The kinetics of the hepatitis B surface antigen level after the initiation of antiretroviral therapy for hepatitis B virus and human immunodeficiency virus coinfected patients

Abstract Background The aim of the current study was to describe the kinetics of quantified hepatitis B core–related antigen (qHBcrAg) and quantified anti–hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF) treatment and assess their ability to predict hepatitis B e antigen (HBeAg) seroclearance in patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus. Methods Serum qHBcrAg, qAnti-HBc, and hepatitis B virus DNA were obtained at TDF initiation and every 6–12 months. The on-treatment kinetics of qHBcrAg (ΔqHBcrAg) and qAnti-HBc (ΔqAnti-HBc) were estimated using mixed-effect linear regression. Hazard ratios (HRs) assessing the association between markers and HBeAg seroclearance were calculated using proportional hazards regression, and the sensitivity (Se) and specificity (Sp) of marker levels in predicting HBeAg seroclearance were assessed using time-dependent receiving operating characteristic curves. Results During a median of 4.6 years, the cumulative incidences of hepatitis B surface antigen and HBeAg seroclearance were 3.2% (n = 5 of 158) and 27.4% (n = 26 of 95), respectively. ΔqHBcrAg was biphasic in HBeAg-positive patients (−0.051 and −0.011 log10 U/mL/mo during ≤18 and >18 months, respectively) and monophasic in HBeAg-negative patients. ΔqAnti-HBc was monophasic regardless of HBeAg status. In HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with HBeAg seroclearance (adjusted HR, 0.48/log10 U/mL [95% confidence interval, .33–.70] and unadjusted HR, 1.49/log10 Paul Ehrlich Institute units/mL [1.08–2.07], respectively). Cutoffs with the highest accuracy in predicting HBeAg seroclearance at 36 months were qHBcrAg <6.5 log10 U/mL at month 24 (Se, 1; Sp, 0.58) and baseline qAnti-HBc ≥4.1 log10 Paul Ehrlich Institute units/mL (Se, 0.42; Sp, 0.81). Conclusions In coinfected patients undergoing TDF, qHBcrAg/qAnti-HBc could be of use in monitoring HBeAg seroclearance.

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High Rates of Hepatitis B Virus (HBV) Functional Cure Among Human Immunodeficiency Virus-HBV Coinfected Patients on Antiretroviral Therapy in Zambia

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz450 ◽

2019 ◽

Vol 221 (2) ◽

pp. 218-222 ◽

Cited By ~ 3

Author(s):

Belinda V Chihota ◽

Gilles Wandeler ◽

Roma Chilengi ◽

Lloyd Mulenga ◽

Raymond T Chung ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis B Virus ◽

Antiretroviral Therapy ◽

Hepatitis B ◽

Hepatitis B Surface Antigen ◽

Multivariable Analysis ◽

Cd4 Count ◽

Functional Cure ◽

B Virus ◽

Immunodeficiency Virus

Abstract Among 284 human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected adults starting tenofovir-based antiretroviral therapy (ART) in Zambia, median baseline CD4+ count was 202 cells/mm3 and 41.6% were hepatitis B e-antigen positive. Within 2 years of therapy, 29 (10.2%) participants experienced HBV functional cure (confirmed loss of hepatitis B surface antigen). In multivariable analysis, baseline CD4 count <350 cells/mm3, female sex, and lower baseline HBV deoxyribonucleic acid were associated with increased odds of functional cure. Immune recovery during HIV-HBV treatment with ART may drive higher rates of functional cure than during HBV monoinfection treatment. Understanding the mechanisms underlying this phenomenon could inform immunomodulatory therapies for HBV cure.

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Cytokines and Chemokines Involved in Hepatitis B Surface Antigen Loss in Human Immunodeficiency Virus/Hepatitis B Virus Coinfected Patients

Journal of Clinical Medicine ◽

10.3390/jcm10040833 ◽

2021 ◽

Vol 10 (4) ◽

pp. 833

Author(s):

Noboru Urata ◽

Tsunamasa Watanabe ◽

Noboru Hirashima ◽

Yoshiyuki Yokomaku ◽

Junji Imamura ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Gm Csf ◽

Cytokines And Chemokines ◽

Hbsag Clearance ◽

B Virus ◽

Immunodeficiency Virus

It has been reported that hepatic flare (HF), attributable to the development of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfected patients, occurs frequently after the start of anti-retroviral therapy (ART). We have observed several cases of hepatitis B surface antigen (HBsAg) loss after IRIS. However, the factors leading to HBsAg clearance remain unknown. We measured CD4+ and CD8+ T cells, cytokines and chemokines in 16 patients coinfected HIV-1 and HBV with IRIS, and analyzed the factors leading to HBsAg clearance after IRIS. There was no significant difference in the CD4+ and CD8+ T cell counts between the HBsAg clearance and non-clearance groups, while the serum concentrations of almost all cytokines and chemokines in the HBsAg clearance group were higher than in the HBsAg non-clearance group at any time of observation. In particular, IP-10 at the ALT peak, GM-CSF and IL-12 one month after the ALT peak and TNF-α and GM-CSF after the ALT concentrations fell to within normal limits, were significantly higher in the HBsAg clearance group. It seems that HBsAg loss after IRIS requires continued immune responses against HBV, involving Th1 cytokines.

