Kim Jung Ho, Kim Yun Soo, Jung Young Kul, Kim Yeon Suk, Kwon Oh Sang, Ku Yang Suh, Choi Duck Joo, Kim Ju Hyun
Hepatogastroenterology. 2013 Jun;60(124):842-9. doi: 10.5754/hge12917. Epub 2012 Nov 28.
BACKGROUND/AIMS: Sequential antiviral therapy for chronic hepatitis B may lead to the selection of multidrug-resistant mutation. This study was carried out to assess the efficacy of entecavir in patients that have experienced adefovir monotherapy failure after the development of lamivudine resistance.
Fifty-three patients with confirmed genotypic lamivudine-resistant chronic hepatitis B were treated with entecavir. Thirty patients were switched to entecavir directly (LAM-ETV group), whereas the remaining 23 were adefovir-refractory patients who were switched to entecavir (LAM-ADV-ETV group). These 23 patients included 9 patients with inadequate response (ADV-I subgroup) and 14 that exhibited adefovir resistance (ADV-R subgroup).
Significantly greater reductions in HBV DNA levels were observed after 24, 48 and 72 weeks of entecavir therapy in the LAM-ETV group than in the LAM-ADV-ETV group, respectively. However, between these two groups at 48 and 72 weeks, no significant differences were observed in cumulative proportions of virological response or breakthrough, respectively. Furthermore, efficacy of entecavir was not significantly different in the ADV-I and ADV-R subgroups. Four patients in the LAM-ETV group and six patients in the LAM-ADV-ETV group developed genotypic resistance to entecavir.
Entecavir therapy is less effective in adefovir-refractory patients with prior lamivudine resistance than in lamivudine-resistant patients.
背景/目的:慢性乙型肝炎的序贯抗病毒治疗可能会导致多重耐药突变的产生。本研究旨在评估恩替卡韦对拉米夫定耐药后接受阿德福韦单药治疗失败患者的疗效。
53例确诊为拉米夫定基因型耐药的慢性乙型肝炎患者接受恩替卡韦治疗。30例患者直接换用恩替卡韦(拉米夫定-恩替卡韦组),其余23例为阿德福韦难治性患者,换用恩替卡韦(拉米夫定-阿德福韦-恩替卡韦组)。这23例患者包括9例应答不佳患者(阿德福韦-I亚组)和14例出现阿德福韦耐药患者(阿德福韦-R亚组)。
恩替卡韦治疗24、48和72周后,拉米夫定-恩替卡韦组的HBV DNA水平下降幅度分别显著大于拉米夫定-阿德福韦-恩替卡韦组。然而,在48周和72周时,两组之间在病毒学应答或突破的累积比例方面分别未观察到显著差异。此外,恩替卡韦在阿德福韦-I亚组和阿德福韦-R亚组中的疗效无显著差异。拉米夫定-恩替卡韦组有4例患者和拉米夫定-阿德福韦-恩替卡韦组有6例患者出现恩替卡韦基因型耐药。
与拉米夫定耐药患者相比,恩替卡韦治疗对先前拉米夫定耐药且阿德福韦难治的患者疗效较差。