Diagnostic Utility of Pre-Genomic Hepatitis B RNA in the Evaluation of HBV/HIV Coinfection

Overview

Journal Pathog Immun

Date 2024 Aug 13

PMID 39135958

Authors

Kenneth E Sherman

Susan D Rouster

Heidi Meeds

Marion G Peters

Jason T Blackard

Paul S Horn

Timothy Archampong

Awewura Kwara

Mark Anderson

Michael Stec

Gavin A Cloherty

Affiliations

Soon will be listed here.

Abstract

Background: Newer biomarkers of Hepatitis B virus (HBV) infection and treatment response have not been well-characterized in individuals with HBV/HIV coinfection.

Methods: Pre-genomic RNA (pgRNA) and quantitative HBsAg (qHBsAg) were used to evaluate the associations with baseline characteristics. Participants included two separate groups - 236 with HBV/HIV coinfection enrolled in a cross-sectional cohort in Ghana and 47 from an HBV nucleoside/nucleotide treatment trial comparing tenofovir to adefovir in the United States.

Results: In both cohorts, HBe antigenemia was highly associated with pgRNA and HBV DNA levels. In the treatment cohort, pre-treatment pgRNA serum concentration was 7.0 log U/mL, and mean qHBsAg was 201,297 IU/mL. The observed treatment-associated decrease in pgRNA was consistent with a biphasic decline curve that reached second-phase kinetics following treatment week 12. Changes from baseline were significantly correlated with changes in serum ALT (r = - 0.518; = 0.023) but not with changes in HBV DNA (r = 0.132, = NS). qHBsAg also correlated with ALT change (r = - 0.488, = 0.034).

Conclusion: pgRNA and qHBsAg represent newer biomarkers of HBV replication that may help monitor response and treatment outcomes. HBV pgRNA is highly associated with both HBeAg and ALT and may predict both active replication from the closed circular DNA (cccDNA) template as well as hepatic injury.

References

Peters M, Andersen J, Lynch P, Liu T, Alston-Smith B, Brosgart C . Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127. Hepatology. 2006; 44(5):1110-6. PMC: 4114764. DOI: 10.1002/hep.21388. View

Lisker-Melman M, Wahed A, Ghany M, Chung R, King W, Kleiner D . HBV transcription and translation persist despite viral suppression in HBV-HIV co-infected patients on antiretroviral therapy. Hepatology. 2022; 77(2):594-605. PMC: 9800637. DOI: 10.1002/hep.32634. View

Patel E, Thio C, Boon D, Thomas D, Tobian A . Prevalence of Hepatitis B and Hepatitis D Virus Infections in the United States, 2011-2016. Clin Infect Dis. 2019; 69(4):709-712. PMC: 6669285. DOI: 10.1093/cid/ciz001. View

Zoutendijk R, Zaaijer H, de Vries-Sluijs T, Reijnders J, Mulder J, Kroon F . Hepatitis B surface antigen declines and clearance during long-term tenofovir therapy in patients coinfected with HBV and HIV. J Infect Dis. 2012; 206(6):974-80. DOI: 10.1093/infdis/jis439. View

Pan J, Tian Y, Xu J, Luo H, Tan N, Han Y . Dynamics of Hepatitis B Virus Pregenomic RNA in Chronic Hepatitis B Patients With Antiviral Therapy Over 9 Years. Front Med (Lausanne). 2022; 9:851717. PMC: 9099358. DOI: 10.3389/fmed.2022.851717. View

Gao M, Feng C, Ying R, Nie Y, Deng X, Zhu Y . A novel one-step quantitative reverse transcription PCR assay for selective amplification of hepatitis B virus pregenomic RNA from a mixture of HBV DNA and RNA in serum. Arch Virol. 2019; 164(11):2683-2690. DOI: 10.1007/s00705-019-04372-0. View

