在第52届欧洲肝脏研究学会（EASL）年会（ILC2017）上，丙型肝炎的“消除”和综合管理延续了近年来的热度，继续受到关注。为帮助中国肝病医生全方位了解直接作用抗病毒药物（DAA）时代丙型肝炎的管理，《国际肝病》再次组织国内外权威专家进行巅峰对话，分享他们的真知灼见和宝贵经验。本期为您带来德国汉诺威医学院Michael Manns教授介绍欧洲的丙型肝炎筛查模式和治疗人群的选择。

 

《国际肝病》:大家都在说“消除”丙肝。发现患者是治愈患者的前提，所以筛查非常重要。但是我们无法对每一个人进行筛查，对于筛查对象和项目的开展，欧洲是怎样运作的？

 

Manns教授：欧洲也提出了消除丙型肝炎感染的目标，并且于一年前联名签署了消除丙型肝炎的宣言（注：2016年EASL年会时，EASL、AASLD、APASL和ALEH以及WHO五大组织领导人共同签署了消灭肝炎的联合宣言）。

 

不过，在欧洲并没有开展普遍筛查。有经济学评价表明，只有当人群中（丙型肝炎感染）的流行率至少达到4.8%时，普遍筛查才具有成本效益。

 

我们也有一些推荐--包括欧洲以及一些国家的指南中都有相关内容，即我们应该对ALT升高的人群进行（丙型肝炎）筛查。例如，德国肝脏基金会--我有幸担任这个基金会的主席--努力将ALT检测纳入一个被称为Checkout 35的检查项目，年龄超过35岁后这个检查项目将由保险公司支付费用。如果患者ALT升高，那么必须进行后续的诊断，其中包括丙型肝炎病毒抗体检测。

 

此外凡是在1990年之前有过输血史、或既往曾有静脉吸毒史的人，以及所有的医务工作者都应该检测ALT和丙型肝炎病毒抗体。

 

Hepatology Digest: We are seeking the “elimination” of hepatitis C, but only when the patients are found can they then be possibly cured, so the screening is very important. However, we are not able to screen everyone. Could you please talk about the screening and testing program of hepatitis C in Europe?

 

Prof. Manns: There's also a goal of eliminating Hepatitis C infection in Europe. There has been a signature of a manifesto against Hepatitis C already more than one year ago. Nevertheless, we do not have universal screening programs in Europe. There are also economic evaluations that show that only when there is a prevalence of at least 4.8 percent in the population universal screening is cost effective. 

 

Nevertheless, there are recommendations that this is part of several guidelines-the European ones and some national guidelines-that we should test for elevated ALT. And, for example, the German Liver Foundation-which I have the privilege to be the president of the German Liver Foundation-we fight for enrolling ALT-testing in a so-called Checkup 35, which is a checkup being paid by insurance companies from the age of 35. And there, if the patient has elevated ALT, then there has to be a following diagnostic procedure including Hepatitis C antibody testing. 

 

Furthermore, everybody who has had blood transfusions before 1990, everybody who has had a history of IV drug abuse, all healthcare workers should be tested for ALT and Hepatitis C antibodies. 

 

《国际肝病》:通过筛查发现患者后如何保证这些患者能得到及时有效的治疗，请您介绍一下欧洲的经验。

 

Manns教授：这是一个非常重要的问题。仅仅诊断疾病是不够的，你必须治疗。

 

欧洲的模式正在发生变化。欧洲的情况多种多样，既有批准药物的中枢机构EMA，同时也有非常重要的、在国家层面的医疗报销。有像德国这样国内有超过一百个不同的个人保险公司的国家，也有像葡萄牙这样由政府进行统一价格谈判的国家。因此必须采取不同的策略。

 

有些国家无论纤维化分期如何，对丙型肝炎进行普遍的国家医疗报销，而有些国家对活检和特定纤维化分期有要求。过去有治疗的优先级，首先治疗那些有严重肝纤维化、显著肝纤维化和肝硬化的患者。但在许多国家，接受治疗的肝硬化患者的数量在减少。因此当前的治疗开始外延到肝病程度较轻的患者。例如在德国和法国，对于患者是否处于显著肝纤维化阶段没有限制。然而我认为，这也存在一个容量问题，医疗系统是否能够治疗所有的患者。

 

我认为在未来，随着（药物）价格的持续下降，我们能够将治疗范围显著扩大，将纤维化程度不重的患者纳入进来。

 

Hepatology Digest：How can we ensure that patients getting treated in a timely and efficient way after they are diagnosed with hepatitis C? What's the European experience? 

