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

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