Different clinical behaviors of acute hepatitis C virus infection are associated with different vigor of the anti-viral cell-mediated immune response.

Abstract

The anti-viral T cell response is believed to play a central role in the pathogenesis of hepatitis C virus infection. Since chronic evolution occurs in Ͼ 50% of HCV infections, the sequential analysis of the T cell response from the early clinical stages of disease may contribute to define the features of the T cell response associated with recovery or chronic viral persistence. For this purpose, 21 subjects with acute hepatitis C virus infection were sequentially followed for an average time of 44 wk. Twelve patients normalized transaminase values that remained normal throughout the follow-up period; all but two cleared hepatitis C virus-RNA from serum. The remaining nine patients showed persistent viremia and elevated transaminases. Analysis of the peripheral blood T cell proliferative response to core, E1, E2, NS3, NS4, and NS5 recombinant antigens and synthetic peptides showed that responses to all hepatitis C virus antigens, except E1, were significantly more vigorous and more frequently detectable in patients who normalized transaminase levels than in those who did not. By sequential evaluation of the T cell response, a difference between the two groups of patients was already detectable at the very early stages of acute infection and then maintained throughout the followup period. The results suggest that the vigor of the T cell response during the early stages of infection may be a critical determinant of disease resolution and control of infection. ( J. Clin. Invest. 1996. 98:706-714.)

Cellular immune responses against hepatitis C virus: the evidence base 2002

“…Although these do appear to be targeted, this is not exclusive and responses to other gene products are also seen [17]. The strength of the CD8 + T cell response against one epitope when measured using a tetramer, may be up to 8% of the total CD8 + T cells, and can include responses to at least 8 separate epitopes [10].…”

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

“…While HCV is spontaneously cleared with a vigorous and broad virus-specific effector T-cell response, such responses are impaired in persistent infections (1)(2)(3)(4)(5). While most studies have focused on the antiviral effector cytokine IFNγ, a role for the immune regulatory cytokine interleukin-10 (IL-10) has been suggested by enhanced HCV titers and reduced hepatic fibrosis during exogenous IL-10 therapy in HCV-infected patients (6) as well as associations between IL-10 promoter polymorphisms and clinical outcomes (7,8).…”

Factors influencing a low rate of hepatitis C viral RNA clearance in heroin users from Southern China

“…Natural history studies have found that 15%-59% of people who are infected with HCV will undergo spontaneous viral clearance with no further liver disease due to HCV [3][4][5][6][7][8][9][10][11] . The remaining will develop chronic HCV infection that can lead to cirrhosis, hepatocellular carcinoma and the need for a liver transplant.The exact mechanism of HCV RNA clearance is not well understood although recent studies have shown that clearance is associated with strong, broad cellular immune responses [12][13][14][15][16][17][18][19] . Other factors such as younger age [3,20] , female gender [21,22] , presence of hepatitis B surface antigen (HBsAg) [3,23] , certain HLA alleles [6,[24][25][26][27][28][29] , and low viral quasispecies diversity [30] have been linked to increased HCV RNA clearance.…”