Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine
Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine
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DOI：
10.1111/j.1365-2036.2007.03567.x
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发表时间：
2008-02-01
影响因子：
7.6
通讯作者：
Tzourmakliotis, D.
中科院分区：
文献类型：
--
作者：
Manalakopoulos, S.;Bethanis, S.;Tzourmakliotis, D.
研究背景阿德福韦酯单用或阿德福韦与拉米夫定联合治疗HBe抗原(HBe-Ag)阴性的拉米夫定耐药慢性乙型肝炎(CHB)的疗效仍在研究中。目的评价长期单用阿德福韦或联合拉米夫定治疗HBe-Ag阴性、因拉米夫定耐药而取得突破的慢性乙肝患者的安全性和有效性。方法59例患者接受联合治疗，23例在联合治疗3个月后改用阿德福韦。两组患者的基线特征相似。在12个月和24个月时，接受联合治疗的患者中有69%和89%的患者以及接受阿德福韦治疗的患者中有73%和82%的患者血清中有10(4)拷贝/毫升的HBVDNA(P>；0.5)。在12个月和24个月时，接受联合治疗的患者中有81%和79%的患者丙氨酸转氨酶水平恢复正常，而接受阿德福韦治疗的患者中分别有61%和53%的患者丙氨酸转氨酶水平恢复正常(P>；0.50)。在接受阿德福韦单药治疗的5名患者中，有5名患者因阿德福韦耐药突变而在病毒学上取得突破，在接受联合治疗的患者中没有一名患者出现突破(P=0.001)。随访期间无一例发生失代偿性肝病或肝细胞癌。阿德福韦耐药患者再次应用拉米夫定后，HBVDNA下降和生化缓解，但有1例患者在7.5个月后再次出现拉米夫定变异。结论在拉米夫定耐药的HBe-Ag阴性慢性乙肝患者中，由于无病毒耐药，在继续拉米夫定治疗的基础上加用阿德福韦可最大限度地提高抗病毒疗效。
BackgroundThe efficacy of long-term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe-Ag)-negative lamivudine-resistant chronic hepatitis B (CHB) patients is still under investigation.AimTo assess the safety and efficacy of the long-term adefovir treatment alone or in combination with lamivudine in HBe-Ag-negative CHB patients who had developed breakthrough because of lamivudine-resistant mutants.MethodsFifty-nine patients received combination therapy, while 23 switched to adefovir alone after a 3-month course of combination therapy.ResultsThe median follow-up after adefovir's onset was 31 (18-40) months. Baseline characteristics were similar between the two groups. At 12 and 24 months, 69% and 89% of patients receiving combination therapy and 73% and 82% of patients receiving adefovir monotherapy had serum HBV-DNA < 10(4) copies/mL (P > 0.5). Normalization of alanine aminotransferase levels occurred in 81% and 79% of patients receiving combination vs. 61% and 53% receiving adefovir monotherapy at 12 and 24 months, respectively (P > 0.50). Virological breakthroughs because of adefovir-resistant mutants occurred in five patients under adefovir monotherapy and in none receiving combination therapy (P = 0.001). No one developed decompensated liver disease or hepatocellular carcinoma during follow-up. Re-introduction of lamivudine in adefovir-resistant patients achieved reduction in HBV-DNA and biochemical remission, but re-emergence of lamivudine mutants was observed in one patient after 7.5 months.ConclusionIn HBe-Ag-negative CHB patients with lamivudine resistance, adding adefovir to continuing lamivudine therapy maximizes anti-viral efficacy because of absence of viral resistance.