Analysis of Viral Variants and Biomarkers in Hepatitis B Virus (HBV) and Hepatitis Delta Virus (HDV) Coinfected Individuals
Date
2024-07-02
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Abstract
Hepatitis B virus (HBV) and hepatitis Delta virus (HDV) coinfection can cause the most severe form of viral hepatitis in humans. The HDV needs HBV to disseminate, co-opting HBV surface antigen (HBsAg) during assembly. Both viruses have error-prone replication leading to increased variability. We aim to compare clinical and viral outcomes in a contemporary cohort of HBV/HDV coinfected (HBsAg positive and HDV antibody (anti-HDV) positive) vs. HBV monoinfected (HBsAg positive, anti-HDV negative) individuals. Viral variants, HBV biomarkers, HBV DNA, and quantitative HBV surface antigen (qHBsAg) were assessed. Nucleic acid related antigen (NRAg) and HBV core antibody (qAHBc) were quantified by ELISA. HDV RNA/HBV DNA was tested by qPCR. HBV S, X, and HDV delta gene were analyzed by Sanger and Next Generation Sequencing (NGS) and MEGAX. In this prospective study, 25 anti-HDV+/HBsAg+ patients (median age 41y (SD10), 10 females, mostly Asian (n=10) and HBeAg negative (n=19), with median 5 years follow-up (range 1-10). The known HBV genotypes (GT) (n=16) were 3A, 10D, 3E, and known HDV GT (n=19) were 1 (n=16), 2 (n=1), 5 (n=2). Data was compared to a contemporary cohort of 20 HBV monoinfected patients (median age 45y (SD10), 7F, mostly Asian (n=15), with HBV GT 2A, 3B, 12C, 2D, 1E, all HBeAg (-). Single nucleotide polymorphism (SNP) analysis of the HBV S to date in 11/20 by Sanger sequencing showed no mutations, but 3/20 showed X gene variants. Similarly, HBV X NGS analysis in 2 patients showed 16 mutations and 18 S variants in 9 patients. NGS analysis of S gene showed 6 unique mutations not found in the HBV/HDV coinfected cohort. In 25 HBsAg+/anti-HDV+ patients, 19 are HBeAg(-), with low-level HBV viremia, high qHBsAg, and 23/25 HDV RNA+. NGS and SNP analysis showed unique HBV S/X variants. The X and/or S mutations detected correlate with severe liver disease, impaired replication, HCC development, decreased antigenicity and vaccine escape. We found unique SNPs/variants and increased diversity over time in the HDV gene. In summary, this study provides novel data on HBV and/or HDV viral sequence changes in a cohort with high risk of liver disease progression over long-term follow-up.
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Keywords
Hepatitis B Virus, Hepatitis Delta Virus, HBV Variants, NGS, Hepatitis B and D Virus Coinfection
Citation
Presbitero, A. (2024). Analysis of viral variants and biomarkers in hepatitis B virus (HBV) and hepatitis delta virus (HDV) coinfected individuals (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.