TY - JOUR
T1 - Correlation of serum hepatitis B core-related antigen with hepatitis B virus total intrahepatic DNA and covalently closed circular-DNA viral load in HIV–hepatitis B coinfection
AU - Dezanet, Lorenza N.C.
AU - Maylin, Sarah
AU - Gabassi, Audrey
AU - Rougier, Hayette
AU - Miailhes, Patrick
AU - Lascoux-Combe, Caroline
AU - Chas, Julie
AU - Girard, Pierre Marie
AU - Delaugerre, Constance
AU - Zoulim, Fabien
AU - Lacombe, Karine
AU - Boyd, Anders
N1 - Funding Information: Source of funding: The current work was supported by SIDACTION (AO 19) and the ANRS. Gilead Sciences, Inc. provided an unrestricted grant for the French HIV– HBV cohort and was not involved in any part of the data collection, analysis, and article writing. Funding Information: The current study was sponsored by the Institut de Médecine et d’Epidémiologie Appliquée (IMEA). L.N.C.D. was awarded a postdoctoral fellowship from the France REcherche Nord&sud Sida-hiv Hépatites (ANRS). Funding Information: The current work was supported by SIDACTION (AO 19) and the ANRS. Gilead Sciences, Inc. provided an unrestricted grant for the French HIV?HBV cohort and was not involved in any part of the data collection, analysis, and article writing. Publisher Copyright: Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Objective: To assess whether quantified hepatitis B core-related antigen (qHBcrAg) is a surrogate marker of intrahepatic replication in HIV and hepatitis B virus (HBV) coinfection. Design: Cross-sectional study of 31 HIV – HBV-infected patients (total liver biopsies, n ¼ 38) from a well defined cohort. Methods: Spearman’s rank correlation coefficients were calculated between qHBcrAg and intrahepatic markers of HBV replication [total intrahepatic-DNA, covalently closed circular (ccc) DNA, cccDNA: total intrahepatic-DNA ratio]. Results: At biopsy, 22 (71.0%) patients were hepatitis B ‘e’ antigen (HBeAg)-positive, 22 (71.0%) had detectable plasma HBV-DNA, and 17 (54.8%) were treated with tenofovir. Median levels (interquartile range) of intrahepatic markers were as follows: HBV cccDNA (n ¼ 34), 0.26 copies/cell (0.4 – 2.89); total intrahepatic-DNA (n ¼ 38), 2.38 copies/cell (0.58 – 207.9), and cccDNA: total intrahepatic-DNA ratio (n ¼ 34), 0.05 (interquartile range ¼ 0.01 – 0.12). There was a significantly strong correlation between qHBcrAg and cccDNA in all patients (Rho ¼ 0.65, P < 0.001), while a moderate correlation was observed between qHBcrAg and total intrahepatic-DNA (Rho ¼ 0.57, P < 0.001) or cccDNA: total intrahepatic-DNA ratio (Rho ¼ -0.45, P ¼ 0.01). Similar findings were observed for HBeAg-positive patients and those with detectable HBV-DNA, with the exception of qHBcrAg and cccDNA or cccDNA: total intrahepatic-DNA ratio. In contrast, no significant correlation between qHBcrAg and any intrahepatic marker was observed in HBeAg-negative patients or those with undetectable HBV-DNA. No significant difference was observed in median qHBcrAg levels across liver fibrosis stages (P ¼ 0.5). Conclusion: qHBcrAg is a potential surrogate marker of cccDNA in HIV–HBV coinfected patients, yet might be less useful with undetectable serum HBV-DNA or HBeAg-negative status. Whether qHBcrAg provides further clinical utility compared with other serological markers remains debatable.
AB - Objective: To assess whether quantified hepatitis B core-related antigen (qHBcrAg) is a surrogate marker of intrahepatic replication in HIV and hepatitis B virus (HBV) coinfection. Design: Cross-sectional study of 31 HIV – HBV-infected patients (total liver biopsies, n ¼ 38) from a well defined cohort. Methods: Spearman’s rank correlation coefficients were calculated between qHBcrAg and intrahepatic markers of HBV replication [total intrahepatic-DNA, covalently closed circular (ccc) DNA, cccDNA: total intrahepatic-DNA ratio]. Results: At biopsy, 22 (71.0%) patients were hepatitis B ‘e’ antigen (HBeAg)-positive, 22 (71.0%) had detectable plasma HBV-DNA, and 17 (54.8%) were treated with tenofovir. Median levels (interquartile range) of intrahepatic markers were as follows: HBV cccDNA (n ¼ 34), 0.26 copies/cell (0.4 – 2.89); total intrahepatic-DNA (n ¼ 38), 2.38 copies/cell (0.58 – 207.9), and cccDNA: total intrahepatic-DNA ratio (n ¼ 34), 0.05 (interquartile range ¼ 0.01 – 0.12). There was a significantly strong correlation between qHBcrAg and cccDNA in all patients (Rho ¼ 0.65, P < 0.001), while a moderate correlation was observed between qHBcrAg and total intrahepatic-DNA (Rho ¼ 0.57, P < 0.001) or cccDNA: total intrahepatic-DNA ratio (Rho ¼ -0.45, P ¼ 0.01). Similar findings were observed for HBeAg-positive patients and those with detectable HBV-DNA, with the exception of qHBcrAg and cccDNA or cccDNA: total intrahepatic-DNA ratio. In contrast, no significant correlation between qHBcrAg and any intrahepatic marker was observed in HBeAg-negative patients or those with undetectable HBV-DNA. No significant difference was observed in median qHBcrAg levels across liver fibrosis stages (P ¼ 0.5). Conclusion: qHBcrAg is a potential surrogate marker of cccDNA in HIV–HBV coinfected patients, yet might be less useful with undetectable serum HBV-DNA or HBeAg-negative status. Whether qHBcrAg provides further clinical utility compared with other serological markers remains debatable.
KW - Biomarker
KW - Covalently closed circular DNA
KW - HIV
KW - Hepatitis B core-related antigen
KW - Hepatitis B virus
KW - Intrahepatic DNA
UR - http://www.scopus.com/inward/record.url?scp=85092680788&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/QAD.0000000000002659
DO - https://doi.org/10.1097/QAD.0000000000002659
M3 - Article
C2 - 32773480
SN - 0269-9370
VL - 34
SP - 1943
EP - 1949
JO - AIDS
JF - AIDS
IS - 13
ER -