在中华医学会感染病学分会第十五次全国会议上，Clinical Infectious Disease杂志主编，来自美国加利福尼亚大学圣地亚哥分校的Robert T. Schooley教授发表了“HCV Elimination：focus shifting from patients to populations”专题演讲。会后，Schooley欣然接受《国际肝病》采访，解释“patients”（患者）层面与“populations”（人群）层面清除HCV的意义和区别。

 

Hepatology Digest: We have a goal proposed by WHO that of elimination of virus hepatitis including HCV infection by 2030. With the extensive application of DAAs, reaching this target is becoming possible. According to your presentation, could you please briefly introduce the clinical benefits of the elimination of HCV?

 

Dr Schooley: We have seen over the last few years that the deaths from hepatitis have increased to the point that more people are dying from hepatitis than HIV or malaria or tuberculosis around the world. So it is essential that we focus on the two viruses that are causing so many deaths and morbidity. In the case of HCV, we are fortunate as HCV can be cured in almost everyone who is treated with drugs that are very easy to take. Using these drugs, if we focus on those people who are infected with HCV, they can be cured, and just as importantly, will not be able to transmit the virus to other people. So in addition to curing people of the virus that is causing this mortality, we will begin to see it being eliminated from the population and new cases will not be occurring that require treatment.

 

《国际肝病》：WHO提出到2030年实现完全消除包含HCV在内的病毒性肝炎，随着DAAs的广泛应用，这一目标也逐渐成为可能。结合您的演讲内容，请您简要概述下清除HCV能够带来的临床获益？

 

Schooley教授：我们看到，在过去几年里全球肝炎导致的死亡数量已经超过了HIV或疟疾或结核病导致的死亡数量。因此，对于造成如此之多的死亡人数和患病人数的这两种病毒，我们必须加以关注。对于HCV，我们很幸运，因为使用一些很容易服用的药物治疗，几乎所有人就都可以治愈，而且同样重要的是，这些感染HCV的人在治愈后不会再把病毒传播给其他人。因此，对于这种引起大量死亡病例的病毒，我们除了能够治愈感染病毒的个体，还将看到从人群中将之清除，不会再有需要治疗的新病例出现。

 

Hepatology Digest:  In the DAAs era, in your opinion, what obstacles should be conquered to get the population-based elimination of HCV? You told us "shifting the focus from patients to populations. What are the main differences between “patients” and "populations"？

 

Dr Schooley: Up until now, we have been treating people who have the most severe liver disease. That was important because they were the ones who were most likely to develop liver failure and liver cancer in the short-term. It was medically urgent to get them treated. For the most part, those people have been infected for years and are not doing much virus transmission any more. The people transmitting the virus are mostly those who are younger, more sexually active, perhaps sharing needles, and who don’t yet have a lot of liver disease. They have not been targeted as much for treatment as those who have liver disease. If we want to eliminate the virus from the population, at the same time as we treat people who need it for their own medical health, we need to think about the health of the whole population. That involves treating the virus in people who are contributing most to the spread of the virus to other individuals.

 

《国际肝病》：在DAAs治疗时代，您认为要实现基于人群的HCV清除还需要克服那些困难？从“patients”（患者）到“population”（人群）的区别在哪里？

 

Schooley教授：直到现在为止，我们一直治疗的都是那些肝脏疾病最严重的患者。这一点很重要，因为他们是最有可能在短期内发展为肝功能衰竭和肝癌的人。对他们进行治疗是非常紧急的。最重要的是，这些人已经被感染了多年，不会再有大量的病毒传播。传播病毒的人大多是年轻的、性活跃的、可能共享针头的人，以及肝病不太严重的人。就治疗的目标人群而言，我们更在意那些有肝病的人，这部分人相对不那么迫切。 如果我们想从人群中消除病毒，同时当我们治疗那些从自身健康出发有医疗需求的人时，我们需要考虑全民的健康。这就涉及治疗那些对病毒传播“贡献”最大的个体。

 

Hepatology Digest: Will DAAs completely replace the previous therapy that is the combination of PegIFN and RBV? Is it still clinically valuable to explore the research the combination application of PegIFN、RBV and DAAs？

 

Dr Schooley: I think the DAAs are so effective and so well tolerated, that there is no role for interferon or ribavirin. They should be put to bed and no longer used for hepatitis C.

 

《国际肝病》：DAAs是否会完全取代既往的PegIFN联合RBV的治疗方案，探索PegIFN、RBV及DAAs之间的联合应用是否还有临床价值？

 

Schooley教授：我想DAA非常有效、耐受性也非常好，现在干扰素或利巴韦林不再有用武之地，它们将不再用于丙型肝炎的治疗。

 

Hepatology Digest: Although DAAs has showed satisfactory effects and safety, a small number of reports mentioned that there have been some DAAs resistance cases. Will DAAs resistance have influence on treatment for the population with chronic HCV infection? If so, what is the clinical reaction?

 

Dr Schooley: Luckily, we have so many different classes of HCV drugs, that when we have patients who fail therapy and have a drug resistant virus, they can be successfully retreated with a different combination of drugs. So unlike the situation with HBV, where we have a lot of people who are very difficult to treat due to drug resistance, for HCV, by using the right combination of drugs and doing sequencing once we understand the resistance pathways in people with a resistant virus, we can find a regimen that will cure almost anyone.

 

《国际肝病》：虽然DAAs显示出了较为良好的疗效及安全性，但是也有少量报道显示，临床上已有对DAAs耐药的情况，耐药是否会影响针对人群的HCV治疗，临床上如何应对这种情况？

 

Schooley教授：幸运的是，我们有多种不同种类的抗HCV药物。当有患者治疗失败并且出现了耐药病毒时，通过使用不同的药物组合，他们可以成功地再治疗。因此，与HBV感染时的情况不同--有很多乙肝患者由于发生耐药而很难治疗，对于HCV感染，通过使用正确的药物组合和测序，只要我们了解耐药病毒的耐药途径，我们能够找到可治愈几乎任何人的方案。

 

Hepatology Digest: HCV and HIV co-infection is very common. What is the meaning of DAAs treatment for these special patients?

 

Dr Schooley: HIV/HCV infected people is a population that we target very early on for treatment in the United States. There are two reasons for that. The first reason is that the hepatitis C infection is more rapidly progressive in this population than in people who don’t have an HIV co-infection. There is a greater medical need for treatment. We have treated a larger fraction of the HIV/HCV co-infected population in the US than those with HCV alone. The other reason is that the HIV/HCV co-infected population is probably transmitting the virus more rapidly than those who have HCV alone. So for both personal health and for population clearance of the virus, focusing on this key population is very important in terms of treatment priorities.

 

《国际肝病》：HCV/HIV是临床十分常见的合并感染，DAAs药物在治疗此类特殊患者中的意义如何？

 

Schooley教授：在美国，HIV/HCV共感染患者很早就被列入治疗目标人群。 有两个原因。 第一个原因是，在这个人群中丙型肝炎感染比没有合并感染HIV的患者进展更迅速，他们对治疗有更大的医疗需求。在美国，HIV/HCV 共感染人群中接受治疗的比例高于单纯 HCV感染的人群。另一个原因是 HIV/HCV 共感染患者可能比单独感染 HCV 的人更快速地传播病毒。因此，在个人健康和病毒的人群清除两个层面，注意这一关键群体的治疗优先性是非常重要的。