现有直接抗病毒药物（DAA）联合方案治疗丙型肝炎可获得很高的治愈率，通常都超过了90%。在第52届欧洲肝脏研究学会年会现场，德国汉堡大学Joerg Petersen教授告诉我们，正因如此，这些方案之间没有头对头比较研究，大家可以参考指南推荐进行选择。那么初治和经治患者治疗的整体模式是什么呢？详细采访内容如下。

 

The SVR of the existing new direct-acting antiviral agents (DAAs) combination therapies is very high and is usually over 90%. That' s why there are no head-to-head studies with these new treatments, said Professor Joerg Petersen from University of Hamburg, Germany, at the 52nd EASL Annual Meeting, and he suggested to refer to the guidelines when choosing therapies. Then what are the general treatment patterns for naive patients and experienced patients? Please see more interview details as follows. 

 

《国际肝病》：患者确诊感染丙型肝炎后，如何保证他们能够及时获得有效的治疗？

 

Hepatology Digest：How could the patients get access to timely and efficient treatment after they are diagnosed with Hepatitis C?

 

Petersen教授：（当患者诊断为HCV感染时），需要确定其是否为慢性感染，因此我们需要间隔6个月复查RNA。DAA在急性丙型肝炎方面目前没有应用的适应证，所以我们需要等待6个月。另外，这还与欧洲不同国家的医疗保险系统和医疗系统有关。例如在德国，对于慢性感染的患者，在治疗上没有限制--也就是说可以在疾病的很早阶段就开始治疗。但在其他欧洲国家的情况却有很大区别，有些限制于晚期肝病。这一点现在已经在发生变化，因为大部分晚期肝病患者已经得到了治疗。因此在各个欧洲国家，对于处于肝纤维化早期阶段的患者的治疗之门也正在打开。

 

Professor Petersen: Chronicity is one point, so we need to see RNA detection for six months. There's no label of medication for acute hepatitis C for the DAA so far, so we will wait 6 months. And then it depends on different health insurance systems, healthcare systems from different European countries. I can only tell you about the situation in Germany, for example, and when we have a chronic patient, there's no restriction in treatments-we can start very early on. But it is very different in other European countries because there's some restriction to advanced liver disease. This is changing now because most of the patients have been treated already-many of those advanced liver disease patients have been treated in the past so the door is opening to even earlier fibrosis stages in different European countries. 

 

我坚信我们应该治疗每一个患者，不考虑纤维化分期、合并感染状态。很幸运在德国，从一开始我们就有条件这么做，所以没有限制。目前唯一的限制是需要隔6个月复查HCV RNA来判定是否是慢性HCV感染，但对于转氨酶、纤维化分期和年龄等没有限制。

 

当然，对于一个80岁或85岁、没有任何肝病迹象的慢性HCV感染者，是否还需要治疗，有待商榷。但如果患者本人或家属有治疗意愿，那么就有治疗适应证。我想这一点很重要。

 

而最重要的是，WHO提出在世界上某些地区根除丙型肝炎，我们能够更接近这个可能性，特别需要治疗一些特殊的人群，如静脉药瘾者或监狱里的囚犯，因为这些人群的传播率很高，需要予以治疗。

 

I believe we should treat everybody, and we should treat everybody regardless of fibrosis stage, co-infection status, and luckily this is possible in Germany from the beginning so we have no restrictions. The only restrictions to chronic Hepatitis C, as I mentioned, is HCV RNA detection six months apart, but there's no restriction in respect to transaminases and fibrosis stage-and age as well. 

 

Of course, the question remains if we should treat an 80-85 year old person without any detectable signs of liver disease, if we need to treat them, but if there is a wish for treatment from the patient or the patient's family, there is the indication of treatment. 

 

This is, I think, very important, and most important at this point is that we will be able to get closer to the WHO report of possible extinction of Hepatitis C in parts of the world, then we need to treat especially from the medic subgroups such as PWID, patients that had IV drug use in the past or patients who were incarcerated in prison because there is a high transmission rate in those subgroups of patients.

 

《国际肝病》：DAA治疗失败患者接受DAA再治疗的疗效有所下降，原因是什么，应如何处理？

 

Hepatology Digest: Some patients failed to initial DAAs and responded not as well as naive patients when accepting DAA re-treatment. So what are the reasons for the decreasing efficacy of DAAs in DAA-experienced patients？How should you manage the DAA-experienced patients? 

 

Peterson教授：幸运的是，使用新药治疗而得不到治愈的患者数量很少。在本届会议上，我们发布了一些数据显示，1400例患者接受了治疗，符合方案分析的SVR率为96%。仔细分析一下，病毒学失败率为3.5%。并非所有病毒学失败患者都出现了耐药病毒。但只要在首轮DAA抗病毒治疗失败后，在开始二次治疗之前，我们都应该对这些患者进行耐药检测，特别是针对NS5A区的耐药相关变异，因为现在认为NS4A抑制剂可引发耐药。就二次治疗而言，我们可以选择不包括NS5A抑制剂的联合方案，或者在抗病毒治疗方案中加用第三类药物，延长治疗疗程，或加用利巴韦林。

 

Professor Petersen: Luckily, the remaining number of patients that are not being cured with those new medications is rather small. We have just published here some data at this meeting showing now 1400 patients on treatment. We have seen that per-protocol there is a 96% SVR rate. If you look at this, there's 3.5% of virologic failure. Not all of these virologic failures patients have resistant viruses. But whenever there is a first round of antiviral treatment with DAAs not successful, before the second approach we should have a resistance testing of those patients, and especially in the NS5A region, because it's believed right now that the NS5A inhibitor is driving resistance. The second approach either we are able to have a combination therapy without NS5A inhibitors or we add a third class of antiviral treatment or we prolong the treatment or add ribavirin to those patients. 

 

只要有可能，我们就要立即给予这些慢性丙型肝炎患者再治疗。基线时无需检测耐药，再治疗前需要进行耐药检测，当了解耐药情况后，选择能覆盖这些耐药变异的抗病毒方案进行治疗。

 

We'll retreat as soon as possible. When we see these resistances in those cases - we do not do baseline, but we do the resistance testing before re-treatment and we'll acknowledge this and follow it with a kind of scheme of antiviral therapies that include these resistant variants. 

 

*The above posting is sponsored by Gilead Sciences to support scientific and medical education, and with non-promotional intent. 

 

以上文章由Gilead Sciences赞助以支持科学及医学教育，且无推广意图。