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Routine hepatitis B virus DNA testing in human immunodeficiency virus-infected patients with positive hepatitis B core antibody but negative hepatitis B surface antigen is not justified by current evidence

Hepatology ◽

10.1002/hep.23395 ◽

2010 ◽

Vol 51 (3) ◽

pp. 1087-1088 ◽

Cited By ~ 2

Author(s):

Marina Núñez

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Current Evidence ◽

Dna Testing ◽

Hepatitis B Virus Dna ◽

B Virus ◽

Immunodeficiency Virus

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Oral Adenoviruses as the Carriers for Human Immunodeficiency Virus or Hepatitis B Virus Surface Antigen Genes

Biotechnology and Pharmacy ◽

10.1007/978-94-015-8135-6_11 ◽

1993 ◽

pp. 275-289

Author(s):

Michael D. Lubeck ◽

Satoshi Mizutani ◽

Alan R. Davis ◽

Paul P. Hung

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Surface Antigen ◽

Virus Surface ◽

Virus Surface Antigen ◽

B Virus ◽

Immunodeficiency Virus

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Association of Hepatitis B Core-Related Antigen and Antihepatitis B Core Antibody With Liver Fibrosis Evolution in Human Immunodeficiency Virus-Hepatitis B Virus Coinfected Patients During Treatment With Tenofovir

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa215 ◽

2020 ◽

Vol 7 (7) ◽

Author(s):

Romuald Cruchet ◽

Lorenza N C Dezanet ◽

Sarah Maylin ◽

Audrey Gabassi ◽

Hayette Rougier ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis B Virus ◽

Antiretroviral Therapy ◽

Liver Fibrosis ◽

Hepatitis B ◽

Advanced Fibrosis ◽

B Virus ◽

Immunodeficiency Virus ◽

Fibrosis Regression

Abstract Background Quantitative hepatitis B core-related antigen (qHBcrAg) or antihepatitis B core antibody (qAnti-HBc) could be useful in monitoring liver fibrosis evolution during chronic hepatitis B virus (HBV) infection, yet it has not been assessed in human immunodeficiency virus (HIV)-HBV-coinfected patients undergoing treatment with tenofovir (TDF). Methods One hundred fifty-four HIV-HBV-infected patients initiating a TDF-containing antiretroviral regimen were prospectively followed. The qHBcrAg and qAnti-HBc and liver fibrosis assessment were collected every 6–12 months during TDF. Hazard ratios (HRs) assessing the association between qHBcrAg/qAnti-HBc and transitions from none/mild/significant fibrosis to advanced fibrosis/cirrhosis (progression) and from advanced fibrosis/cirrhosis to none/mild/significant fibrosis (regression) were estimated using a time-homogeneous Markov model. Results At baseline, advanced liver fibrosis/cirrhosis was observed in 40 (26%) patients. During a median follow-up of 48 months (interquartile range, 31–90), 38 transitions of progression (IR = 7/100 person-years) and 34 transitions of regression (IR = 6/100 person-years) were observed. Baseline levels of qHBcrAg and qAnti-HBc were not associated with liver fibrosis progression (adjusted-HR per log10 U/mL = 1.07, 95% confidence interval [CI] = 0.93–1.24; adjusted-HR per log10 Paul-Ehrlich-Institute [PEI] U/mL = 0.85, 95% CI = 0.70–1.04, respectively) or regression (adjusted-HR per log10 U/mL = 1.17, 95% CI = 0.95–1.46; adjusted-HR per log10 PEI U/mL = 0.97, 95% CI = 0.78–1.22, respectively) after adjusting for age, gender, duration of antiretroviral therapy, protease inhibitor-containing antiretroviral therapy, and CD4+/CD8+ ratio. Nevertheless, changes from the previous visit of qAnti-HBc levels were associated with liver fibrosis regression (adjusted-HR per log10 PEIU/mL change = 5.46, 95% CI = 1.56–19.16). Conclusions Baseline qHBcrAg and qAnti-HBc levels are not associated with liver fibrosis evolution in TDF-treated HIV-HBV coinfected patients. The link between changes in qAnti-HBc levels during follow-up and liver fibrosis regression merits further study.

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