丙肝DAA药物相互作用的管理

        随着多项直接作用抗病毒药物（DAA）治疗我国丙型肝炎患者的临床试验数据陆续公布，DAA走入我国临床、服务患者的日子也进入了倒计时阶段。在APASL2017召开之际，《国际肝病》特组织国内外肝病领域权威专家，交流国内外在丙型肝炎的疾病特征、治疗模式和未来发展的认识和经验。本期为您带来首都医科大学附属北京友谊医院贾继东教授与德国汉诺威医学院Michael Manns教授有关DAA与其他药物间相互作用的管理。

 

贾继东教授：中国肝炎防治基金会副理事长、国际肝病协会前主席、亚太肝病学会前主席、中华医学会肝病学分会前主任委员

Michael Manns教授：曾任德国胃肠病学学会主席、德国肝病学会主席，德国内科学会主席，2007年荣获欧洲肝脏研究学会（EASL）成就奖

        慢性丙型肝炎患者的常见共病

        Manns教授：在世界许多地区，特别是日本和欧洲，HCV感染人群正在老年化。以德国为例，许多感染发生于20世纪60到80年代，主要由于输血所致。直至20世纪90年代开始进行血库筛查，才中止了通过输血或血制品所致的新发感染。这些患者目前年龄在六七十岁以上，往往因为合并其他疾病而需要同时应用降胆固醇、降压、降糖以及抗心律失常等药物。

        In some areas of the world, particularly Japan and Europe, the hepatitis C population is ageing. In Germany, for example, many of the infections occurred in the 1960s,70s and 80s through blood transfusions, until de novo infections via blood and blood products were stopped in 1990 due to blood bank screening. These patients are now in their 60s and 70s and more and have concomitant diseases requiring cholesterol lowering drugs, antihypertensive drugs, antidiabetic drugs and drugs for arrhythmias.

        贾教授：在中国HCV传播的途径过去主要为输血，但现在也有其他新的可能的途径。与西方国家相似，中国的HCV感染患者人群也开始老龄化。不过中国老年患者的比例总体上没有西方国家那么高，年龄峰值为40-60岁。同样地，老年患者合并糖尿病、高血压和肾脏疾病是常见问题。

        In China, the major route of HCV transmission was blood transfusion, but there are now other transmission routes. Similar to the Western countries, patients are also aging. In general though, our patients are not as old as those in Western countries - 40-60 years of age is the peak. And our older patients are fewer than in the West. But similarly, older patients with diabetes, hypertension and renal disease are common..

        共病对丙肝抗病毒治疗疗效的影响

        贾继东教授：在应用聚乙二醇干扰素和利巴韦林的时代，共病确实影响抗HCV的治疗效果。但在DAA清除HCV RNA方面，共病本身似乎并无实质性的不利影响--无论患者是否患有肝硬化、合并肾脏疾病等。在我看来这似乎不是一个大问题。

        In the era of peg-interferon and ribavirin, comorbidities did affect the efficacy of antiviral therapy for HCV. Now it seems that thecomorbitities themselves do not negatively affect the efficacy of DAAs in HCV RNA clearance, whether the patient has cirrhosis or renal disease or other comorbidities. It does not seem to be a big issue.

        然而，在中国应用DAA时必须注意一个问题，即同时应用中药--中药在中国应用得十分广泛，而安全性数据不完善。我们不知道当应用DAA的患者同时应用中药时可能会发生什么情况。并且想在网络或其他数据库中进行相关检索也非常困难（甚至可能无法实现）。因此这可能会是一个潜在的隐患。

        I must say, in China, one issue for the use of DAAs is concurrent use of herbal medicine, which is widely used and the safety data is not often available. We do not know what would happen if aherbal medicine is used together with the DAAs. It is also difficult, if not impossible, to check against online or other resources. This is a potential issue for Chinese patients where they are using DAAs as well as herbal medicine.

