Long-term efficacy of entecavir in adefovir-refractory chronic hepatitis B patients with prior lamivudine resistance
Long-term efficacy of entecavir in adefovir-refractory chronic hepatitis B patients with prior lamivudine resistance
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DOI：
10.1111/j.1365-2893.2011.01479.x
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发表时间：
2011-10-01
影响因子：
2.5
通讯作者：
Park, C. K.
中科院分区：
文献类型：
--
作者：
Park, J. W.;Kim, H. S.;Park, C. K.
本研究旨在评价恩替卡韦(ETV)对拉米夫定(LMV)耐药的阿德福韦(ADV)耐药慢性乙型肝炎(CHB)患者的长期疗效。连续纳入55例有LMV耐药史的ADV难治性CHB患者，这些患者每天接受ETV 1 mg的抢救治疗，疗程至少12个月。44名患者为男性，他们的中位年龄为47岁(25-69岁)。肝硬变10例，乙肝e抗原(HBeAg)阳性46例。中位HBVDNA水平为6.6(4.3-8.0)log(10)拷贝/毫升，ETV治疗的中位持续时间为24(12-47)个月。6个月、12个月、24个月和36个月的累积病毒学应答率分别为18%、29%、58%和75%。46例HBeAg阳性患者中有10例发生HBeAg丢失(21.7%)。在多变量分析中，只有3个月后的初始病毒学应答仍是病毒学应答的独立预测因素(RR 3.143；95%CI 1.387~7.120；P=0.006)。病毒学应答3个月的患者不仅病毒学应答的概率显著高于病毒学应答的患者(P<；0.001)，而且病毒学突破的概率也低于早期无应答的患者(P=0.043)。29例患者在随访期内观察到病毒突破。6个月、12个月、24个月和36个月的累积突破率分别为0%、15%、45%和73%。ETV单一疗法在最初的病毒学应答病例中可能相当有效，但在有LMV耐药史的ADV难治性CHB患者中，ETV耐药性的频繁出现会削弱其疗效。
This study aimed to evaluate the long-term efficacy of entecavir (ETV) in adefovir (ADV)-refractory chronic hepatitis B (CHB) patients with prior lamivudine (LMV) resistance. A total of 55 ADV-refractory CHB patients with prior LMV resistance, who received rescue therapy with ETV 1 mg daily for at least 12 months, were consecutively enrolled and analysed. Forty-four patients were men, and their median age was 47 (25-69). Ten patients had liver cirrhosis and 46 patients were positive for hepatitis B e antigen (HBeAg). Median hepatitis B virus DNA levels were 6.6 (4.3-8.0) log(10) copies/mL, and the median duration of ETV therapy was 24 (12-47) months. Cumulative virologic response rates at 6, 12, 24 and 36 months were 18%, 29%, 58% and 75%, respectively. HBeAg loss occurred in 10 (21.7%) of 46 HBeAg-positive patients. In multivariate analysis, only initial virologic response at 3 months remained as an independent predictor for virologic response (RR 3.143; 95% CI 1.387-7.120; P = 0.006). The patients with a virological response at 3 months had not only a significantly higher probability of achieving a virologic response (P < 0.001) but also lower probability of experiencing a virologic breakthrough (P = 0.043) than the patients without an early response. Viral breakthrough was observed in 29 patients during the follow-up period. Cumulative breakthrough rates at 6, 12, 24 and 36 months were 0%, 15%, 45% and 73%, respectively. ETV monotherapy may be considerably efficacious in cases with an initial virological response but its efficacy is attenuated by frequent emergence of ETV resistance in ADV-refractory CHB patients with prior LMV resistance.