Hepatology Digest: As HBV therapy has developed， a more personalized approach is critical. What factors are important to follow-up after therapy to prevent resistance? 《国际肝病》：随着HBV感染治疗的发展，个体化治疗非常关键。那么治疗随访中，防止耐药发生的最关键因素是什么？ Prof. Zoulim: If we want to prevent resistance in patients who are already on treatment， first of all the virologic monitoring is really critical and especially if you are using a drug with a low barrier to resistance such as lamivudine or adefovir or telbivudine. But obviously the best way to prevent drug resistance is by starting with a drug with a high barrier to resistance such as tenofovir and entecavir and then the rate of resistance is much lower. Importantly， you need to make sure the patient adheres to treatment and additionally the treatment must be efficacious in that given patient which requires very good virologic monitoring. Zoulim教授：如果我们想防止在治患者耐药的发生，病毒学检测是关键；特别是对于一些正在服用低基因耐药屏障的药物的患者，例如拉米夫定、阿德福韦酯或替比夫定等尤其重要。防止耐药最好的方法是，开始治疗时就使用高基因耐药屏障的药物，例如替诺福韦和恩替卡韦，这样耐药率就会大大降低；其中，重要的是，你需要确保患者坚持服药，再加上很好的病毒学监测，治疗肯定会有效。 Hepatology Digest: Unfortunately in China， entecavir is very expensive and tenofovir is not yet licensed so we still use a lot of lamivudine and adefovir. So for us， what advice can you offer to prevent resistance in these circumstances? 《国际肝病》：然而在中国，恩替卡韦价格昂贵，替诺福韦尚未上市；因此，我们只能使用拉米夫定和阿德福韦酯。您能给我们一些适合中国的防止耐药发生的建议吗？ Prof. Zoulim: You have two drugs that are not perfect. Lamivudine has no side effects and is quite potent in the early stage but it is associated with a very high rate of resistance. On the other hand， adefovir has a slow antiviral activity but with a lower rate of resistance. What I would advise in China where you only have access to these two drugs is combination therapy right from the start. Begin with a combination therapy of lamivudine and adefovir because they are complimentary drugs in terms of resistance as they do not share cross-resistance. One is more potent， lamivudine， so you have a very strong antiviral effect and adefovir will cover the potential resistance to lamivudine. In this situation this is what I would do. That is what was done way back in the past (five years ago) in Europe， when entecavir and tenofovir were not available. Zoulim教授：中国现有两种药，但不完美。拉米夫定副作用小、早期应用效果显著，但易发生耐药。阿德福韦酯疗效发生缓慢，但耐药发生率低。所以我的建议是，从开始就应该正确联合应用这些药物。治疗开始联合应用拉米夫定和阿德福韦酯，这样二者互补不会发生交叉耐药。更重要的是，拉米夫定抗病毒效果显著，而阿德福韦酯恰好可拮抗拉米夫定的耐药性。5年前在欧洲，恩替卡韦和替诺福韦也还未上市，我们就曾联合应用这两种药物。 Hepatology Digest: Will future EASL Guidelines pay attention to Harry Janssen’s work regarding therapy duration beyond six months? 《国际肝病》：将来的EASL指南将会采纳Harry Janssen教授关于治疗周期应该长于6个月的意见吗？ Prof. Zoulim:The advantage of interferon is that you have a finite duration of therapy which may be six or twelve months. This is good compared with the nucleoside/nucleotide analogues which require long-term， several years， of therapy. The problem with interferon is that the rate of sustained response is low when you stop treatment and many patients do relapse. But this is a way， especially in young patients， if you have good predictive factors such as high ALT， low HBV DNA levels， to try with interferon for one year and depending on viral genotype and the evolution of HBsAg level， you can either stop early with interferon or extend therapy to try to achieve anti-HBe seroconversion or even HBsAg loss. As we say， finite duration therapy， but you can manage your patient and if therapy fails you can fall back on NA therapy. Zoulim教授：干扰素的优势在于你有明确的治疗周期6个月或12个月；相对而言，核苷（酸）类似物则要求长达几年的治疗。干扰素治疗的问题在于停止治疗后持久应答率低，许多患者会反弹。然而，特别是年轻患者，如果患者有好的预测有效的指标例如高ALT水平和低HBV DNA，可以根据病毒基因型和HBsAg水平应用1年后，可以早期停止治疗或者继续治疗直至发生HBeAg血清学转换甚至HBsAg清除。以我之见，虽然为有限疗程，但是你仍然可以继续管理患者，如果治疗失败，还可以改用核苷（酸）类似物治疗。 作者: 咬牙硬挺 时间: 2012-5-17 13:19