        DAA药物相互作用的管理

        Manns教授：DAA与其他药物DDI不像过去那么难以处理了。现有三类DAA：聚合酶抑制剂、NS5A抑制剂和蛋白酶抑制剂。一般而言，蛋白酶抑制剂的DDI问题最大，因为其通过细胞色素P450 3A4代谢，而这是很多其他药物（包括治疗高血压、高胆固醇血症的药物）的共同代谢途径。

        DDI is not as difficult as it was previously. There are the three classes of DAAs - the polymerase inhibitors, the NS5A inhibitors and the protease inhibitors. In general, the protease inhibitors have the biggest problems with DDIs because they are metabolized by cytochrome p450 3A4, like many of the other drugs we use for treating hypertension and cholesterol, for example.

        此时我们可以考虑其他类药物。另外，有时这不仅仅是一个类效应，我们可能还需要针对具体情况选择具体的某一个药物。就像贾教授提到的，我们可以应用利物浦大学网站来进行参考。这是一个非常好的网站，我们可以查找特定药物潜在的DDI。

        However, we can choose between these classes. Sometimes it is not only a class effect and we have to specifically look at the particular drug and, as Professor Jia mentioned, we can use the wonderful website from Liverpool University, which we all refer to. Once we know the specific drugs, we can look up the potential interactions.

        此外，我们面对的不仅是高龄患者以及需要治疗高血压和心律失常的患者，我们还会遇到合并HIV感染、接受抗HIV药物治疗的患者以及器官移植后应用免疫抑制治疗药物的患者，对于这些病例，我们也必须考虑他们应用的DAA以及同时应用的特定药物。

        In addition, we are not only dealing with an ageing population and treating hypertension and arrhythmias, we also have patients who are co-infected with HIV and using HIV drugs, as well as transplant patients who are using immunosuppressive drugs. So in these cases as well, we have to look at the DAA that is given and what specific co-medication the patient is using.

        通常，如果两种药物的代谢途径相同，那么一种药物的暴露量增加时，另外一种药物的暴露量则会减少。当药物的暴露量增加时是否会产生潜在毒性，我们必须进行评估。

        In general, if you have two drugs and they have the same route of metabolism, if exposure to one of the drugs is increased, for example, the exposure to the other drug is decreased. We have to assess if a potential toxicity can occur by increasing exposure to one or more drug.

        贾教授：中国还没有DAA上市，所以我们的经验还很少，但我们可以遵循指南。我们需要清楚理解不同DAA的代谢途径，知道患者患有哪些其他疾病以及正在应用哪些药物。我们可以查找利物浦大学网站，了解DAA与其他许多药物的DDI情况。但是，再次强调，对于服用中药的中国患者，应该十分小心与DAA的相互作用问题，目前可用的数据非常少。

        DAAs are not available right now in China, so we have little experience. Butwe can follow the guidelines and we need to clearly understand the metabolic pathways of the different DAAs. We need to know what other diseases patients are dealing with and what medications they are using.

        For that information, we can check the Liverpool website to see how the DAAs and many other medications will interact. But I wouldsay again, that Chinese patients who take herbal medicine should be very careful with DAAs because there is very little data available.

        Manns教授：最近报告，核苷类聚合酶抑制剂索磷布韦和一种抗心律失常药物之间可能发生特定的药物相互作用，但这是非常特殊的情况。除此之外，这个药物与其他药物发生DDI的情况非常少见。在应用蛋白酶抑制剂时，必须考虑其他药物是否通过细胞色素P450 3A4代谢的问题。但是通常情况下，我们总是可以选择其他药物的。现今有三类不同的DAAs可用，还有多种不同的联合治疗方案，与过去相比，DAA的药物相互作用问题变得容易多了，我们可以轻松管理患者。

        Very recently, there was a specific drug-drug interaction between the nucleoside polymerase inhibitor, sofosbuvir, and an anti-arrhythmic drug, but this was a very particular situation, and otherwise there are very few drug-drug interactions with that DAA. With the protease inhibitors, we have to consider the cytochrome P450 3A4 metabolism. But in general, we always have possibilities for alternatives, and if we are aware of this, we can easily manage the patient. Nowadays, with the various possibilities and the three different classes of drugs and various combinations, this is less of a problem than before.

        The above posting is sponsored by Gilead Sciences to support scientific and medical education, and with non-promotional intent.  The content was not reviewed prior to publication by Gilead Sciences.”
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