Pan H-Y, Pan H-Y, Song W-Y, Zheng W, Tong Y-X, Yang D-H, Dai Y-N, Chen M-J, Wang M-S, Huang Y-C, Zhang J-J, Huang H-J
Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
Department of Medicine, Pujiang People's Hospital, Zhejiang, China.
J Viral Hepat. 2017 Nov;24 Suppl 1:29-35. doi: 10.1111/jvh.12794.
Chronic hepatitis B (CHB) patients with higher hepatitis B virus (HBV) load (higher viral load [HVL], HBV DNA ≥1 × 10 copies/mL) require antiviral therapy, but data for evaluating the long-term outcome of this therapy with antiviral agents remain limited. We comparatively evaluated the efficacy and the safety of nucleoside analogues in 179 noncirrhotic CHB patients with HVL over 5 years. The HBeAg-positive (n = 104) or HBeAg-negative (n = 75) patients were treated consecutively with telbivudine (LdT, n = 88) or entecavir (ETV, n = 91) and evaluated for viral response, drug resistance and safety. HBV DNA, viral serology, biochemistries, HBV mutation and off-therapy relapse were determined. The cumulative rates of HBV DNA negativity were 86.4% and 94.5% for LdT and ETV at year 5, respectively. The rates of early viral response (EVR, HBV DNA <10 copies/mL at month 6) under LdT and ETV treatments were 58.0% and 34.1%, respectively (P < .05). Hepatitis B e antigen (HBeAg) and Hepatitis B surface antigen (HBsAg) loss-seroconversions were 47.7% and 18.2% on LdT and 16.5% and 2.2% on ETV (P < .01). Eighteen patients (age 28.2 ± 3.1) experienced HBsAg loss-seroconversion, followed by 33 ± 4.6 month off-therapy without a relapse. Viral mutations and serum creatine kinase elevation were 9.1% and 8.0% on LdT, but only 1.1% and 0% on ETV. Both LdT and ETV suppressed HBV replication in HVL CHB patients within 5 years. LdT therapy achieved a higher EVR, HBeAg and HBsAg seroconversion, especially in the younger patients, whereas ETV caused lower drug resistance and fewer adverse events. This finding might help to identify the optimal treatment for CHB patients with HVL.
乙肝病毒（HBV）载量较高（高病毒载量[HVL]，HBV DNA≥1×10拷贝/mL）的慢性乙型肝炎（CHB）患者需要进行抗病毒治疗，但评估抗病毒药物长期疗效的数据仍然有限。我们比较评估了179例非肝硬化HVL CHB患者使用核苷类似物超过5年的疗效和安全性。HBeAg阳性（n = 104）或HBeAg阴性（n = 75）患者连续接受替比夫定（LdT，n = 88）或恩替卡韦（ETV，n = 91）治疗，并评估病毒反应、耐药性和安全性。测定HBV DNA、病毒血清学、生化指标、HBV突变及停药后复发情况。治疗5年时，LdT组和ETV组HBV DNA阴性累积率分别为86.4%和94.5%。LdT和ETV治疗下的早期病毒学应答（EVR，治疗6个月时HBV DNA<10拷贝/mL）率分别为58.0%和34.1%（P<0.05）。LdT组和ETV组的HBeAg和HBsAg血清学转换率分别为47.7%和18.2%、16.5%和2.2%（P<0.01）。18例患者（年龄28.2±3.1）发生HBsAg血清学转换，随后停药33±4.6个月无复发。LdT组病毒突变率和血清肌酸激酶升高率分别为9.1%和8.0%，而ETV组仅为1.1%和0%。LdT和ETV均可在5年内抑制HVL CHB患者的HBV复制。LdT治疗获得了更高的EVR、HBeAg和HBsAg血清学转换率，尤其是在年轻患者中，而ETV引起的耐药性更低，不良事件更少。这一发现可能有助于确定HVL CHB患者的最佳治疗方案。
