Journal Article

Disease progression & treatment need in sub-genotype C4 hepatitis B infection: a retrospective cohort study in the Northern Territory, Australia

Bukulatjpi, Sarah Mariyalawuy, Davies, Jane, Ramsay, Penelope, Michaels, Jessica, Batey, Robert, Vintour-Cesar, Emily, Gargan, Catherine, McKinnon, Melita, Boettiger, David, Manchikanti, Prashanti, Tong, Steven Y. C., Allard, Nicole, Davis, Joshua S., Fernandes, Tammy-Allyn, Martin, Genevieve E., Hosking, Kelly, Tate-Baker, Jaclyn, Marshall, Catherine, Gurruwiwi, George Garambaka, Greenwood-Smith, Belinda, Fuller, Karen, Stewart, Geoff, Qama, Ashleigh, Nihill, Peter, Connors, Christine, Cowie, Benjamin, Binks, Paula, Banz, Kelly

2025

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Antigens / Antiviral agents / Antiviral Agents - therapeutic use / Australian aborigines / Chronic hepatitis B / Cirrhosis / Clinics / Cohort analysis / Cross-Sectional Studies / Development and progression / Diabetes mellitus / Disease Progression / Drug therapy / Electronic health records / Female / Fibrosis / First Nations health / Genetic aspects / Genotype / Genotype & phenotype / Genotypes / Guidelines / Health services / Hepatitis / Hepatitis B / Hepatitis B e antigen / Hepatitis B e Antigens - blood / Hepatitis B surface antigen / Hepatitis B Surface Antigens - blood / Hepatitis B virus / Hepatitis B virus - classification / Hepatitis B virus - genetics / Hepatitis B, Chronic - drug therapy / Hepatitis B, Chronic - epidemiology / Hepatitis B, Chronic - virology / Hepatocellular carcinoma / Humans / Identification and classification / Infections / Infectious Diseases / Internal Medicine / Liver cancer / Liver cirrhosis / Liver Cirrhosis - virology / Liver diseases / Male / Medical Microbiology / Medicine / Medicine & Public Health / Middle Aged / Mutation / Northern Territory - epidemiology / Parasitology / Participatory research / Retrospective Studies / Statistics / Tropical Medicine / Viral genotype / Young Adult