{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:37:09Z","timestamp":1792103829167,"version":"4.4.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Chronic hepatitis B virus (HBV) infection is the leading risk factor for hepatocellular carcinoma (HCC). The aim of this study was to explore the incidence of HCC in a cohort of subjects with HBV and correlate with HBV treatment current guidance. We identified 2846 subjects with HBV over the study period. HCC was diagnosed in 386 of 2846 (14%) subjects; 209 of 386 (54%) were on nucleos(t)ide analogue (NA) therapy at time of HCC diagnosis, and 177 of 386 (46%) were not on NA therapy. Of the 177 subjects not on NAs who developed HCC during follow\u2010up, 153 of 177 (86%) had cirrhosis. Within the 177 subjects not on NAs, 158 of 177 (89%) had undetectable HBV DNA, 10 of 177 (6%) had detectable HBV DNA\u2009&lt;\u20092000\u2009IU\/L, and 9 of 177 (5%) had HBV DNA\u2009&gt;\u20092000\u2009IU\/L. Of those with cirrhosis and undetectable HBV DNA, 115 of 141 had compensated cirrhosis, and 26 of 141 had decompensated cirrhosis. Significant predictors of HCC on time to event analysis included cirrhosis (hazard ratio [HR] 10, 95% confidence interval [CI] 5.8\u201317.5; <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0&lt;\u20090.001), alanine aminotransferase level (HR 1.004, 95% CI 1.002\u20131.006; <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0&lt;\u20090.001), age (HR 1.04, 95% CI 1.03\u20131.06; <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0&lt;\u20090.001), (HR 1.9, 95% CI 1.2\u20133.1; <jats:italic toggle=\"yes\">p<\/jats:italic> 0.007), and nonalcoholic fatty liver disease (HR 1.7, 95% CI 1.1\u20132.8; <jats:italic toggle=\"yes\">p<\/jats:italic> 0.02). Kaplan\u2013Meier analysis demonstrated the cumulative incidence of HCC in subjects with compensated cirrhosis receiving NA therapy was significantly lower compared to subjects with compensated cirrhosis outside current HBV treatment practice guidance (undetectable HBV DNA) (32% vs. 51%; <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0&lt;\u20090.001). <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Those with untreated compensated cirrhosis with undetectable HBV DNA who do not meet current guidance for treatment had higher rates of HCC than those with compensated cirrhosis and suppressed HBV DNA by NA therapy. This study highlights the need for earlier diagnosis and treatment of HBV.<\/jats:p>","DOI":"10.1002\/hep4.2064","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T09:41:54Z","timestamp":1661420514000},"page":"3052-3061","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Incidence of hepatocellular carcinoma in chronic hepatitis B virus infection in those not meeting criteria for antiviral therapy"],"prefix":"10.1097","volume":"6","author":[{"given":"Omar","family":"Alshuwaykh","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tami","family":"Daugherty","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9588-9364","authenticated-orcid":false,"given":"Aparna","family":"Goel","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8819-7511","authenticated-orcid":false,"given":"Renumathy","family":"Dhanasekaran","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Tara","family":"Ghaziani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3609-8586","authenticated-orcid":false,"given":"Aijaz","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepti","family":"Dronamraju","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhika","family":"Kumari","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3874-6612","authenticated-orcid":false,"given":"Allison","family":"Kwong","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-4989","authenticated-orcid":false,"given":"Mindie","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3030-860X","authenticated-orcid":false,"given":"W. Ray","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-4485","authenticated-orcid":false,"given":"Paul Yien","family":"Kwo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Stanford University Medical Center,Stanford,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"hep42064-bib-0001-20241104","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41575-019-0186-y","article-title":"A global view of hepatocellular carcinoma: trends, risk, prevention and management","volume":"16","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"hep42064-bib-0002-20241104","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1001\/jama.295.1.65","article-title":"Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level","volume":"295","year":"2006","journal-title":"JAMA"},{"key":"hep42064-bib-0003-20241104","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1056\/NEJMoa013215","article-title":"Hepatitis B e antigen and the risk of hepatocellular carcinoma","volume":"347","year":"2002","journal-title":"N Engl J Med"},{"key":"hep42064-bib-0004-20241104","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1056\/NEJMoa033364","article-title":"Lamivudine for patients with chronic hepatitis B and advanced liver disease","volume":"351","year":"2004","journal-title":"N Engl J