Center of Infectious Diseases, Division of Molecular Biology of Infectious Diseases, State Key Laboratory of Biotherapy (Sichuan University), West China Hospital, Sichuan University, Chengdu, Sichuan, China.
J Viral Hepat. 2010 Mar;17(3):178-84. doi: 10.1111/j.1365-2893.2009.01164.x. Epub 2009 Jul 28.
At present, there is no consensus treatment for patients who have poor response to Adevofir dipivoxil (ADV) monotherapy and no ADV-associated mutation. The purpose of this study was to evaluate the effect of a new therapeutic strategy combining Lamivudine (LAM) and ADV in patients with HBeAg-positive chronic hepatitis B (CHB) and poor response to ADV monotherapy. Thirty-one patients with chronic hepatitis B with HBV DNA > or = 10(4) copies/mL after 48 weeks of ADV monotherapy were included and received ADV plus LAM for 24 weeks. Compared with ADV monotherapy, ADV + LAM had an improved response rate at weeks 12 and 24 - compared with baseline, the median decrease in HBV-DNA level at week 12 and 24 were 1.27 and 2.03 log respectively. The virological response (VR) rate (HBV-DNA level <10(3) copies/mL) was 6.5% and 35.5% at weeks 12 and 24, respectively; the biochemical response (BR) rate (normalization of alanine aminotransferase levels) was 67.8% and 100%, respectively; the HBeAg loss rate was 6.9% and 34.5%, respectively; and the seroconversion rate (from HBeAg to HBeAb) was 3.5% and 6.9% respectively. No ADV-associated mutation was detected at baseline. After combination therapy for 24 weeks, no LAM-resistant or ADV-resistant mutations were detected. Only one patient had a mild adverse reaction. In conclusion, optimization of therapy combining LAM and ADV may be a good choice for patients with hepatitis B who have a poor response to ADV monotherapy.
目前，对于阿德福韦酯（ADV）单药治疗应答不佳且无 ADV 相关突变的患者，尚无共识的治疗方法。本研究旨在评估拉米夫定（LAM）联合 ADV 的新治疗策略在 ADV 单药治疗应答不佳的 HBeAg 阳性慢性乙型肝炎（CHB）患者中的疗效。纳入 31 例 ADV 单药治疗 48 周后 HBV DNA >或= 10（4）拷贝/ml 的慢性乙型肝炎患者，给予 ADV 联合 LAM 治疗 24 周。与 ADV 单药治疗相比，ADV+LAM 在治疗 12 周和 24 周时的应答率更高——与基线相比，HBV-DNA 水平在第 12 周和第 24 周的中位数下降分别为 1.27 和 2.03 log。病毒学应答（VR）率（HBV-DNA 水平 <10（3）拷贝/ml）分别为治疗 12 周和 24 周时的 6.5%和 35.5%；生化学应答（BR）率（丙氨酸氨基转移酶水平正常化）分别为 67.8%和 100%；HBeAg 丢失率分别为 6.9%和 34.5%；HBeAg 至 HBeAb 的血清学转换率分别为 3.5%和 6.9%。基线时未检测到 ADV 相关突变。联合治疗 24 周后，未检测到 LAM 耐药或 ADV 耐药突变。仅有 1 例患者出现轻度不良反应。结论，LAM 联合 ADV 的优化治疗可能是 ADV 单药治疗应答不佳的乙型肝炎患者的良好选择。
