Infection and Drug Resistance (Jun 2020)
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
Xin Ji,* Muye Xia,* Bin Zhou, Shi Liu, GuiChan Liao, Shaohang Cai, Xiaoyong Zhang, Jie Peng State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie PengDepartment of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, People’s Republic of ChinaTel +86 20 6278 7428Fax +86 20 8771 9653Email [email protected] 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
