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

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

doi:10.20411/pai.v9i2.720

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

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

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

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 log₁₀ 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; P = 0.023) but not with changes in HBV DNA (r = 0.132, P = NS). qHBsAg also correlated with ALT change (r =-0.488, P = 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.

Original language	English (US)
Pages (from-to)	43-57
Number of pages	15
Journal	Pathogens and Immunity
Volume	9
Issue number	2
DOIs	https://doi.org/10.20411/pai.v9i2.720
State	Published - Jun 18 2024

Funding

This study was supported in part by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health to the AIDS Clinical Trials Group (ACTG) under award numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701, and by NIAID grant R21 AI165171 to K.E.S. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Keywords

HBV
HBV DNA
HIV
pgRNA
quantitative HBsAg
treatment

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Molecular Biology
Microbiology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.20411/pai.v9i2.720

Cite this

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

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 log10 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; P = 0.023) but not with changes in HBV DNA (r = 0.132, P = NS). qHBsAg also correlated with ALT change (r =-0.488, P = 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.",

keywords = "HBV, HBV DNA, HIV, pgRNA, quantitative HBsAg, treatment",

author = "Sherman, {Kenneth E.} and Rouster, {Susan D.} and Heidi Meeds and Peters, {Marion G.} and Blackard, {Jason T.} and Horn, {Paul S.} and Timothy Archampong and Awewura Kwara and Mark Anderson and Michael Stec and Cloherty, {Gavin A.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors.",

year = "2024",

month = jun,

day = "18",

doi = "10.20411/pai.v9i2.720",

language = "English (US)",

volume = "9",

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journal = "Pathogens and Immunity",

issn = "2469-2964",

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T1 - Diagnostic Utility of Pre-Genomic Hepatitis B RNA in the Evaluation of HBV/HIV Coinfection

AU - Sherman, Kenneth E.

AU - Rouster, Susan D.

AU - Meeds, Heidi

AU - Peters, Marion G.

AU - Blackard, Jason T.

AU - Horn, Paul S.

AU - Archampong, Timothy

AU - Kwara, Awewura

AU - Anderson, Mark

AU - Stec, Michael

AU - Cloherty, Gavin A.

PY - 2024/6/18

Y1 - 2024/6/18

N2 - 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 log10 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; P = 0.023) but not with changes in HBV DNA (r = 0.132, P = NS). qHBsAg also correlated with ALT change (r =-0.488, P = 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.

AB - 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 log10 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; P = 0.023) but not with changes in HBV DNA (r = 0.132, P = NS). qHBsAg also correlated with ALT change (r =-0.488, P = 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.

KW - HBV

KW - HBV DNA

KW - HIV

KW - pgRNA

KW - quantitative HBsAg

KW - treatment

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VL - 9

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JO - Pathogens and Immunity

JF - Pathogens and Immunity

IS - 2

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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