Immunological and virological predictors of outcome during interferon-alpha therapy of chronic hepatitis C

Results from a multicentre, clinical trial of interferon-alpha 2a (IFN-alph a 2a) for the treatment of chronic hepatitis C are reported. Serum hepatiti s C virus (HCV) RNA levels were monitored as follows: before, and 2 days af ter, the first administration of IFN-alpha 2a; during and at the end of tre atment; and 6 months after completion of therapy. Peripheral blood lymphocy te subpopulations were measured, by two-colour flow cytometry, before and 3 h after the first intramuscular (i.m.) administration of 9 mega units (MU) of IFN-alpha 2a. Virological responders had a significantly lower pretreat ment level of CD11(+) CD8(-) lymphocytes. Biochemical responders had signif icantly lower pretreatment levels of CD11(-) CD8(+), human leucocyte antige n (HLA) DR- CD4(-) and HLA DR- CD8(+) populations, and a higher pretreatmen t HLA DR+ CD4(-) population. These pretreatment differences disappeared 3 h after the first i.m. administration of IFN-alpha 2a. CD11(-) CD8(+) and HL A DR+ CD8(+) cell populations became significantly lower in virological res ponders 3 h after the first i.m. administration of IFN-alpha 2a. HLA DR+ CD 4(+) cell populations were increased less in biochemical responders. Thus, T-lymphocyte subpopulations were different between responders and non-respo nders to IFN therapy and IFN-modulated host immunity. Multivariate analysis showed that the pretreatment CD11(+) CD8(-) cell population was an indepen dent predictive factor of response to therapy. On the other hand, patients whose serum HCV RNA cleared or decreased within the first 2 days of IFN-alp ha 2a therapy were more likely to achieve a virological response. This pred ictive factor, however, was not an independent factor by multivariate analy sis. These results suggest that host immunity is an important factor in res ponse to IFN therapy, and HCV clearance within the first 2 days is a good p redictive factor of response.