{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:09:08Z","timestamp":1788577748946,"version":"build-2803163510"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,11,3]],"date-time":"2019-11-03T00:00:00Z","timestamp":1572739200000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1060811"],"award-info":[{"award-number":["1060811"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>There is increasing evidence to suggest that, among those with chronic hepatitis B virus infection, the natural history and rate of progression to cirrhosis and hepatocellular carcinoma is influenced by hepatitis B virus genotype. The unique hepatitis B virus genotype C4 circulates among Indigenous Australians. The aim of this work is to describe the process of establishing this cohort and review the first 6 years of available data in an effort to understand the real-world clinical care and natural history of this subgenotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Method<\/jats:title>\n                  <jats:p>We followed a longitudinal cohort of Indigenous Australians from the Northern Territory of Australia with established subgenotype C4 infections. We assigned phases of disease according to Gastroenterological Society of Australia and Asian Pacific Association for the Study of the Liver criteria using clinical and laboratory information that had been collected for clinical management.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 193 patients followed over a median of 38 months, 58 (30%) individuals transitioned from 1 disease phase to another, 10 (5%) cleared hepatitis B e antigen, and 6 cleared hepatitis B surface antigen (3%). In this relatively young cohort (median age 40.3 years), 26 (13%) had cirrhosis by the end of the follow up period, with the majority of these being in the immune control phase of disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In this cohort of hepatitis B subgenotype C4 patients, we report an aggressive and dynamic clinical phenotype. High rates of cirrhosis at a young age appear to occur in the early phases of disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofz469","type":"journal-article","created":{"date-parts":[[2019,11,3]],"date-time":"2019-11-03T06:07:16Z","timestamp":1572761236000},"source":"Crossref","is-referenced-by-count":8,"title":["Towards Genotype-Specific Care for Chronic Hepatitis B: The First 6 Years Follow Up From the CHARM Cohort Study"],"prefix":"10.1093","volume":"6","author":[{"given":"Jane","family":"Davies","sequence":"first","affiliation":[{"name":"Global and Tropical Health, Menzies School of Health Research, Darwin, Northern Territory, Australia"},{"name":"Division of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Littlejohn","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalind","family":"Edwards","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitina","family":"Sozzi","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Jackson","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Mcguire","sequence":"additional","affiliation":[{"name":"Global and Tropical Health, Menzies School of Health Research, Darwin, Northern Territory, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Binks","sequence":"additional","affiliation":[{"name":"Global and Tropical Health, Menzies School of Health Research, Darwin, Northern Territory, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin C","family":"Cowie","sequence":"additional","affiliation":[{"name":"World Health Organization Collaborating Centre for Viral Hepatitis, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"},{"name":"Department of Medicine, Royal Melbourne Hospital, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Locarnini","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9864-5699","authenticated-orcid":false,"given":"Joshua S","family":"Davis","sequence":"additional","affiliation":[{"name":"Global and Tropical Health, Menzies School of Health Research, Darwin, Northern Territory, Australia"},{"name":"Department of Infectious Diseases, John Hunter Hospital, Newcastle, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven Y C","family":"Tong","sequence":"additional","affiliation":[{"name":"Global and Tropical Health, Menzies School of Health Research, Darwin, Northern Territory, Australia"},{"name":"Victorian Infectious Disease Service, The Royal Melbourne Hospital, Melbourne, Victoria, Australia"},{"name":"Doherty Department University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,3]]},"reference":[{"key":"2020082404372468200_CIT0001","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1007\/s12072-008-9112-z","article-title":"The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B","volume":"3","author":"McMahon","year":"2009","journal-title":"Hepatol Int"},{"key":"2020082404372468200_CIT0002","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1055\/s-0033-1345716","article-title":"Global perspective on the natural history of chronic hepatitis B: role of hepatitis B virus genotypes A to J","volume":"33","author":"Liu","year":"2013","journal-title":"Semin Liver Dis"},{"key":"2020082404372468200_CIT0003","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jhep.2005.03.018","article-title":"Genotype C hepatitis B virus infection is associated with a higher risk of reactivation of hepatitis B and progression to cirrhosis than genotype B: a longitudinal study of hepatitis B e antigen-positive patients with normal aminotransferase levels at baseline","volume":"43","author":"Chu","year":"2005","journal-title":"J Hepatol"},{"key":"2020082404372468200_CIT0004","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.cgh.2009.08.004","article-title":"Hepatitis B virus genotype C is associated with more severe liver fibrosis than genotype B","volume":"7","author":"Chan","year":"2009","journal-title":"Clin Gastroenterol 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Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma","volume":"100","author":"Yang","year":"2008","journal-title":"J Natl Cancer Inst"},{"key":"2020082404372468200_CIT0007","doi-asserted-by":"crossref","first-page":"e47271","DOI":"10.1371\/journal.pone.0047271","article-title":"Subgenotyping of genotype C hepatitis B virus: correcting misclassifications and identifying a novel subgenotype","volume":"7","author":"Shi","year":"2012","journal-title":"PLOS ONE"},{"key":"2020082404372468200_CIT0008","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/jmv.10534","article-title":"Hepatitis B virus genotypes and spontaneous hepatitis B e antigen seroconversion in Taiwanese hepatitis B carriers","volume":"72","author":"Kao","year":"2004","journal-title":"J Med Virol"},{"key":"2020082404372468200_CIT0009","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1053\/gast.2002.33588","article-title":"Hepatitis B virus genotype B is 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