Markers of HBeAg-Seroclearance in HIV-Hepatitis B Coinfection

In patients coinfected with HIV and hepatitis B virus (HBV) the kinetics of hepatitis B core-related antigen (qHBcrAg) and of anti-hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF) treatment could be used to monitor hepatitis B e-antigen (HBeAg) seroclearance. These results were published in the Journal of Infectious Diseases.

In total, 158 patients (60% HBeAg-positive and 40% HBeAg-negative) were included in a study conducted to assess the predictive ability of serum qHBcrAg, qAnti-HBc and HBV-DNA for HBeAg-seroclearance. Measures of these titers were obtained at the start of TDF and every 6 to 12 months.

Throughout a median of 4.6 years the cumulative incidence of HBsAg-seroclearance was 3.2% (n=5/518) and 27.4% (n=26/95) for HBeAg-seroclearance. The change in qHBcrAg was biphasic in patients who were HBeAg-positive (−0.051 and −0.011 log₁₀U/mL/month during <18 months and >18 months, respectively) and was monophasic in patients negative for HBeAg. The change in qAnti-HBc remained monophasic no matter the patient’s HBeAg-status.

Regarding HBeAg-seroclearance, in HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with clearance (adjusted hazard ratio [HR],  0.48/log₁₀U/mL; 95% CI, 0.33-0.70 and unadjusted HR, 1.49/log₁₀PEIU/mL; 95% CI, 1.08-2.07, respectively). At 36 months the cutoffs with the highest accuracy in predicting HBeAg-seroclearence were qHBcrAg <6.5 log₁₀U/mL at month 24 (Se=1/Sp=0.58) and baseline qAnti-HBc > 4.1 log₁₀PEIU/mL (Se=0.42/Sp=0.81).

It is important to note that the investigators only analyzed HBeAg seroclearance and not HBeAg seroconversion, which may be a more desired endpoint of treatment response. Furthermore, because so few patients achieved HBsAg seroclearance, the investigators highlight that the analysis of this endpoint was, “wholly descriptive.” Also, interpretability of HBcrAg levels observed during follow-up was somewhat difficult due to the heterogeneity of the observed levels of this marker. Finally, data on HBV genetic variability were available for patients with HBV-DNA replication, which represented a group with more active infections.

According to the investigators, serum levels of qHBcrAg and qAnti-HBc could be useful in predicting HBeAg-seroclearance in HIV/HBV coinfected patients undergoing long-term TDF. This conclusion was based on the high sensitivity of qHBcrAg and high specificity of qAnti-HBc, compared with undetectable HBV-DNA, in predicting HBeAg-seroclearance. However, their performance is not better than currently available markers and it remains debatable whether they provide further clinical utility.

Reference

Dezanet LNC, Maylin S, Gabassi A, et al. Kinetics of hepatitis B core-related antigen and anti-hepatitis B core antibody and their association with serological response in HIV-hepatitis B co-infection [published online January 21, 2020]. J Infect Dis.  doi:10.1093/infdis/jiaa013