Disease progression & treatment need in sub-genotype C4 hepatitis B infection: a retrospective cohort study in the Northern Territory, Australia
Abstract Background In the Northern Territory (NT) of Australia, First Nations people with chronic hepatitis B (CHB) are infected with a unique sub-genotype, C4, which contains mutations linked to progressive fibrosis and hepatocellular carcinoma. This cohort study aimed to investigate disease progr...
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2025-07-01
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| author | Genevieve E. Martin Kelly Hosking Kelly Banz Catherine Gargan Geoff Stewart Belinda Greenwood-Smith Penelope Ramsay Jaclyn Tate-Baker Christine Connors Paula Binks Melita McKinnon Prashanti Manchikanti George Garambaka Gurruwiwi Nicole Allard Ashleigh Qama Jessica Michaels Emily Vintour-Cesar Robert Batey Catherine Marshall Peter Nihill Tammy-Allyn Fernandes Karen Fuller Steven Y. C. Tong David Boettiger Benjamin Cowie Joshua S. Davis Sarah Mariyalawuy Bukulatjpi Jane Davies on behalf of the Hep B PAST Partnership |
| author_facet | Genevieve E. Martin Kelly Hosking Kelly Banz Catherine Gargan Geoff Stewart Belinda Greenwood-Smith Penelope Ramsay Jaclyn Tate-Baker Christine Connors Paula Binks Melita McKinnon Prashanti Manchikanti George Garambaka Gurruwiwi Nicole Allard Ashleigh Qama Jessica Michaels Emily Vintour-Cesar Robert Batey Catherine Marshall Peter Nihill Tammy-Allyn Fernandes Karen Fuller Steven Y. C. Tong David Boettiger Benjamin Cowie Joshua S. Davis Sarah Mariyalawuy Bukulatjpi Jane Davies on behalf of the Hep B PAST Partnership |
| author_sort | Genevieve E. Martin |
| collection | DOAJ |
| description | Abstract Background In the Northern Territory (NT) of Australia, First Nations people with chronic hepatitis B (CHB) are infected with a unique sub-genotype, C4, which contains mutations linked to progressive fibrosis and hepatocellular carcinoma. This cohort study aimed to investigate disease progression in C4 sub-genotype infection and estimate how many untreated individuals may benefit from antiviral therapy with broadening treatment indications. Methods Included individuals were part of Hep B PAST, a co-designed program to improve the cascade of care for people living with CHB in the NT. Disease phase and cirrhotic status were determined algorithmically using clinical and laboratory data at two time points. Loss of HBV antigens was assessed longitudinally. Treatment need was assessed cross-sectionally in the cohort at study completion. Key outcomes were estimated rates of HBsAg/HBeAg loss in sub-genotype C4 infection and quantification of how many untreated individuals qualify for therapy under current Australian and expanded global treatment guidelines. Results HBsAg and HBeAg loss occurred at a rate of 1·04 and 8·06 events/100 person-years respectively (7342·6 and 545·6 years follow up). 783 people living with CHB were included (40% female, median age 48 years). Of these, 16% had cirrhosis (an additional 6% having FibroScan > 7 kPa, meaning 22% had cirrhosis or significant fibrosis) and 25% were prescribed antivirals. Only 6·7% of untreated individuals were treatment eligible under current guidelines. Using the 2024 World Health Organisation guidelines, this increased to 50% due mostly to fibrosis and population prevalence of diabetes. Conclusions Despite advanced liver disease in people living with CHB in the NT, rates of antigen loss in sub-genotype C4 hepatitis B infection are similar to other genotypes. Further work is needed to understand drivers of cirrhosis and significant fibrosis in this population. |
| format | Article |
| id | doaj-art-1e66356b1c7645e69acd596c6509cac9 |
| institution | DOAJ |
| issn | 1471-2334 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-1e66356b1c7645e69acd596c6509cac92025-08-20T03:03:24ZengBMCBMC Infectious Diseases1471-23342025-07-0125111110.1186/s12879-025-11213-wDisease progression & treatment need in sub-genotype C4 hepatitis B infection: a retrospective cohort study in the Northern Territory, AustraliaGenevieve E. Martin0Kelly Hosking1Kelly Banz2Catherine Gargan3Geoff Stewart4Belinda Greenwood-Smith5Penelope Ramsay6Jaclyn Tate-Baker7Christine Connors8Paula Binks9Melita McKinnon10Prashanti Manchikanti11George Garambaka Gurruwiwi12Nicole Allard13Ashleigh Qama14Jessica Michaels15Emily Vintour-Cesar16Robert Batey17Catherine Marshall18Peter Nihill19Tammy-Allyn Fernandes20Karen Fuller21Steven Y. C. Tong22David Boettiger23Benjamin Cowie24Joshua S. Davis25Sarah Mariyalawuy Bukulatjpi26Jane Davies27on behalf of the Hep B PAST PartnershipGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin UniversityGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin UniversityNorthern Territory HealthNorthern Territory HealthNorthern Territory HealthNorthern Territory HealthNorthern Territory HealthNorthern Territory HealthNorthern Territory HealthGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin UniversityGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin