1. HBV transcription and translation persist despite viral suppression in HBV-HIV co-infected patients on antiretroviral therapy.
- Author
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Lisker-Melman M, Wahed AS, Ghany MG, Chung RT, King WC, Kleiner DE, Bhan AK, Khalili M, Jain MK, Sulkowski M, Wong DK, Cloherty G, and Sterling RK
- Subjects
- Adult, Humans, Male, Middle Aged, Biomarkers, Cross-Sectional Studies, DNA, Viral, Hepatitis B Core Antigens, Hepatitis B e Antigens, Hepatitis B Surface Antigens, RNA, Protein Biosynthesis drug effects, Coinfection drug therapy, Coinfection immunology, Coinfection physiopathology, Coinfection virology, Hepatitis B virus drug effects, Hepatitis B virus immunology, Hepatitis B, Chronic complications, Hepatitis B, Chronic drug therapy, Hepatitis B, Chronic immunology, Hepatitis B, Chronic virology, HIV Infections complications, HIV Infections drug therapy, HIV Infections immunology, Viral Transcription drug effects, Anti-Retroviral Agents pharmacology, Anti-Retroviral Agents therapeutic use
- Abstract
Background and Aims: Liver injury may persist in patients with HBV receiving antiviral therapy who have ongoing transcription and translation. We sought to assess ongoing HBV transcription by serum HBV RNA, translation by serum hepatitis B core related antigen (HBcrAg), and their associations with hepatic HBsAg and HBcAg staining in patients coinfected with HBV and HIV., Methods: This is a cross-sectional study of 110 adults coinfected with HBV and HIV who underwent clinical assessment and liver biopsy. Immunohistochemistry (IHC) was performed for HBsAg and HBcAg. Viral biomarkers included quantitative HBsAg, HBV RNA, and HBcrAg., Results: Participants' median age was 49 years (male, 93%; Black, 51%; HBeAg+, 65%), with suppressed HBV DNA (79%) and undetectable HIV RNA (77%) on dually active antiretroviral therapy. Overall, HBV RNA and HBcrAg were quantifiable in 81% and 83%, respectively (96% and 100% in HBeAg+, respectively). HBcAg staining was detected in 60% and HBsAg in 79%. Higher HBV RNA was associated with higher HBcAg and HBsAg IHC grades (both p < 0.0001). The HBsAg membranous staining pattern was significantly associated with higher HBV-RNA and HBcrAg levels., Conclusion: HBcAg and HBsAg IHC staining persisted despite viral suppression, and IHC grades and staining patterns correlated with markers of transcription (HBV RNA) and translation (HBcrAg). These data indicate that apparent HBV suppression is associated with residual transcription and translation that could contribute to liver pathology. Additional antiviral strategies directed to HBV protein expression may be useful to ameliorate liver injury., (Copyright © 2023 American Association for the Study of Liver Diseases.)
- Published
- 2023
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