Xu Xian-Hua, Li Gai-Li, Qin Yang, Li Qiang, He Fa-Qun, Li Jin-Ye, Pan Quan-Rong, Deng Jie-Yin
Virol J. 2013 May 25;10:162. doi: 10.1186/1743-422X-10-162.
To evaluate the efficacy and safety of Entecavir (ETV) plus adefovir (ADV) for chronic hepatitis B (CHB) patients after multiple nucleos(t)ide analogue (NAs) failure treatment.
Hepatitis B e antigen (HBeAg)-positive patients who had a suboptimal response or developed resistance to two or more previous NAs treatments were included, and all subjects were treated with ETV in combination with ADV for ≥ 24 months. Complete virologic response (CVR) was defined as an undetectability of serum hepatitis B virus (HBV) DNA level during treatment. Safety assessment was based on the increasing of serum creatinine and creatine kinase levels.
A total of 45 eligible patients were included. Twenty-five patients had been treated with lamivudine (LAM) or telbivudine (LdT) and developed genotypic resistance. Resistance to ADV was present in 18 patients and 4 patients had a suboptimal response to ETV. Two patients had a resistance to both LAM and ADV. The cumulative probabilities of CVR at 12 and 24 months of ETV + ADV treatment were 88.9% (40/45) and 97.8% (44/45), respectively. Although one patient failed to achieve CVR, its serum HBV DNA level decreased by 3.3 log copies/mL after 24 months of combination therapy. The cumulative probability of HBeAg seroconversion was 15.6% (7/45) and 26.7% (12/45) at 12 and 24 months of treatment, respectively. History of prior exposure to specific NAs did not make a difference to ETV + ADV treatment outcome. There were no significant adverse events related to ETV + ADV therapy observed in the study subjects.
ETV + ADV can be used as an effective and safe rescue therapy in patients after multiple NA therapy failures, especially in the areas where tenofovir is not yet available.
评估恩替卡韦（ETV）联合阿德福韦酯（ADV）用于接受多种核苷（酸）类似物（NAs）治疗失败的慢性乙型肝炎（CHB）患者的疗效和安全性。
纳入对两种或更多种先前NAs治疗反应欠佳或产生耐药的乙肝e抗原（HBeAg）阳性患者，所有受试者接受ETV联合ADV治疗≥24个月。完全病毒学应答（CVR）定义为治疗期间血清乙型肝炎病毒（HBV）DNA水平不可检测。安全性评估基于血清肌酐和肌酸激酶水平的升高情况。
共纳入45例符合条件的患者。25例患者曾接受拉米夫定（LAM）或替比夫定（LdT）治疗并产生基因型耐药。18例患者对ADV耐药，4例患者对ETV反应欠佳。2例患者对LAM和ADV均耐药。ETV + ADV治疗12个月和24个月时CVR的累积概率分别为88.9%（40/45）和97.8%（44/45）。尽管有1例患者未实现CVR，但联合治疗24个月后其血清HBV DNA水平下降了3.3 log拷贝/mL。治疗12个月和24个月时HBeAg血清学转换的累积概率分别为15.6%（7/45）和26.7%（12/45）。既往接触特定NAs的病史对ETV + ADV治疗结果无影响。研究对象中未观察到与ETV + ADV治疗相关的显著不良事件。
ETV + ADV可作为多种NAs治疗失败患者的有效且安全的挽救治疗方法，尤其是在尚无替诺福韦的地区。
