Hepatitis B surface antigen quantification as a predictor of seroclearance during treatment in HIV-hepatitis B virus coinfected patients from Sub-Saharan Africa

J Gastroenterol Hepatol. 2016 Mar;31(3):634-44. doi: 10.1111/jgh.13156.

Abstract

Background and aim: In Sub-Saharan Africa, seroclearance of hepatitis B surface antigen (HBsAg) and hepatitis B "e" antigen (HBeAg), including their quantifiable markers, have rarely been evaluated during long-term antiviral treatment among patients coinfected with HIV and hepatitis B virus (HBV).

Methods: In this prospective cohort study from two randomized-control trials in Côte d'Ivoire, 161 antiretroviral-naïve HIV-HBV coinfected patients starting lamivudine (n = 76) or tenofovir/emtricitabine (n = 85) containing antiretroviral therapy were included. HBV DNA was quantified using an in-house assay (detection limit = 12 copies/mL) and HBsAg quantification (qHBsAg) using the Elecsys assay.

Results: Overall, 33 (20.5%) patients were HBeAg positive, 121 (75.2%) had detectable HBV DNA, and 92/93 (98.9%) harbored HBV genotype E. Median treatment duration was 35.5 months (interquartile range: 24.3-36.4). Among HBeAg-positive patients, cumulative proportion with HBeAg seroclearance was 46.3% (n = 14). Overall, cumulative proportion of HBsAg seroclearance was 6.6% (n = 10). Lower baseline qHBsAg levels and strong 12-month declines in qHBsAg were significantly associated with HBsAg seroclearance for both HBeAg-negative and HBeAg-positive patients. When taken at certain levels, these determinants provided moderate sensitivity (Se) and specificity (Sp) in predicting HBsAg seroclearance at month 36 (≤ 1000 IU/mL at baseline, Se = 0.80, Sp = 0.80; ≥ 1.0 log10 IU/mL drop at month 12, Se = 0.57, Sp = 1.00). Instead, qHBsAg levels ≤ 100 or ≤ 10 IU/mL at month 12 were optimal (both Se = 0.90 and Sp = 1.00). Detectable HBV-DNA provided fairly high Se and Sp when evaluated at baseline (Se = 1.00, Sp = 0.80), but not at month 12 (Se = 0.80, Sp = 0.40).

Conclusions: HBsAg seroclearance rates are not common in patients from Sub-Saharan Africa treated with anti-HBV containing antiretroviral therapy. qHBsAg levels at 12 months of treatment may accurately predict HBsAg seroclearance.

Keywords: HBeAg quantification; HBsAg quantification; chronic viral hepatitis; immunosuppression; serological endpoints.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa
  • Antiviral Agents / administration & dosage
  • Biomarkers / blood
  • Cohort Studies
  • Coinfection / diagnosis
  • Coinfection / drug therapy*
  • Coinfection / virology*
  • Drug Therapy, Combination
  • Emtricitabine / administration & dosage
  • HIV Infections / diagnosis
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • Hepatitis B / diagnosis
  • Hepatitis B / drug therapy*
  • Hepatitis B / virology*
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B e Antigens / blood
  • Humans
  • Lamivudine / administration & dosage
  • Predictive Value of Tests
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Sensitivity and Specificity
  • Tenofovir / administration & dosage
  • Time Factors

Substances

  • Antiviral Agents
  • Biomarkers
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Lamivudine
  • Tenofovir
  • Emtricitabine