitro, clinical validation remains limited. This study investigated the role of DDB2 and Pol \u03b4 in cccDNA maintenance using HBV\u2010infected cell models and liver tissues from patients with HBV\u2010related and occult HBV infection (OBI)\u2010associated hepatocellular carcinoma (HCC). HepG2\u2010NTCP cells infected with HBV were transfected with siRNAs targeting DDB2 or Pol \u03b4, followed by quantification of intracellular cccDNA using droplet digital PCR (ddPCR). In liver tissues from HBV\u2010HCC and OBI\u2010HCC patients, the expression of DDB2 and Pol \u03b4 was assessed, while intrahepatic HBV DNA and cccDNA were measured by qPCR and ddPCR. Serum HBcrAg levels were evaluated using the iTACT\u2010HBcrAg assay. Knockdown of DDB2 and Pol \u03b4 significantly reduced intracellular cccDNA levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.010 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006, respectively). In patient tissues, intrahepatic HBV DNA and cccDNA were markedly lower in OBI\u2010HCC compared to HBV\u2010HCC, despite comparable DDB2 and Pol \u03b4 expression. HBcrAg was detectable in 91.3% of HBV\u2010HCC versus only 23.8% of OBI\u2010HCC cases (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). DDB2 expression correlated with intrahepatic viral markers in both groups and with HBcrAg only in HBV\u2010HCC. These findings suggest that DDB2 is involved in cccDNA persistence and represents potential therapeutic targets for both overt and occult HBV\u2010related HCC.\n                  <\/jats:p>","DOI":"10.1111\/jvh.70182","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:00:44Z","timestamp":1777957244000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Host Factors DDB2 and DNA Polymerase Delta Are Linked to cccDNA Persistence in Hepatitis B Virus and Occult Hepatitis B Virus\u2010Related Hepatocellular Carcinoma"],"prefix":"10.1111","volume":"33","author":[{"given":"Kanyakorn","family":"Singsung","sequence":"first","affiliation":[{"name":"Center of Excellence in Kidney\u2010Liver\u2010Microbiota, Department of Biochemistry, Faculty of Medicine Chulalongkorn University  Bangkok 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5415-510X","authenticated-orcid":false,"given":"Natthaya","family":"Chuaypen","sequence":"additional","affiliation":[{"name":"Center of Excellence in Kidney\u2010Liver\u2010Microbiota, Department of Biochemistry, Faculty of Medicine Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pongserath","family":"Sirichindakul","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine Chulalongkorn University, King Chulalongkorn Memorial Hospital  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20101253(22)00386\u20107"},{"key":"e_1_2_13_3_1","volume-title":"Hepatitis B","author":"Organisation 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