Serum Hepatitis B Virus RNA Levels Predict HBeAg Seroconversion and Virological Response in Chronic Hepatitis B Patients with High Viral Load Treated with Nucleos(t)ide Analog

Abstract

Background and Aim

Hepatitis B virus (HBV) RNA has attracted increasing attention as a novel serum marker for intrahepatic HBV replication. However, the predictive value of the serum level of HBV RNA for hepatitis B e-antigen (HBeAg) seroconversion and viral response among patients with a high viral load (HVL) is unclear. We evaluated the role of the serum level of HBV RNA as a predictor of treatment response in chronic HBV (CHB) patients with an HVL.

Patients and Methods

The study cohort was 66 HBeAg-positive CHB patients with an HVL (serum HBV DNA >1.9×10⁶ IU/mL) at baseline from our previous prospective cohort study treated with lamivudine (LAM) and adefovir dipivoxil(ADV) (N=31) or entecavir alone (N=35) for ≤96 weeks. The serum HBV RNA level was quantified by TaqMan^® probe-based reverse transcription real-time quantitative polymerase chain reaction at four time points.

Results

The baseline serum HBV RNA level (in log₁₀ copies/mL) in patients treated with LAM+ADV and ETV monotherapy was 8.97±1.22 and 9.15±0.92, respectively. After nucleos(t)ide analog (NA) therapy, the serum HBV RNA level decreased steadily in all patients (week 0 vs week 12, p<0.001; week 12 vs week 24, p=0.010; week 24 vs week 48, p<0.001). Fifty-three (80.3%) patients achieved a virologic response (VR), and 12 (18.2%) achieved HBeAg seroconversion after 96 weeks. Multivariate analyses revealed that the serum HBV RNA level at week 12 could predict HBeAg seroconversion (OR 3.560, 95% CI: 1.39–9.110, p=0.008) and VR (1.908, 1.115–3.265, 0.018) at 96 weeks. Analyses of receiver operating characteristic curves indicated that the serum HBV RNA level 12 weeks after NA treatment had predictive value for HBeAg seroconversion (AUC=0.847, p<0.001) and VR (AUC=0.736, p=0.011).

Conclusion

The serum level of HBV RNA at 12 weeks could predict HBeAg seroconversion and a VR during NA treatment in CHB patients with an HVL.

Keywords:

• HBV RNA
• HBeAg seroconversion
• virological response
• high viral load
• nucleos(t)ide analogs

Acknowledgments

We thank Dr Yegui Jiang for providing participants from Southwest Hospital, Third Military Medical University; Dr Yonghong Zhang for providing participants from Second Xiangya Hospital, Central South University; Dr Fangfang Lv for providing the participants from Sir Run Run Shaw Hospital, Zhejiang University. Xin Ji and Muye Xia are co-first authors for this study.

Disclosure

The authors report no conflicts of interest in this work.