UniversityMiwatj Health Aboriginal CorporationGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin UniversityWHO Collaborating Centre for Viral Hepatitis, Peter Doherty Institute for Infection and ImmunityWHO Collaborating Centre for Viral Hepatitis, Peter Doherty Institute for Infection and ImmunityAustralasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM)Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin UniversityNorthern Territory HealthGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin UniversityNorthern Territory HealthNorthern Territory HealthKatherine West Health BoardDepartment of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and ImmunityGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin UniversityDepartment of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and ImmunityGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin UniversityMiwatj Health Aboriginal CorporationGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin UniversityAbstract Background In the Northern Territory (NT) of Australia, First Nations people with chronic hepatitis B (CHB) are infected with a unique sub-genotype, C4, which contains mutations linked to progressive fibrosis and hepatocellular carcinoma. This cohort study aimed to investigate disease progression in C4 sub-genotype infection and estimate how many untreated individuals may benefit from antiviral therapy with broadening treatment indications. Methods Included individuals were part of Hep B PAST, a co-designed program to improve the cascade of care for people living with CHB in the NT. Disease phase and cirrhotic status were determined algorithmically using clinical and laboratory data at two time points. Loss of HBV antigens was assessed longitudinally. Treatment need was assessed cross-sectionally in the cohort at study completion. Key outcomes were estimated rates of HBsAg/HBeAg loss in sub-genotype C4 infection and quantification of how many untreated individuals qualify for therapy under current Australian and expanded global treatment guidelines. Results HBsAg and HBeAg loss occurred at a rate of 1·04 and 8·06 events/100 person-years respectively (7342·6 and 545·6 years follow up). 783 people living with CHB were included (40% female, median age 48 years). Of these, 16% had cirrhosis (an additional 6% having FibroScan > 7 kPa, meaning 22% had cirrhosis or significant fibrosis) and 25% were prescribed antivirals. Only 6·7% of untreated individuals were treatment eligible under current guidelines. Using the 2024 World Health Organisation guidelines, this increased to 50% due mostly to fibrosis and population prevalence of diabetes. Conclusions Despite advanced liver disease in people living with CHB in the NT, rates of antigen loss in sub-genotype C4 hepatitis B infection are similar to other genotypes. Further work is needed to understand drivers of cirrhosis and significant fibrosis in this population.https://doi.org/10.1186/s12879-025-11213-wChronic hepatitis BLiver cirrhosisFirst Nations healthHepatitis B virusViral genotype |
| spellingShingle | Genevieve E. Martin Kelly Hosking Kelly Banz Catherine Gargan Geoff Stewart Belinda Greenwood-Smith Penelope Ramsay Jaclyn Tate-Baker Christine Connors Paula Binks Melita McKinnon Prashanti Manchikanti George Garambaka Gurruwiwi Nicole Allard Ashleigh Qama Jessica Michaels Emily Vintour-Cesar Robert Batey Catherine Marshall Peter Nihill Tammy-Allyn Fernandes Karen Fuller Steven Y. C. Tong David Boettiger Benjamin Cowie Joshua S. Davis Sarah Mariyalawuy Bukulatjpi Jane Davies on behalf of the Hep B PAST Partnership Disease progression & treatment need in sub-genotype C4 hepatitis B infection: a retrospective cohort study in the Northern Territory, Australia BMC Infectious Diseases Chronic hepatitis B Liver cirrhosis First Nations health Hepatitis B virus Viral genotype |
| title | Disease progression & treatment need in sub-genotype C4 hepatitis B infection: a retrospective cohort study in the Northern Territory, Australia |
| title_full | Disease progression & treatment need in sub-genotype C4 hepatitis B infection: a retrospective cohort study in the Northern Territory, Australia |
| title_fullStr | Disease progression & treatment need in sub-genotype C4 hepatitis B infection: a retrospective cohort study in the Northern Territory, Australia |
| title_full_unstemmed | Disease progression & treatment need in sub-genotype C4 hepatitis B infection: a retrospective cohort study in the Northern Territory, Australia |
| title_short | Disease progression & treatment need in sub-genotype C4 hepatitis B infection: a retrospective cohort study in the Northern Territory, Australia |
| title_sort | disease progression treatment need in sub genotype c4 hepatitis b infection a retrospective cohort study in the northern territory australia |
| topic | Chronic hepatitis B Liver cirrhosis First Nations health Hepatitis B virus Viral genotype |
| url | https://doi.org/10.1186/s12879-025-11213-w |
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