Fung James, Lai Ching-Lung, Yuen John Chi-hang, Wong Danny Ka-Ho, Tanaka Yasuhito, Mizokami Masashi, Yuen Man-Fung
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
Antivir Ther. 2007;12(1):41-6.
To determine differences in Chinese patients treated with adefovir (ADV) monotherapy or ADV in combination with lamivudine (3TC) after development of resistance to 3TC, with respect to biochemical improvement, HBV DNA suppression and development of subsequent ADV resistance.
All hepatitis B patients with 3TC resistance treated with ADV for 3 months or more at our centre were included, and monitored 3-6 monthly for biochemical and virological response, and development of ADV resistance.
A total of 56 patients were included, 50% switched to ADV monotherapy and 50% received combination 3TC/ADV therapy. Median follow-up was 15.5 months. Normalization of alanine aminotransferase (ALT) occurred in 25 (89%) patients in the ADV group compared with 24 (86%) in the 3TC/ADV group (P = 0.686). Virological response (VR) was achieved in seven (35%) patients in the ADV group at 12 months compared with five (28%) in the 3TC/ADV group (P = 0.637). By 24 months, seven (64%) patients in the ADV group achieved VR compared with two (40%) in the 3TC/ADV group (P = 0.377). Cumulative probability of developing genotypic ADV resistance in the ADV group at 24 months was 18% compared with 7% in the 3TC/ADV group (P = 0.94).
There was no obvious improvement in ALT normalization and virological suppression or reduction in the development of ADV-resistant mutations with 3TC/ADV therapy compared with ADV monotherapy. Further studies with longer follow-ups are required to determine whether combination 3TC/ADV therapy will reduce the emergence of ADV resistance compared with ADV monotherapy.
确定在拉米夫定(3TC)耐药后接受阿德福韦(ADV)单药治疗或ADV联合3TC治疗的中国患者在生化改善、乙肝病毒(HBV)DNA抑制及后续ADV耐药发生方面的差异。
纳入在本中心接受ADV治疗3个月或更长时间的所有对3TC耐药的乙肝患者,每3至6个月监测生化和病毒学反应以及ADV耐药的发生情况。
共纳入56例患者,50%转为ADV单药治疗,50%接受3TC/ADV联合治疗。中位随访时间为15.5个月。ADV组25例(89%)患者的丙氨酸氨基转移酶(ALT)恢复正常,3TC/ADV组为24例(86%)(P = 0.686)。ADV组12个月时7例(35%)患者实现病毒学应答(VR),3TC/ADV组为5例(28%)(P = 0.637)。至24个月时,ADV组7例(64%)患者实现VR,3TC/ADV组为2例(40%)(P = = 0.377)。ADV组24个月时发生ADV基因型耐药的累积概率为18%,3TC/ADV组为7%(P = 0.94)。
与ADV单药治疗相比,3TC/ADV联合治疗在ALT恢复正常、病毒学抑制或ADV耐药突变发生减少方面无明显改善。需要进行更长时间随访的进一步研究,以确定与ADV单药治疗相比,3TC/ADV联合治疗是否会减少ADV耐药的出现。