Abstract
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.
Highlights
More than 170 million people worldwide are infected with the hepatitis C virus (HCV) [1, 2]
Acute hepatitis C progresses to chronic disease
And strong CD4+/Th1 immune response against HCV might play an important role in the disease resolution
Summary
More than 170 million people worldwide are infected with the hepatitis C virus (HCV) [1, 2]. 90% of newly infected patients develop chronic hepatitis [3, 4]. Viral clearance is associated with vigorous and permanently maintained T cell responses that target multiple HCV epitopes during acute infection. Patients developing chronic hepatitis C appear to display weak, narrowly focused, and often dysfunctional antiviral cell-mediated immunity. Interactions between the virus and the host immune response seem to be critical in determining outcome of the disease. In this respect, patients with acute HCV infection provide an ideal opportunity to understand the correlates for successful or failed immune response to hepatitis C virus
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