Li Xiangyong, Luo Jie, Zhu Changhao, Wu Yuankai, Li Zhanyi, Jie Yusheng, Zhang Yeqiong, Lin Guoli, Li Xinhua, Zhang Ying, Shu Xin
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
Department of Hepatology, Shenzhen Luohu People's Hospital, Shenzhen, Guangdong 518020, P.R. China.
Exp Ther Med. 2019 Feb;17(2):1196-1205. doi: 10.3892/etm.2018.7081. Epub 2018 Dec 11.
In the present study, the efficacy and safety of tenofovir disoproxil fumarate (TDF) switch therapy were assessed in patients with chronic hepatitis B exhibiting a suboptimal response to adefovir (ADV)-based combination therapy. First, the efficacy of the TDF switch therapy was retrospectively evaluated in 50 patients with chronic hepatitis B who failed to respond to ADV-based combination treatment. Among those, 48 patients with a median age of 35 years were hepatitis B e antigen (HBeAg)-positive and 17, 14 and 19 patients were previously treated with lamivudine (LAM) plus ADV, telbivudine plus ADV and entecavir (ETV) plus ADV, respectively. A total of 41 patients were treated with TDF alone and 9 with TDF plus ETV. The median time of follow-up was 102 weeks. The primary end-point was the cumulative probability of achieving a complete virologic response (CVR). The secondary end-points were the rate of alanine aminotransferase (ALT) normalization, HBeAg seroconversion in HBeAg-positive patients, and the plasma levels of creatinine and creatine kinase. The mean serum hepatitis B virus DNA levels prior to initiation of the TDF switch therapy were 4.8±1.6 logIU/ml. The cumulative probability of achieving a VR at 24, 48, 96 and 108 weeks was 52.0, 76.0, 89.8 and 94.9%, respectively. The cumulative probability of normalization of ALT at 12, 24, 36, 48, 60,72, 84, 96, 108, 120 and 132 weeks was 34, 44, 50, 58, 66, 70, 74, 80, 90, 92 and 94%, respectively. HBeAg seroconversion was achieved in 5 patients. During the follow-up, 6 patients suffered from a virologic breakthrough, 3 patients failed to respond to the TDF treatment and the remaining patients were able to obtain VR following the continuation of TDF treatment. Slightly elevated serum levels of creatinine were observed in one patient, whereas creatine kinase activity did not increase in any of the subjects. In conclusion, TDF switch therapy is efficient and safe for patients with chronic hepatitis B with a suboptimal response to ADV-based combination therapy.
在本研究中，对接受基于阿德福韦（ADV）的联合治疗反应欠佳的慢性乙型肝炎患者，评估了替诺福韦酯（TDF）转换治疗的疗效和安全性。首先，对50例接受基于ADV的联合治疗无反应的慢性乙型肝炎患者进行回顾性评估，以确定TDF转换治疗的疗效。其中，48例患者（中位年龄35岁）乙肝e抗原（HBeAg）阳性，分别有17例、14例和19例患者曾接受拉米夫定（LAM）联合ADV、替比夫定联合ADV以及恩替卡韦（ETV）联合ADV治疗。41例患者单独接受TDF治疗，9例接受TDF联合ETV治疗。中位随访时间为102周。主要终点是实现完全病毒学应答（CVR）的累积概率。次要终点包括丙氨酸氨基转移酶（ALT）复常率、HBeAg阳性患者的HBeAg血清学转换以及肌酐和肌酸激酶的血浆水平。开始TDF转换治疗前，血清乙肝病毒DNA平均水平为4.8±1.6 logIU/ml。在24周、48周、96周和108周时实现病毒学应答（VR）的累积概率分别为52.0%、76.0%、89.8%和94.9%。在12周、24周、36周、48周、60周、72周、84周、96周、108周、120周和132周时ALT复常的累积概率分别为34%、44%、50%、58%、66%、70%、74%、80%、90%、92%和94%。5例患者实现了HBeAg血清学转换。随访期间，6例患者出现病毒学突破，3例患者对TDF治疗无反应，其余患者继续接受TDF治疗后能够获得VR。1例患者血清肌酐水平略有升高，而所有受试者的肌酸激酶活性均未升高。总之，对于接受基于ADV的联合治疗反应欠佳的慢性乙型肝炎患者，TDF转换治疗有效且安全。
