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

• Published in: Alimentary pharmacology & therapeutics Vol. 57; no. 5; pp. 509 - 523
• Main Authors: Wagner, Josef, Yuen, Lilly, Littlejohn, Margaret, Sozzi, Vitina, Jackson, Kathy, Martin, Ross, Aeschbacher, Thomas, Suri, Vithika, Tan, Susanna K., Feierbach, Becket, Gaggar, Anuj, Marcellin, Patrick, Buti Ferret, Maria, Janssen, Harry L. A., Gane, Ed, Meagher, Niamh, Price, David J., Wong, Darren, Thompson, Alexander T., Revill, Peter A.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2023
• Subjects: Antiviral agents; Antiviral Agents - therapeutic use; Biomarkers; DNA, Viral - analysis; DNA, Viral - genetics; Genomes; Genotype; Genotypes; Haplotypes; Hepatitis B; Hepatitis B e antigen; Hepatitis B e Antigens - genetics; Hepatitis B surface antigen; Hepatitis B Surface Antigens - genetics; Hepatitis B virus - genetics; Hepatitis B, Chronic - diagnosis; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - genetics; Hepatitis C, Chronic - drug therapy; Humans; Interferon; Tenofovir; Tenofovir - therapeutic use
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.17299

Summary 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. Hepatitis B virus (HBV) haplotype number ≤2 predicts HBV genotype A and D patients who will, or will not achieve HBsAg loss on direct acting antiviral therapy