拉米夫丁+干扰素联合用药减少抗药%

liver411

拉米长期服用会造成抗药变异, 最近研究文章一再登载 拉米+干扰 联合用药会减少拉米抗药的%. (看看有时间翻一翻)



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Epivir-HBV Plus Interferon Decreases Development of HBV Resistant to Epivir-HBV



By Brian Boyle, MD



Epivir-HBV (lamivudine) is a potent inhibitor of hepatitis B virus (HBV) replication and has been shown in studies to rapidly suppress viral replication and improve liver histology in both HBeAg positive and anti-HBe positive patients with chronic HBV.



Unfortunately, prolonged monotherapy with Epivir-HBV frequently results in the development of HBV variants that are resistant to Epivir-HBV, with amino-acid substitutions both in the B domain (L528M) and in the YMDD motif of the C domain (M552I and M552V) of the viral DNA polymerase.



Studies indicate that the development of Epivir-HBV resistance increases over time and that once resistance occurs HBV disease progression recurs. In a study published in the Journal of Hepatology, Epivir-HBV and interferon (IFN) combination therapy was compared to Epivir-HBV monotherapy to determine if the combination treatment improved efficacy and reduced the emergence of HBV mutants resistant to HBV.



The study enrolled 50 patients with anti-HBe-positive chronic HBV. The patients were randomized to be treated for 12 months with Epivir-HBV at 100 mg/day or with IFN at 5 million units three times per week plus Epivir-HBV at 100 mg/day. All patients had a liver biopsy showing active disease within 24 months before admission to the study. Further, prior to beginning therapy, all patients were positive for HBV DNA and had an elevated alanine aminotransferase (ALT) level.



In both groups of patients, a rapid decline of HBV viremia occurred with treatment and after 4 weeks of treatment, HBV DNA levels were undetectable in all patients. Further, normal ALT values were achieved within 6 months in 24 of 26 patients on Epivir-HBV and in 21 of 24 on Epivir-HBV plus IFN.



In the Epivir-HBV monotherapy group, 5 patients showed reappearance of HBV DNA in the serum after 6 to 10 months of therapy and in these patients viral breakthrough was followed by an increase of ALT levels. Sequence analysis of serum HBV DNA obtained before therapy and during breakthrough revealed the emergence of Epivir-HBV resistant variants in all patients, with a methionine to valine substitution in the YMDD amino acid motif (M552V), a change of leucine to methionine at amino acid position 528 (L528M) in the B domain of viral reverse-transcriptase in four patients, and a single methionine to isoleucine substitution (M552I) in the remaining patients.



Overall, 21/26 patients (81%) treated with LAM showed end-of-treatment response compared to 24/24 patients (100%) treated with the combination therapy. After therapy was discontinued, however, most of the patients relapsed and the response rate after 6 months was 17% in the Epivir-HBV plus interferon group and 19% in the Epivir-HBV group. The combination treatment was relatively well tolerated and all patients completed therapy.



The authors conclude, "in this study, the [Epivir-HBV plus interferon] combination and Epivir-HBV monotherapy regimens appeared to effectively suppress HBV replication and provided a similar response rate (~20%) after a 6 month follow-up; in fact, the majority of responders in both groups relapsed after therapy discontinuation, irrespective of treatment regimen. Interestingly, however, combination therapy appeared to prevent the selection of YMDD variants; no patient in the combination, but five (19%) in the [Epivir-HBV] treated group, developed HBV resistance due to the selection of YMDD variants.



"Therapeutic efficacy was lost with the emergence of the [Epivir-HBV] resistant variants, and the disease rekindled with the same pre-treatment fluctuating biochemical and virological profile."



06/05/02



Reference

T Santantonio and others. Lamivudine/interferon combination therapy in anti-HBe positive chronic hepatitis B patients: a controlled pilot study. Journal of Hepatology 2002; 36:799-804.





HIV AND HEPATITIS COM



(hbvhbv.net 内部参考)

可可

看了一下，我简单的试着翻译一下。有误请大家指正。



这是一个由50个anti-Hbe 阳性的慢性乙肝病人参加的研究。病人是随机选择的，治疗12个月，分成了两组，一组单独使用拉米100mg/天，另一组使用干扰素500万单位每周三次另加拉米100mg/天。所有的病人进行了肝组织活检，病人HBVDNA都为阳性，而且ALT处在较高水平。



两个组的病人经过四个月的治疗后。HBVDNA快速下降直至检测不到，6个月内，肝功都达成正常，单独使用拉米的ALT在24至26之间，联合使用拉米和IFN的ALT在21至24之间。



单独使用拉米的一组，其中5 个病人在治疗6个月至10个月后，从血清中检测出HBVDNA，并伴随着ALT升高。出现不同位置的YMDD变异。



联合使用拉米和干拢素的病人没有出现YMDD变异。



停药6个月后，两组所有病人中大约20%的病人病情复发。事实上绝大部多数的病人在停药后病情复发。

龙城泥巴

打击啊~，我正在这样联合用药，而且初见效果。

寂寞的精灵

我联合用药已经结束

医生只给我多开了3个月的拉米

要我检查看有无变异在开

郁闷