Jaeckel E, Manns M P
Abt. Gastroenterologie und Hepatologie, Medizinische Hochschule Hannover.
Z Gastroenterol. 2000 May;38(5):387-95. doi: 10.1055/s-2000-14882.
Due to the large number of patients chronically infected with hepatitis C virus and not responding to combination therapy with interferon-alfa 2 and ribavirin new therapeutic regimens are required. Early treatment of the viral infection might improve the response, as seen in treatment of HIV infection, thereby preventing progression to chronicity. The article reviews the natural course of an acute HCV infection after different modes of transmission like i.v.-drug abuse, transfusion, needle stick injury and blood products. As there are no good animal models for HCV infection, models of an acute infection with other noncytopathic viruses might improve our understanding of the mechanisms of viral clearance. Results from an acute infection of mice with the lymphocytic chorionmeningitis virus are demonstrating the development of a T-cell tolerance by anergy or deletion of virus specific T-cells as possible mechanisms for the failure of the immune system to clear the virus. These findings are compared to the results of CD4+ and CD8+ T-cell responses in patients with acute HCV infection. Several clinical trials have demonstrated a benefit of an early treatment of HCV infection. Although the natural course of acute HCV is changing during the last few years, even recent trials indicate that progression to chronicity might be prevented by early therapy. The studies show that therapy could be improved by daily dosing, higher single doses of interferon compared and prolongation of therapy up to six month. As most patients with acute HCV infection are rather seen in an outpatient practise than in hospitals cases of acute infections should be collected and treatment protocols be standardized to confirm these results in prospective trials. First results in 21 patients show that viral clearance under therapy was achievable in all of the patients.
由于大量丙型肝炎病毒慢性感染患者对干扰素-α2和利巴韦林联合治疗无反应，因此需要新的治疗方案。正如在HIV感染治疗中所见，病毒感染的早期治疗可能会改善反应，从而预防疾病进展为慢性。本文回顾了静脉药物滥用、输血、针刺伤和血液制品等不同传播方式后急性丙型肝炎病毒感染的自然病程。由于丙型肝炎病毒感染没有良好的动物模型，其他非细胞病变病毒急性感染的模型可能会增进我们对病毒清除机制的理解。淋巴细胞性脉络丛脑膜炎病毒急性感染小鼠的结果表明，通过无反应性或病毒特异性T细胞的缺失形成T细胞耐受性，这可能是免疫系统无法清除病毒的机制。将这些发现与急性丙型肝炎病毒感染患者的CD4+和CD8+ T细胞反应结果进行了比较。多项临床试验已证明早期治疗丙型肝炎病毒感染有益。尽管急性丙型肝炎的自然病程在过去几年中有所变化，但即使是最近的试验也表明，早期治疗可能预防疾病进展为慢性。研究表明，通过每日给药、增加干扰素单次剂量以及将治疗延长至6个月，可以改善治疗效果。由于大多数急性丙型肝炎病毒感染患者是在门诊而非医院就诊，因此应收集急性感染病例并标准化治疗方案，以便在前瞻性试验中证实这些结果。21例患者的初步结果显示，所有患者在治疗下均可实现病毒清除。
