The viral genotype may influence the response to interferon sion and more efficient antiviral immune response, is still (IFN) treatment in chronic hepatitis C virus (HCV) infection. unclear. To characterize potential mechanisms responsible for this ef-Several factors including viral load, disease severity, age fect, we assessed whether IFN modulation of HCV-specific and duration of infection, and genotype of the infecting virus T-cell responses differs in patients infected by different genohave been shown in different studies to have a predictive types. The T-cell response to HCV core protein was sequenvalue for the outcome of the IFN treatment. 2 Although definitially analyzed before and during IFN treatment in two groups tive studies are still needed to define the influence of genoof patients chronically infected with HCV genotype 1b (eight type, a higher rate of long-term response to IFN has been patients) or 2c (eight patients). Overlapping 20 mer peptides reported in genotypes 2 and 3 compared with genotype 1bcorresponding to the amino acid sequence of the prevalent infected patients. 2 viral population identified in the serum of each patient were To characterize the mechanisms by which different genoused for the analysis of the T-cell proliferative response to types might influence responsiveness to IFN, we studied the avoid possible problems caused by amino acid differences effect of IFN treatment on the antiviral T-cell response in between infecting virus and HCV proteins used in vitro. Reeight patients with chronic hepatitis C infected by genotype combinant HCV core antigen was used in parallel. The level 1b and eight infected by genotype 2c. The study was focused of viremia was monitored by competitive polymerase chain on the T-cell response to hepatitis C virus (HCV) core antireaction (PCR). The T-cell response to HCV peptides and gen because of its high immunogenicity at the T-cell level. recombinant core protein detected throughout the follow-up To limit possible problems arising from the use of proteins was significantly more vigorous in genotype 2c-than in genowith amino acid sequences different from those of the intype 1b-infected patients. This difference was the result of fecting virus for T-cell analysis in vitro, the core region of a greater enhancement of the T-cell response caused by IFN the prevalent viral strains infecting each patient was setreatment in genotype 2c-compared with genotype 1b-inquenced, and different panels of synthetic peptides correfected patients. The different IFN modulatory effect on T sponding to the different sequences were used to stimulate cells from genotype 1b-and genotype 2c-infected patients individual T-cell responses. illustrates an aspect of the virus-host interaction, which may Results show a different behavior of the HCV core-specific contribute toward the explanation of why different genotypes T-cell response in the two groups of patients; the response differ in responsiveness to IFN treatment. (HEPATOLOGY was significantly enhanced by IFN treatment in patients in-1997;26:792-797.)
fected with genotype 2c, whereas a weaker effect was ob-Interferon (IFN) treatment has a beneficial and long-lastserved in patients infected with genotype 1b. ing effect in approximately 20% of patients with chronic PATIENTS AND METHODS hepatitis C. 1 Whether this effect is directly antiviral or is caused by the IFN immunoregulatory activity, leading to Patients. Sixteen patients with chronic hepatitis C (12 males and 4 females; mean age, 49 years) of sporadic origin were selected for this study on the basis of the HCV genotype; 8 were infected by Abbreviations: IFN, interferon; HCV, hepatitis C virus; PCR, polymerase chain genotype 1b, and 8 by genotype 2c. reaction; PBMC, peripheral blood mononuclear cells.