Li Ping, Geng Jiabao, Li Wei, Xu Xiaobing, Zhang Xin, Zheng Wenkai, Yu Yuecheng, Yang Zhiguo, Wang Maorong
Department of Liver Disease Center, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
Department of Infection Disease Center, Henan Province People's Hospital, Zhengzhou, Henan Province, China.
Virol J. 2017 Apr 4;14(1):68. doi: 10.1186/s12985-017-0739-z.
The amino acid substitution at position 181 of the Hepatitis B virus (HBV) polymerase is a multi-drug resistance affecting both the L-nucleoside and acyclic phosphonate nucleotide groups. Data is limited on the efficacy of entecavir (ETV) rescuing chronic hepatitis B (CHB) patients with rtA181T/V mutation.
Thirty-one patients with rtA181T/V mutation and 25 patients with rtA181T/V and rtN236T mutation were enrolled. Virological, serological and biochemical outcomes of ETV rescue therapy over 12 months in CHB patients with rtA181T/V mutation strains were investigated. All patients were treated with ETV 0.5 mg/day for 12 months and scheduled follow-up every 3 months. Patients' characteristics, laboratory tests results and clinical outcomes were collected and compared.
After emergence of rtA181T/V mutant, serum HBV DNA levels increased over 4 log10 IU/mL, but the total bilirubin, alanine aminotransferase (ALT) levels raised moderately. No significant difference in baseline characteristics was observed between the rtA181T/V group and rtA181T/V + rtN236T group. After 12 months rescue therapy, total 85.7% (48/56) patients achieved HBV DNA undetectable. No significant difference in the mean reduction of serum HBV DNA and biochemical response was observed between both groups (3.59 ± 1.85 vs. 3.76 ± 2.15 log10 IU/ml; P = 0.756 and 90.3 vs. 80.0%; P = 0.272, respectively). The mean HBV DNA reduction, HBsAg and ALT levels were also similar between different rtA181T/sW172 mutations (P > 0.05). HBV DNA level is the only predictor of 12 months antiviral outcomes (odds ratio 6.723, P = 0.022).
The results of the present study suggested that ETV is efficient in rescuing rtA181T/V mutation CHB patients. HBV DNA level could predict viral clearance at the 12 month.
乙型肝炎病毒（HBV）聚合酶第181位氨基酸替换是一种影响L-核苷和无环膦酸核苷酸类药物的多药耐药性。关于恩替卡韦（ETV）挽救rtA181T/V突变慢性乙型肝炎（CHB）患者疗效的数据有限。
纳入31例rtA181T/V突变患者和25例rtA181T/V及rtN236T突变患者。研究rtA181T/V突变株CHB患者接受ETV挽救治疗12个月的病毒学、血清学和生化结果。所有患者接受ETV 0.5mg/天治疗12个月，每3个月定期随访。收集并比较患者的特征、实验室检查结果和临床结局。
rtA181T/V突变出现后，血清HBV DNA水平升高超过4 log10 IU/mL，但总胆红素、丙氨酸氨基转移酶（ALT）水平中度升高。rtA181T/V组和rtA181T/V+rtN236T组在基线特征上未观察到显著差异。12个月挽救治疗后，共有85.7%（48/56）的患者HBV DNA检测不到。两组间血清HBV DNA平均下降幅度和生化应答无显著差异（分别为3.59±1.85 vs. 3.76±2.15 log10 IU/ml；P=0.756和90.3% vs. 80.0%；P=0.272）。不同rtA181T/sW172突变之间的HBV DNA平均下降幅度、HBsAg和ALT水平也相似（P>0.05）。HBV DNA水平是12个月抗病毒结局的唯一预测指标（优势比6.723，P=0.022）。
本研究结果提示ETV对挽救rtA181T/V突变CHB患者有效。HBV DNA水平可预测12个月时的病毒清除情况。