Xu L, Li X, Lu L, Liu X, Song X, Li Y . HBV pgRNA profiles in Chinese HIV/HBV coinfected patients under pre- and posttreatment: a multicentre observational cohort study. J Viral Hepat. 2022; 29(8):616-626. PMC: 9541493. DOI: 10.1111/jvh.13704. View

Grudda T, Hwang H, Taddese M, Quinn J, Sulkowski M, Sterling R . Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment. J Clin Invest. 2022; 132(18). PMC: 9473722. DOI: 10.1172/JCI161818. View

Anderson M, Stec M, Thi E, Picchio G, Mbanya D, Cloherty G . Measuring hepatitis B pgRNA stability using an updated automated HBV pgRNA assay with increased sensitivity. Hepatol Commun. 2023; 7(4). PMC: 10027030. DOI: 10.1097/HC9.0000000000000099. View

10.

Lin N, Ye A, Lin J, Liu C, Huang J, Fu Y . Diagnostic Value of Detection of Pregenomic RNA in Sera of Hepatitis B Virus-Infected Patients with Different Clinical Outcomes. J Clin Microbiol. 2019; 58(2). PMC: 6989074. DOI: 10.1128/JCM.01275-19. View

11.

Yip T, Lok A . How Do We Determine Whether a Functional Cure for HBV Infection Has Been Achieved?. Clin Gastroenterol Hepatol. 2019; 18(3):548-550. DOI: 10.1016/j.cgh.2019.08.033. View

12.

Kim S, Yoon J, Lee M, Cho Y . Toward a complete cure for chronic hepatitis B: Novel therapeutic targets for hepatitis B virus. Clin Mol Hepatol. 2021; 28(1):17-30. PMC: 8755466. DOI: 10.3350/cmh.2021.0093. View

13.

Strassl R, Reiberger T, Honsig C, Payer B, Mandorfer M, Grabmeier-Pfistershammer K . Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance in HIV-/HBV-coinfected patients. J Viral Hepat. 2013; 21(7):508-16. DOI: 10.1111/jvh.12175. View

14.

Rattanachaisit P, Suksawatamnuay S, Sriphoosanaphan S, Thanapirom K, Thaimai P, Siripon N . Stability of hepatitis B virus pregenomic RNA in plasma specimens under various temperatures and storage conditions. PeerJ. 2021; 9:e11207. PMC: 8052958. DOI: 10.7717/peerj.11207. View

15.

Sherman K . Management of the Hepatitis B Virus/HIV-Coinfected Patient. Top Antivir Med. 2015; 23(3):111-4. PMC: 6148934. View

16.

Jeng W, Lok A . What will it take to cure hepatitis B?. Hepatol Commun. 2023; 7(4). PMC: 10043561. DOI: 10.1097/HC9.0000000000000084. View

17.

Jakharia N, Kottilil S, Chua J . Quantification of Hepatitis B Surface Antigen: Is there a Role in HIV-Hepatitis B Virus Coinfection?. AIDS Rev. 2019; 21(4):175-183. DOI: 10.24875/AIDSRev.19000077. View

18.

Boyd A, Gozlan J, Miailhes P, Lascoux-Combe C, Cam M, Rougier H . Rates and determinants of hepatitis B 'e' antigen and hepatitis B surface antigen seroclearance during long-term follow-up of patients coinfected with HIV and hepatitis B virus. AIDS. 2015; 29(15):1963-73. DOI: 10.1097/QAD.0000000000000795. View

19.

Ligat G, Verrier E, Nassal M, Baumert T . Hepatitis B virus-host interactions and novel targets for viral cure. Curr Opin Virol. 2021; 49:41-51. PMC: 7613419. DOI: 10.1016/j.coviro.2021.04.009. View

20.

Matthews G, Ali R, Avihingsanon A, Amin J, Hammond R, Bowden S . Quantitative HBsAg and HBeAg predict hepatitis B seroconversion after initiation of HAART in HIV-HBV coinfected individuals. PLoS One. 2013; 8(4):e61297. PMC: 3622017. DOI: 10.1371/journal.pone.0061297. View