Med"},{"key":"hep42064-bib-0005-20241104","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1111\/j.1365-2036.2008.03816.x","article-title":"Meta\u2010analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma","volume":"28","year":"2008","journal-title":"Aliment Pharmacol Ther"},{"key":"hep42064-bib-0006-20241104","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.jhep.2015.01.002","article-title":"Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy","volume":"62","year":"2015","journal-title":"J Hepatol"},{"key":"hep42064-bib-0007-20241104","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","year":"2018","journal-title":"Hepatology"},{"key":"hep42064-bib-0008-20241104","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.28156","article-title":"AASLD guidelines for treatment of chronic hepatitis B","volume":"63","year":"2016","journal-title":"Hepatology"},{"key":"hep42064-bib-0009-20241104","first-page":"1766","article-title":"Treatment algorithm for managing chronic hepatitis B virus infection in the United States: 2021 update","volume":"28","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"hep42064-bib-0010-20241104","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection","volume":"67","year":"2017","journal-title":"J Hepatol"},{"key":"hep42064-bib-0011-20241104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12072-015-9675-4","article-title":"Asian\u2010Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update","volume":"10","year":"2016","journal-title":"Hepatol Int"},{"key":"hep42064-bib-0012-20241104","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/liv.13142","article-title":"Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: a systematic review and meta\u2010analysis","volume":"36","year":"2016","journal-title":"Liver Int"},{"key":"hep42064-bib-0013-20241104","article-title":"Effective viral suppression is necessary to reduce hepatocellular carcinoma development in cirrhotic patients with chronic hepatitis B: Results of a 10\u2010year follow up","volume":"96","year":"2017","journal-title":"Medicine"},{"key":"hep42064-bib-0014-20241104","article-title":"Risk of hepatocellular carcinoma remains high in patients with HBV\u2010related decompensated cirrhosis and long\u2010term antiviral therapy","volume":"2020","year":"2020","journal-title":"Can J Gastroenterol Hepatol"},{"key":"hep42064-bib-0015-20241104","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1111\/j.1440-1746.2011.06695.x","article-title":"Natural history of chronic hepatitis B REVEALed","volume":"26","year":"2011","journal-title":"J Gastroenterol Hepatol"},{"key":"hep42064-bib-0016-20241104","doi-asserted-by":"crossref","first-page":"406","DOI":"10.14309\/ajg.0000000000000490","article-title":"Earlier alanine aminotransferase normalization during antiviral treatment is independently associated with lower risk of hepatocellular carcinoma in chronic hepatitis B","volume":"115","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"hep42064-bib-0017-20241104","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1007\/s10620-016-4431-8","article-title":"Rapid alanine aminotransferase normalization with entecavir and hepatocellular carcinoma in hepatitis B virus\u2013associated cirrhosis","volume":"62","year":"2017","journal-title":"Dig Dis Sci"},{"key":"hep42064-bib-0018-20241104","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.jhep.2018.05.009","article-title":"Normal on\u2010treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B","volume":"69","year":"2018","journal-title":"J Hepatol"},{"key":"hep42064-bib-0019-20241104","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1136\/gutjnl-2013-306409","article-title":"Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease","volume":"63","year":"2014","journal-title":"Gut"},{"key":"hep42064-bib-0020-20241104","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1111\/jvh.13185","article-title":"The risk of hepatocellular carcinoma among chronic hepatitis B virus\u2010infected patients outside current treatment criteria","volume":"26","year":"2019","journal-title":"J Viral Hepat"},{"key":"hep42064-bib-0021-20241104","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jhep.2019.11.003","article-title":"Guidance for design and endpoints of clinical trials in chronic hepatitis B\u2014report from the 2019 EASL\u2010AASLD HBV Treatment Endpoints Conference","volume":"72","year":"2020","journal-title":"J Hepatol"}],"container-title":["Hepatology Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep4.2064","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep4.2064","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/hep4.2064","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T08:01:25Z","timestamp":1730707285000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/hep4.2064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,25]]},"references-count":21,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.1002\/hep4.2064","relation":{},"ISSN":["2471-254X","2471-254X"],"issn-type":[{"value":"2471-254X","type":"print"},{"value":"2471-254X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,25]]},"assertion":[{"value":"2022-03-14","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-09","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}