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Abstract Details
Hepatitis B virus haplotype number at baseline is a predictive marker of functional cure during antiviral therapy for patients with genotypes A and D HBeAg-positive chronic hepatitis B
Aliment Pharmacol Ther. 2022 Nov 25. doi: 10.1111/apt.17299. Online ahead of print.
1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
2Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
3Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
4Gilead Sciences, Foster City, California, USA.
5Hôpital Beaujon, University of Paris, Clichy, France.
6Liver Unit, Valle d'Hebron (Ciberehd) University Hospital, Barcelona, Spain.
7Toronto Center for Liver Diseases, Toronto General Hospital, University: Health Network, University of Toronto, Toronto, Ontario, Canada.
8New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand.
9Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
10Department of Gastroenterology, St. Vincent's Hospital, Melbourne, Victoria, Australia.
11Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Abstract
Backgrounds and aims: We investigated associations between hepatitis B virus (HBV) genome-length haplotype number (HN) at baseline in subjects with HBeAg-positive chronic hepatitis B (CHB), and the likelihood of achieving functional cure during direct-acting antiviral therapy METHOD: We analysed 86 HBeAg-positive baseline samples from patients with HBV genotypes A and D who were enrolled in a Phase II trial of tenofovir disoproxil fumarate (TDF) to determine if HN was a biomarker of HBsAg loss during therapy. Findings were validated using baseline samples from 181 patients with HBV genotypes A and D from an independent clinical trial utilising TDF or tenofovir alafenamide therapy in HBeAg-positive CHB.
Results: In the HBeAg-positive test cohort, patients with genotypes A or D and ≤2 haplotypes had a minimum of 21-fold higher likelihood of achieving HBsAg loss on TDF. Baseline HN (p < 0.0001) was a stronger predictor of HBsAg loss on therapy than HBsAg titre (p = 0.03), HBeAg titre (p = 0.0002), or the presence of HBV basal core promoter (A1762T, p = 0.0379 and G1764A, p = 0.0176) or G1896A precore mutations (p = 0.0218). This finding was validated in the independent validation cohort. HN was statistically higher in patients with HBV genotypes B or C infection compared to genotypes A and D.
Conclusion: Baseline HN ≤2 predicts which patients with HBV genotypes A or D will more likely progress to functional cure on current direct-acting antiviral therapy, with greater accuracy than current biomarkers including baseline HBsAg and HBeAg titre.