Guobuzaite Ausra, Chokshi Shilpa, Balciūniene Ligita, Voinic Alina, Stikleryte Ausra, Zagminas Kestutis, Ambrozaitis Arvydas, Naoumov Nikolai
Department of Infectious Diseases, Faculty of Medicine, Vilnius University,Vilnius, Lithuania.
Medicina (Kaunas). 2008;44(7):510-20.
Hepatitis C virus infection (HCV) has a high rate of chronic evolution; however, the underlying mechanisms remain to be elucidated. We investigated natural clinical, virological, and immunological course of acute HCV infection in order to identify possible prognostic factors of spontaneous resolution and to gain more understanding of early characteristics responsible for viral clearance or persistence.
Eight patients with acute symptomatic hepatitis C were prospectively followed up for more than 6 months (range, 8-14 months). None of the individuals received antiviral therapy during the study period. We analyzed biochemical, virological, and immunological parameters of these patients detected at different time-points of the follow-up. Plasma HCV RNA was quantitated using TaqMan real-time polymerase chain reaction. Virus-specific CD4(+) T cells were enumerated by interferon-gamma (IFN-gamma) ELISpot assay.
Two of eight individuals resolved HCV spontaneously, while the remaining patients developed chronic HCV infection. HCV RNA became undetectable within 14 days of the study, followed by a rapid alanine aminotransferase normalization in patients with resolved infection. On the contrary, chronically infected subjects demonstrated persistent viremia or intermittently undetectable HCV-RNA, accompanied by polyphasic alanine aminotransferase profile throughout the study. Patients with self-limited hepatitis C displayed the strongest virus-specific CD4(+) T (IFN-gamma) cell reactivity within the first weeks of the follow-up, while persistently infected subjects initially showed a weak antiviral CD4(+) T (IFN-gamma) cell response.
In most cases, acute hepatitis C progresses to chronic disease. Viral clearance within the first month after clinical presentation accompanied by monophasic alanine aminotransferase profile could predict recovery. Early and strong CD4(+)/Th1 immune response against HCV might play an important role in the disease resolution.
丙型肝炎病毒感染（HCV）慢性化进展率较高；然而，其潜在机制仍有待阐明。我们研究了急性HCV感染的自然临床、病毒学和免疫学进程，以确定自发清除的可能预后因素，并更深入了解导致病毒清除或持续存在的早期特征。
对8例急性症状性丙型肝炎患者进行了超过6个月（范围为8 - 14个月）的前瞻性随访。在研究期间，所有个体均未接受抗病毒治疗。我们分析了这些患者在随访不同时间点检测到的生化、病毒学和免疫学参数。使用TaqMan实时聚合酶链反应对血浆HCV RNA进行定量。通过干扰素-γ（IFN-γ）酶联免疫斑点试验计数病毒特异性CD4(+) T细胞。
8例个体中有2例自发清除了HCV，其余患者发展为慢性HCV感染。在研究的14天内，HCV RNA变得无法检测到，随后感染得到清除的患者丙氨酸氨基转移酶迅速恢复正常。相反，慢性感染的受试者表现出持续的病毒血症或间歇性无法检测到的HCV-RNA，在整个研究过程中丙氨酸氨基转移酶呈现多相变化。自限性丙型肝炎患者在随访的第一周内表现出最强的病毒特异性CD4(+) T（IFN-γ）细胞反应，而持续感染的受试者最初表现出较弱的抗病毒CD4(+) T（IFN-γ）细胞反应。
在大多数情况下，急性丙型肝炎会进展为慢性疾病。临床表现后第一个月内病毒清除并伴有单相丙氨酸氨基转移酶变化可预测康复。针对HCV的早期且强烈的CD4(+)/Th1免疫反应可能在疾病清除中起重要作用。
