Fung Scott K, Chae Hee Bok, Fontana Robert J, Conjeevaram Hari, Marrero Jorge, Oberhelman Kelly, Hussain Munira, Lok Anna S F
Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109-0362, USA.
J Hepatol. 2006 Feb;44(2):283-90. doi: 10.1016/j.jhep.2005.10.018. Epub 2005 Nov 15.
The incidence and risk factors for adefovir-resistant HBV have not been clearly defined.
To characterize the virologic response to adefovir, to determine the rate of adefovir resistance and to explore factors associated with initial virologic response (IVR) and adefovir resistance.
All hepatitis B patients who received adefovir for > or =6 months at our center were prospectively monitored for virologic response and adefovir resistance.
Forty three patients were included; mean treatment duration was 18 months (range 6-45). Thirty four (79%) patients had prior lamivudine. IVR was observed in 44% patients and associated with higher pretreatment ALT (P = 0.05) and the absence of HBeAg (P = 0.02). Six (14%) patients were found to have adefovir-resistant mutations. The cumulative probability of genotypic resistance to adefovir at month 24 was 22%. Patients with adefovir resistance were more likely to have been switched from lamivudine to adefovir monotherapy (P = 0.01), to be older (P = 0.04), and to be infected with HBV genotype D (P = 0.02).
Roughly 50% of patients failed to achieve IVR on adefovir. The cumulative probability of adefovir resistance at 2 years was 22%. Our data suggest that combination of lamivudine and adefovir may prevent emergence of adefovir resistance in patients with lamivudine-resistant HBV.
阿德福韦耐药性乙型肝炎病毒(HBV)的发病率及危险因素尚未明确界定。
描述对阿德福韦的病毒学反应特征,确定阿德福韦耐药率,并探索与初始病毒学反应(IVR)及阿德福韦耐药相关的因素。
对在本中心接受阿德福韦治疗≥6个月的所有乙型肝炎患者进行前瞻性监测,观察其病毒学反应及阿德福韦耐药情况。
共纳入43例患者;平均治疗时长为18个月(范围6 - 45个月)。34例(79%)患者曾接受拉米夫定治疗。44%的患者出现IVR,且与较高的治疗前丙氨酸氨基转移酶(ALT)水平(P = 0.05)及HBeAg阴性(P = 0.02)相关。6例(14%)患者被发现存在阿德福韦耐药突变。24个月时阿德福韦基因型耐药的累积概率为22%。出现阿德福韦耐药的患者更有可能是从拉米夫定转换为阿德福韦单药治疗(P = 0.01)、年龄较大(P = 0.04)以及感染HBV D基因型(P = 0.02)。
约50%的患者在阿德福韦治疗时未实现IVR。2年时阿德福韦耐药的累积概率为22%。我们的数据表明,拉米夫定与阿德福韦联合使用可能预防拉米夫定耐药HBV患者出现阿德福韦耐药。