Stratified Medicine to Optimise Treatment for Hepatitis C Virus Infection

分层医学是一种个性化医学，其中治疗专门针对最有可能对其作出反应的人，通常使用有关个人的详细信息。我们相信，丙型肝炎病毒（HCV）患者的治疗将从这种方法中受益匪浅。英国约有30万人感染了丙型肝炎病毒，其中只有一半被诊断为携带病毒。由于人体的免疫系统通常无法清除感染，这种病毒很有可能持续存在。丙型肝炎病毒感染肝脏，导致肝硬化（疤痕）、肝功能衰竭和肝癌。丙型肝炎病毒以不同的基因形式存在，称为基因型。在英国，大多数感染是由基因1型或基因3型引起的，它们发生的频率大致相同。丙型肝炎的治疗包括两种药物干扰素和利巴韦林。大约有一半接受治疗的患者对感染有反应并成功治愈。直到最近，还没有其他药物可用于治疗那些治疗失败的患者。预计在未来20年里，因丙型肝炎病毒而患上严重肝病的人数将继续上升。那些出现肝功能衰竭的人可以接受移植手术，但移植的器官很快就会被病毒感染，通常在几年内就会发病。直接对病毒起作用的新药（称为DAAs）于2012年首次在临床中与干扰素和利巴韦林联合用于NHS患者。DAA药物将治愈率提高到70%。然而，也有缺点：药物非常昂贵，每个病人的费用超过2万英镑；病毒可能对新药产生耐药性，使它们失效，并增加社区中耐药菌株的频率；第一波新药对基因1型有效，对基因3型无效；新药物可能会产生额外的副作用，因此可能在病毒被消灭之前就停止治疗。我们已经建立了一个丙型肝炎患者临床护理专家小组，他们将与丙型肝炎科学家合作，并与工业界合作。以这种方式结合专业知识应该有利于患者。该组织已经很好地合作，从英国各地的1万人那里收集血液样本和信息，并将其存入一个生物银行，由政府基础设施提供支持。我们的目标是评估病毒和感染者的基因组成。我们还将研究免疫系统对病毒的反应方式，并测量血液中的蛋白质标记物。我们会对正在接受治疗的患者以及患有严重肝病的患者进行评估，以便提前确定哪些患者会出现进一步的疾病并发症。我们团队的一个独特之处在于，我们有能力将所有这些因素结合在一起。我们将开发新技术，以便迅速获得数千名感染者的宿主和病毒序列。通过这种方式，我们希望改善患者的治疗选择，以便为最有可能从中受益的患者提供正确的治疗方法。我们将把重点放在HCV基因3型上，这是英国患者的一个特殊问题，同时也会关注那些更严重的肝病患者，这些患者更难以用新疗法治疗。最终，我们希望预测个体治疗反应的可能性，并可能通过我们的研究开发新的治疗方法。这将为NHS节省大量的成本，并意味着将药物提供给最有可能对药物产生反应的丙型肝炎病毒感染者。

Stratified Medicine is a type of personalised medicine where treatments are directed specifically at people who are most likely to respond to them, often using detailed information about individuals. We believe that the treatment of patients with hepatitis C virus (HCV) would benefit enormously from this approach. About 300,000 people in the UK are infected with HCV, only half of whom have been diagnosed as carrying the virus. The virus has a high tendency to persist as the body's immune system is usually unable to clear infection. HCV infects the liver, causing liver cirrhosis (scarring), liver failure and liver cancer. HCV exists in different genetic forms called genotypes. In the UK, most infections are caused by either genotype 1 or 3, which occur at about equal frequency. Treatment for HCV has consisted of two drugs interferon and ribavirin. Approximately half of patients receiving treatment respond and are successfully cured of infection. Until recently, no additional drugs were available to treat those who failed treatment. The number of people who develop severe liver disease from HCV is expected to continue to rise over the next two decades. Those who develop liver failure can be given a transplant but the transplanted organ is rapidly infected with the virus and often becomes diseased within a few years.New drugs, which directly act against the virus (called DAAs), are being used in combination with interferon and ribavirin in NHS patients for the first time in the clinic in 2012. DAA drugs increase the cure rate to 70%. However, there are drawbacks: the drugs are very expensive costing in excess of £20,000 per patient; the virus can become resistant to new drugs, rendering them useless and increasing the frequency of resistant strains in the community; the first wave of new drugs are effective against genotype 1 but not genotype 3 strains; additional side effects can be associated with the new drugs, so that treatment may be stopped before the virus is eliminated.We have developed a team of experts in the clinical care of HCV patients, who will work with HCV scientists, in partnership with industry. Combining expertise in this way should serve to benefit patients. The group is already working well together collecting blood samples and information from 10,000 people across the UK into a single bio-bank, supported by government infrastructure. We aim to assess the genetic make up of both the virus and the infected person. We will also look at the way in which the immune system responds to the virus, and measure protein markers in the blood. We will assess these in patients receiving therapy and also in those with serious liver disease to try to work out in advance who will develop further complications of their disease. A unique feature of our group will be the ability to draw all these strands together. We will develop new technologies so that we rapidly obtain the host and viral sequence in thousands of infected people. In this way we hope to improve treatment options for patients so that the right therapies are given to patients who are most likely to benefit from them. We will focus our efforts especially on HCV genotype 3, which is a particular problem in UK patients, and also on patients with more serious liver disease, who are more difficult to treat with the new therapies. Ultimately we hope to predict the likelihood of treatment response in individuals, and possibly through our investigations develop new therapies. This could bring considerable cost-savings to the NHS and means that drugs are given to HCV-infected people who are most likely to respond to them.