拉米夫定耐药后的治疗抉择

[AASLD2010]拉米夫定耐药后的治疗抉择——Jordan Feld教授访谈

文章导读：令人担心的是，拉米夫定耐药患者服用恩替卡韦后出现耐药的比例非常高，每年大约达到15%，这与拉米夫定单药治疗出现耐药的比例相似。正因为如此，我们不愿意让这些患者改用恩替卡韦。

　　Hepatology Digest: For lamivudine resistant patients is it better for them to be put on lamivudine plus adefovir or directly to entecavir solely?

　　《国际肝病》：对于拉米夫定耐药患者来说，更好的选择是拉米夫定联合阿德福韦治疗还是恩替卡韦单药治疗？

　　Dr Jordan Feld : The concern with putting the patients on entecavir is that the rate of resistance in lamivudine resistant patients will be quite high， similar to that seen with lamivudine monotherapy up to 15% annually. For this reason， I would be very reluctant to switch these patients to entecavir. I think the two safer options are to add adefovir with lamivudine or switch them to tenofovir. If one chooses to use entecavir in this scenario， it is critical to remember to use the higher dose (1 mg daily) – this unfortunately also increases the cost.
　　Jordan Feld博士：令人担心的是，拉米夫定耐药患者服用恩替卡韦后出现耐药的比例非常高，每年大约达到15%，这与拉米夫定单药治疗出现耐药的比例相似。正因为如此，我们不愿意让这些患者改用恩替卡韦。我认为有两个较为安全的选择：加用阿德福韦酯或改用替诺福韦。如果要选用恩替卡韦，特别需要注意的是要使用较高剂量（1 mg/d），这就无疑增加了治疗成本。

　　Hepatology Digest: China still uses a lot of lamivudine. How can we minimize the risk of relapse when we take patients off therapy?
　　《国际肝病》：目前在中国，仍然在大量应用拉米夫定。那么，当患者停止治疗时，我们如何最大限度的降低复发风险？
　　Dr Jordan Feld: Recent European data particularly from the Netherlands have shown quite convincingly that even after 6 months of consolidation therapy after HBeAg seroconversion， most patients relapse when they stop treatment. A 70% to 90% relapse rate is estimated and because of this I think unless you have compelling reasons not to， we really like to prolong therapy until HBsAg clearance. Alternatively you could stop therapy and follow them up thoroughly to see if they fall into that 20-30% category and are able to have a maintained response off lamivudine. That is certainly another reasonable approach but it is just critical that they are followed once lamivudine is stopped.
　　Jordan Feld博士：最近欧洲的数据，特别是来自荷兰的数据非常有说服力，他们的数据表明HBeAg血清学转换后巩固治疗6个月，大部分患者仍然会出现复发。估计复发率约为70%～90%，正因为如此，我认为除非存在非常强力的理由，否则应该延长治疗直至HBsAg清除。当然，你也可以选择停止治疗并对患者进行长期的随访，以观察患者是否进入20%～30%无复发组以及确定患者能够对拉米夫定保持长期应答。可以看出随访在拉米夫定停药患者是非常合理、重要的环节。

　　Hepatology Digest: What is your comment on the use of HBsAg for the endpoint of Hepatitis B treatment?
　　《国际肝病》：您对HBsAg作为乙肝治疗终点有什么看法？
　　Dr Jordan Feld: It certainly is becoming the endpoint of choice. Although it is not the most common endpoint， it is definitely very attractive. This is because we know from long term data that with HBsAg clearance patients do very well; the only problem with this is that we have to maintain patients on therapy for a very long time to achieve it. Hopefully the introduction of HBsAg titers in the future will help determine who is likely to clear HBsAg over time.
　　Jordan Feld博士：HBsAg当然作为首选的治疗终点。虽然它不是常见的治疗终点，但是我们已经把它作为最理想的终点。因为我们知道，从长期的数据来说，HBsAg清除的患者预后非常好，惟一的问题就是患者必须接受很长时间的治疗才能达到这种疗效。未来有希望通过HBsAg滴度的测量来帮助确定哪些患者可能获得持久的HBsAg清除。

　　Hepatology Digest: What are your views on recent studies concerning entecavir causing lactic acidosis as a side effect?
　　《国际肝病》：您对最近报道的恩替卡韦会导致乳酸酸中毒有什么看法？
　　Dr Jordan Feld: As highlighted by Dr Hoofnagle， they were not classical cases of lactic acidosis and I think his comments are valid. However they certainly had some features of the lactic acidosis syndrome and this would make me think twice about using entecavir in patients with decompensated cirrhosis. I don’t think that there is any significant risk of lactic acidosis in patients without decompensated disease.
　　Jordan Feld博士：正如Hoffnagle博士所强调那样，乳酸酸中毒不是恩替卡韦典型的不良反应，我认为这是非常有根据的。然而确实存在乳酸酸中毒的一些特征。所以，我只是在肝硬化失代偿患者应用恩替卡韦时认真考虑一下。我认为在无失代偿的患者，没有发生乳酸酸中毒的风险。