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. 2023 Feb 1;77(2):594-605.
doi: 10.1002/hep.32634. Epub 2022 Jul 21.

HBV transcription and translation persist despite viral suppression in HBV-HIV co-infected patients on antiretroviral therapy

Mauricio Lisker-Melman  1 , Abdus S Wahed  2 , Marc G Ghany  3 , Raymond T Chung  4 , Wendy C King  5 , David E Kleiner  6 , Atul K Bhan  7 , Mandana Khalili  8 , Mamta K Jain  9 , Mark Sulkowski  10 , David K Wong  11 , Gavin Cloherty  12 , Richard K Sterling  13
Affiliations

HBV transcription and translation persist despite viral suppression in HBV-HIV co-infected patients on antiretroviral therapy

Mauricio Lisker-Melman et al. Hepatology. .

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.

Trial registration: ClinicalTrials.gov NCT01924455.

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Conflict of interest statement

CONFLICT OF INTEREST

Gavin Cloherty owns stock and is employed by Abbott. Mamta K. Jain received grants from Gilead, Merck, and Janssen. Mauricio Lisker-Melman is on the speakers’ bureau for AbbVie and Gilead. Mandana Khalili consults for and received grants from Gilead. She received grants from Intercept. Mark Sulkowski consults for Gilead and Antios. He consults for and received grants from Assembly Biosciences. Raymond T. Chung owns stock in Gilead, BMS, Janssen, AbbVie, Roche, and GSK. Richard K. Sterling received grants from Abbott, Roche, AbbVie, and Gilead. He is on the DSMB for Pfizer and AskBio. Abdus S. Wahed consults for Merck. Wendy C. King received grants from AbbVie.

Figures

FIGURE 1
FIGURE 1
Ishak and histological activity index scores by HBcAg immunohistochemistry (IHC) grade.
FIGURE 2
FIGURE 2
Ishak and histological activity index scores by HBsAg IHC grade.
FIGURE 3
FIGURE 3
HBV RNA and hepatitis B core antigen (HBcrAg) by HBcAg IHC and HBsAg IHC grades. Top left: HBV RNA by HBcAg IHC grade. Top right: HBV RNA by HBsAg IHC grade. Bottom left: HBcrAg by HBcAg IHC grade. Bottom right: HBcrAg by HBsAg IHC grade.
See this image and copyright information in PMC

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