KFO 129: Mechanisms for Development of Resistance and Optimisation of Antiviral Strategies of Hepatitis C Virus Infection Comprising Integrative Biomathematical and Bioinformatical Models

KFO 129：丙型肝炎病毒感染的耐药性发展机制和抗病毒策略优化，包括综合生物数学和生物信息模型

• 批准号: 5397647
• 金额: --
• 依托单位: Institut für Biostatistik und mathematische Modellierung
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5397647?language=en
• 关键词: KFO; 129; Mechanisms; Development; Resistance

This Clinical Research Unit comprises research projects from different disciplines including clinical medicine, biomathematics, bioinformatics, structural biology, immunology, virology, and pharmaceutical chemistry to characterise resistance to hepatitis C therapy and to develop new treatments approaches. Inflammation of the liver caused by chronic infection with the hepatitis C virus (HCV) affects more than 170 million patients throughout the world including 500,000 to 800,000 patients in Germany. After many years of infection chronic hepatitis C can proceed to severe liver diseases. Unfortunately, sustained virologic response rates to currently available anti-HCV treatments are only about 50 to 60 percent. Many new drugs, especially inhibitors of the HCV NS3 serine protease and the RNA-dependent RNA polymerase, are currently under preclinical and early clinical evaluation. Therefore models for predicting treatment response are highly desirable. Additionally, efficient and reliable prediction algorithms of treatment response early after initiation of therapy may lead to individualised optimisation of treatment schedules in clinical practise.

该临床研究部门包括来自不同学科的研究项目，包括临床医学，生物数学，生物信息学，结构生物学，免疫学，病毒学和药物化学，以消除对丙型肝炎治疗的耐药性并开发新的治疗方法。由丙型肝炎病毒（HCV）慢性感染引起的肝脏炎症影响全世界超过1.7亿患者，包括德国的50万至80万患者。经过多年的感染，慢性丙型肝炎可以发展为严重的肝脏疾病。不幸的是，目前可用的抗HCV治疗的持续病毒学应答率仅为约50%至60%。许多新药，特别是HCV NS3丝氨酸蛋白酶和RNA依赖性RNA聚合酶的抑制剂，目前正在进行临床前和早期临床评价。因此，用于预测治疗反应的模型是高度期望的。此外，在治疗开始后早期有效和可靠的治疗反应预测算法可能导致临床实践中治疗方案的个性化优化。

项目成果

Clinical significance of in vitro replication-enhancing mutations of the hepatitis C virus (HCV) replicon in patients with chronic HCV infection.

• DOI: 10.1086/497142
• 发表时间: 2005-11
• 期刊: The Journal of infectious diseases
• 作者: C. Sarrazin;U. Mihm;E. Herrmann;C. Welsch;M. Albrecht;U. Sarrazin;S. Traver;Thomas Lengauer;S. Zeuzem

Clinical relevance of the 2'-5'-oligoadenylate synthetase/RNase L system for treatment response in chronic hepatitis C.

• DOI: 10.1016/j.jhep.2008.08.024
• 发表时间: 2009-01
• 期刊: Journal of hepatology
• 影响因子: 25.7
• 作者: U. Mihm;Oliver Ackermann;C. Welsch;E. Herrmann;W. Hofmann;N. Grigorian;M. Welker;Thomas Lengauer;S. Zeuzem;C. Sarrazin

Role of nucleoside transporters SLC28A2/3 and SLC29A1/2 genetics in ribavirin therapy: protection against anemia in patients with chronic hepatitis C

• DOI: 10.1097/fpc.0b013e32834412e7
• 发表时间: 2011-05-01
• 期刊: PHARMACOGENETICS AND GENOMICS
• 影响因子: 2.6
• 作者: Doehring, Alexandra;Hofmann, Wolf Peter;Loetsch, Joern
• 通讯作者: Loetsch, Joern

Somatic hypermutation and mRNA expression levels of the BCL‐6 gene in patients with hepatitis C virus‐associated lymphoproliferative diseases *

丙型肝炎病毒相关淋巴增殖性疾病患者 BCLâ6 基因的体细胞超突变和 mRNA 表达水平*

• DOI: 10.1111/j.1365-2893.2006.00833.x
• 发表时间: 2007
• 期刊: Journal of Viral Hepatitis
• 影响因子: 2.5
• 作者: W.P. Hofmann;B. Fernandez;E. Herrmann;C. Welsch;U. Mihm;B. Kronenberger;S. Zeuzem;C. Sarrazin
• 通讯作者: C. Sarrazin

Structural and functional comparison of the non-structural protein 4B in flaviviridae.

黄病毒科非结构蛋白4B的结构和功能比较

• DOI: 10.1016/j.jmgm.2007.03.012
• 发表时间: 2007
• 期刊: Journal of molecular graphics & modelling
• 影响因子: 2.9
• 作者: C. Welsch;M. Albrecht;E. Herrmann;M.W. Welker;C. Sarrazin;A. Scheidig;T. Lengauer;S. Zeuzem
• 通讯作者: S. Zeuzem