 

Prof. Manns: That is a very important question. It is not enough to diagnose the disease; you have also to treat. And here is a changing paradigm in Europe. Europe is very heterogeneous; we have the EMA, the central European authority approving drugs, but nevertheless, reimbursement is very important. And reimbursement is organized at the national level. We have countries like Germany where you have more than a hundred different individual insurance companies, and you have countries like Portugal where the government is negotiating a universal price. So, the strategy has to be different. 

 

There are countries where there is universal reimbursement of Hepatitis C independent of fibrosis stage, and while other countries ask for a biopsy and a certain fibrosis stage. It has been a priority in the past to treat; first, those with advanced fibrosis, with significant fibrosis, with liver cirrhosis. But in many countries, the number of cirrhotic patients being treated has decreased. So now treatment is reaching out to patients with mild liver disease. In Germany, for example, as it is in France, there's no limitation, no restriction, to patients with significant fibrosis. However, I think, it's also a question of capacity-whether the healthcare system is able to treat all the patients. 

 

I think in the future, with the continuing decline in price, we will reach out with a therapy to those patients with less fibrosis, significantly.

 

《国际肝病》：在DAA已经上市的国家，有些人鼓励全面（广泛）治疗丙肝，还有的仍然坚持优先治疗特定人群。您持哪种观点，原因是什么？

 

Manns教授：有各种各样的原因。第一是经济原因。一些国家无法负担所有患者的治疗。然后是医疗系统，如果它能在几年内成倍扩张，才能承担得起治疗任务。还有医疗体系的容量问题，我们不可能在一年内治疗所有的丙型肝炎患者，你需要医生和护士来照顾患者。

 

我想，所有丙型肝炎患者迟早都将得到治疗。但首先，我们需要治疗那些肝病程度较重的患者，因为他们发生肝癌的风险较高。我们要减少对肝移植的需求，特别是在德国，这将有助于减轻对捐献器官短缺的压力。在我们治疗了所有的严重病患后，我们就可以将治疗扩大到那些无症状的丙肝携带者。

 

我们知道，如果能够治愈丙型肝炎，不仅将降低肝脏相关死亡率，还可减少非肝脏相关死亡率。在这一点上，我们必须做更多的研究，以获得更多数据来强调这个效果。

 

Hepatology Digest: In countries where DAAs are available, some encourage universal treatment for Hepatitis C, while others favor prioritized treatment for special patients group, for example, patients with advanced diseases. So, which side would you support and what are the reasons?

 

Prof. Manns: There are various reasons. Number one is economic reason. Some countries cannot afford to treat everybody. And then the healthcare system-they are able to afford treatment if it's split over several years. And then there is the capacity of the healthcare system. You cannot treat all Hepatitis C patients in one year. You also need physicians, nurses to take care of the patients. 

 

I think sooner or later, all patients with Hepatitis C will be treated. But first of all, we need to treat those with advanced disease as they have higher risk of developing liver cancer. We want to reduce indications for liver transplantation. In particular, in Germany, this would help to decrease the shortage in donor organs. And then, once we have treated all of the severe cases, then we can extend treatment to those patients who are just asymptomatic carriers. 

 

And we know that if we cure Hepatitis C, that this does not only reduce liver-related mortality, it reduces also non-liver related mortality. Here, we have to do more research in order to get more data to underline this phenomenon. 

 

The above posting is sponsored by Gilead Sciences to support scientific and medical education, and with non-promotional intent. The content was reviewed prior to publication by Gilead Sciences. 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。文章内容发布前已经过Gilead Sciences审阅。