Hosaka Tetsuya, Suzuki Fumitaka, Suzuki Yoshiyuki, Saitoh Satoshi, Kobayashi Masahiro, Someya Takashi, Sezaki Hitomi, Akuta Norio, Tsubota Akihito, Arase Yasuji, Ikeda Kenji, Kumada Hiromitsu
Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.
Intervirology. 2004;47(6):362-9. doi: 10.1159/000080881.
Adefovir dipivoxil (ADV) is a nucleoside analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine-resistant HBV mutants in vitro and in vivo. The aim of this study was to evaluate the efficacy of ADV against lamivudine-resistant mutants and of adefovir and interferon (IFN) add-on to lamivudine for patients with severe acute exacerbation of hepatitis caused by lamivudine-resistant mutants.
Fourteen patients with breakthrough hepatitis were treated with ADV. Four of the 14 patients also received IFN as combined treatment for severe acute exacerbation of hepatitis.
At week 24, serum HBV DNA levels had significantly decreased by a median of over 4.8 log copies/ml in the ADV group and over 5.9 log copies/ml in the ADV + IFN group compared to baseline. The median decrease in alanine aminotransferase (ALT) levels from baseline to week 24 was -1.05 times the upper limit of normal (ULN) in the ADV group [significant at week 24 compared with baseline (p = 0.012)] and -22.3 times the ULN in the ADV + IFN group.
Administration of ADV add-on to lamivudine for patients with breakthrough hepatitis reduced HBV DNA and ALT levels. ADV and IFN add-on to lamivudine could prevent a fatal course in patients with severe acute exacerbation of hepatitis.
阿德福韦酯（ADV）是一种核苷类似物，在体外和体内均可抑制野生型乙型肝炎病毒（HBV）以及对拉米夫定耐药的HBV突变体。本研究旨在评估ADV对拉米夫定耐药突变体的疗效，以及对于由拉米夫定耐药突变体引起的严重急性肝炎加重患者，在拉米夫定基础上加用阿德福韦和干扰素（IFN）的疗效。
14例出现肝炎病情突破的患者接受了ADV治疗。其中4例患者还接受了IFN联合治疗，用于治疗严重急性肝炎加重。
在第24周时，与基线相比，ADV组血清HBV DNA水平显著下降，中位数下降超过4.8 log拷贝/ml，ADV + IFN组下降超过5.9 log拷贝/ml。从基线到第24周，ADV组丙氨酸氨基转移酶（ALT）水平下降的中位数为正常上限（ULN）的-1.05倍[与基线相比，在第24周时有显著差异（p = 0.012）]，ADV + IFN组为ULN的-22.3倍。
对于出现肝炎病情突破的患者，在拉米夫定基础上加用ADV可降低HBV DNA和ALT水平。在拉米夫定基础上加用ADV和IFN可防止严重急性肝炎加重患者出现致命病程。
