Pegylated interferon ␣ (PEG IFN-␣) improves sustained virological response rates in chronic hepatitis C, but neither its role in acute hepatitis C nor the biologic basis for its action has been defined. This prospective study assessed the efficacy of PEG IFN-␣ treatment in acute hepatitis C in relation to the kinetics of hepatitis C virus (HCV)-specific CD4 ؉ T cell responses during therapy and follow-up. Forty subjects with proven acute hepatitis C who received either PEG IFN-␣ plus ribavirin (n ‫؍‬ 20) or PEG IFN-␣ monotherapy (n ‫؍‬ 20) for 24 weeks in addition to 14 untreated subjects with acute hepatitis C were prospectively followed. Serum HCV RNA, HCV-specific CD4 ؉ T cell responses, and cytokine production were measured before and during therapy and at follow-up and correlated to the outcome. The sustained virological response rate was 85% with PEG IFN-␣/ribavirin combination and 80% with PEG IFN-␣ monotherapy. Five untreated subjects had spontaneous recovery. The frequency, magnitude, and breadth of HCV-specific CD4 ؉ T helper 1 responses were significantly higher in treated subjects compared with untreated subjects with self-limited disease or subjects with chronic evolution. The CD4 ؉ T cell responses were maintained in subjects with sustained virological responses and self-limited disease but fluctuated in those who developed chronic infection. In conclusion, PEG IFN-␣ therapy in acute hepatitis induces high rates of sustained virological response and prevents choronicity, probably through efficient early stimulation of multispecific HCV-specific CD4 ؉ T helper 1 responses.

Background: The response rates and duration of peginterferon alpha (PEG-IFN-a) and ribavirin combination therapy in chronic hepatitis C genotype 4, the prevalent genotype in the Middle East and Africa, are poorly documented. Aims: To compare the efficacy and safety of 24, 36, or 48 weeks of PEG-IFN-a-2b and ribavirin therapy in chronic hepatitis C genotype 4. Methods: In this prospective, randomised, double blind study, 287 patients with chronic hepatitis C genotype 4 were randomly assigned to PEG-IFN-a-2b (1.5 mg/kg) once weekly plus daily ribavirin (1000-1200 mg) for 24 weeks (group A, n = 95), 36 weeks (group B, n = 96), or 48 weeks (group C, n = 96) and followed for 48 weeks after completion of treatment. Early viral kinetics and histopathological evaluation of pre-and post treatment liver biopsies were performed. The primary end point was viral clearance 48 weeks after completion of treatment. Results: Sustained virological response was achieved in 29%, 66%, and 69% of patients treated with PEG-IFN-a-2b and ribavirin for 24, 36, and 48 weeks, respectively, by intention to treat analysis. No statistically significant difference in sustained virological response rates was detected between 36 and 48 weeks of therapy (p = 0.3). Subjects with sustained virological response showed greater antiviral efficacy (e) and rapid viral load decline from baseline to treatment week 4 compared with non-responders and improvement in liver histology. The incidence of adverse events was higher in the group treated for 48 weeks. Conclusion: PEG-IFN-a-2b and ribavirin for 36 or 48 weeks was more effective in the treatment of chronic hepatitis C genotype 4 than treatment for 24 weeks. Thirty six week therapy was well tolerated and produced sustained virological and histological response rates similar to the 48 week regimen.

Acute hepatitis C virus (HCV) is typically defined as new viremia and antibody seroconversion.Rates and immunologic correlates of hepatitis C clearance have therefore been based on clearance of viremia only in individuals who initially had an antibody response. We sought to characterize the immunological correlates of clearance in patients with acute hepatitis C and their sexual contacts. We prospectively determined CD4؉ and CD8؉ cytotoxic T-lymphocyte responses in index patients with acute HCV and their sexual contacts who developed acute infection, either with or without spontaneous clearance, as well as those contacts who never developed viremia. Responses were measured using proliferation and ELISpot assays for CD4؉ and CD8؉ responses. We demonstrate in this prospective study that cellular immune responses can develop in exposed but persistently aviremic and antibody-negative individuals as well as those individuals with spontaneous clearance of acute HCV. These findings lend further credence to the importance of cellular immune responses in recovery from HCV and suggest that low exposure to HCV may lead to development of HCV-specific immune responses without ongoing HCV replication. This finding has important implications for HCV vaccine and therapeutic development.Hepatitis C virus (HCV) is a frequent cause of liver disease, leading to chronic infection in as many as 170 million persons worldwide. Vaccine development for HCV, like that for human immunodeficiency virus type 1 (HIV-1), is limited by the quasispecies nature of the virus as well as a lack of clear evidence that humoral immune responses protect against infection. Unlike patients with HIV-1, some individuals infected with acute hepatitis C can recover, although the asymptomatic nature of acute infection in most infected persons and the relative difficulty in conducting prospective studies have limited our understanding of the correlates of recovery from infection. Therefore, most studies have relied upon retrospective identification of subjects who previously cleared HCV to ascertain the correlates of protective immunity. These studies have shown that vigorous polyclonal cellular immune responses are associated with spontaneous recovery, whereas chronic infection is associated with a less vigorous immune response in the peripheral blood and liver (2,6,9,11,19,22,31). The only animal model of HCV infection, the chimpanzee, has provided additional valuable insights into the importance of both CD4 ϩ and CD8 ϩ responses in controlling infection (4,8,30). However, the small numbers of individuals who can be identified as having spontaneous recovery and the retrospective nature of such studies may underestimate the true rates of clearance.The major risk factor for transmission of HCV is percutaneous or parenteral exposure to infected blood or blood products. However, sexual transmission may play a role in some cases, although the exact extent to which this is true and the precise determinants of transmission are as yet unknown. In this study we took a...

In conclusion, autologous stem cell therapy can improve the surgical outcome in cirrhotic livers and should be considered as an adjuvant treatment in such patients undergoing hepatic resection.