Establishment of a Resource for Long-Term Study of Hepatitis C Virus Infection in the UK - HCV Research UK

在可预见的未来，与慢性丙型肝炎病毒（HCV）感染相关的临床问题将在英国继续增加。虽然在了解病毒的生物学和改善医疗保健方面已经取得了相当大的进展，但在英国，与HCV感染特征相关的许多问题仍未得到解决，例如导致严重肝脏疾病发展和治疗无效的因素。为了解决这些问题，该提案旨在创建允许招募至少10,000名患者的全国队列的基础设施。组建如此规模的队列是必要的，以产生具有代表性但足够多样化的患者特征和临床样本集合，以详细探索可能导致HCV发病机制和治疗反应的决定因素。将创建的国家资源的关键组成部分是保留患者特征细节的临床研究数据库，临床样本的生物库，将形成英国储存库，以及保存病毒和宿主遗传信息的序列和生物信息学数据库。基础设施将由国家机构（健康保护局和苏格兰健康保护局）、诺丁汉的胃肠病学和肝脏疾病生物医学研究单位以及格拉斯哥的MRC病毒学单位的现有知识和专业知识提供支持和建立。患者将从英国大部分为hcv感染患者提供护理的临床中心招募。为了为临床研究和序列数据库的实用性提供原理证明，并结合临床样本生物库的可用性，将进行一系列有限的研究项目。这些项目将侧重于检查患者遗传标记与治疗结果之间是否存在相关性。此外，还将确定不同种族的大量HCV基因型1和3分离株的病毒序列。这些研究将为序列和生物信息学数据库中的信息提供基础。这样一个结构良好的资源的可用性极有可能刺激英国对HCV感染进行更多的临床和基础研究，也将为大规模患者慢性感染自然史的纵向研究奠定基础。

Clinical problems associated with chronic infection by hepatitis C virus (HCV) will continueto increase in the UK for the foreseeable future. While there has been considerableprogress with understanding the biology of the virus and improvements in healthcareprovision, many issues relevant to the characteristics of HCV infection in the UK remainunresolved, such as the factors that contribute to development of serious liver diseaseand failure to respond to treatment. To address these issues, this proposal aims to createthe infrastructure that will allow recruitment of a national cohort of at least 10,000patients. Assembling a cohort of this size is necessary to generate a representative butsufficiently diverse collection of patient characteristics and clinical samples to explore indetail the determinants that may contribute to HCV pathogenesis and response totreatment. The key components of the national resource that will be created are a clinicalresearch database for retaining details of patient characteristics, a biobank of clinicalsamples, which will form a UK repository, and a sequence and bioinformatics database tohold viral and host genetic information. The infrastructure will be supported by and buildupon existing knowledge and expertise at national agencies (Health Protection Agencyand Health Protection Scotland), the Gastroenterology and Liver Disease BiomedicalResearch Unit at Nottingham and the MRC Virology Unit in Glasgow. Patients will berecruited from clinical centres across most of the UK who provide care for HCV-infectedpatients. To provide proof of principle for the utility of clinical research and sequencedatabases combined with the availability of a biobank of clinical samples, a limited seriesof research projects will be performed. The projects will focus on examining whetherthere is a correlation between patient genetic markers and treatment outcome. Inaddition, the viral sequences of a large number of isolates for HCV genotypes 1 and 3 indifferent ethnic groups will be determined. These studies will provide the foundation forthe information that will be deposited in the sequence and bioinformatics database. Theavailability of such a well-structured resource is highly likely to stimulate greater clinicaland fundamental research into HCV infection in the UK and will also form the basis forlongitudinal studies into the natural history of chronic infection in a large cohort ofpatients.