Ratio of serum gamma-GT/ALT rather than ISDR variability is predictive forinitial virological response to IFN-alpha in chronic HCV infection

Chronic hepatitis C virus (HCV) infection in humans is treated at present w ith interferon (IFN)cu. Because the proportion of patients responding to th erapy with sustained or even just with transient elimination of viral RNA i s low, several potential prognostic parameters have been evaluated to predi ct the outcome of the therapy. The present study aimed to prove the validit y of a predictive parameter described previously for initial virological re sponse, namely the ratio of serum gamma-glutamyltransferase/aranine transam inase (gamma-GT/ALT) activity in connection with virus genotypes la, Ib, an d 3a, prospectively and to compare the predictive value of these combined p arameters with amino acid variability within the interferon sensitivity det ermining region (ISDR). The prospective analysis confirmed previous data on the predictive value of the serum gamma-GT/ALT ratio. Concerning ISDR vari ability, the majority of ISDR sequences obtained from the mostly nonrespond ing type Ib-infected individuals (23/28) resembled nonmutant types (27/28). Isolates from type 3a-infected patients responding to therapy in the major ity of cases (13/20) exclusively resembled nonmutant types when compared wi th databank type 3a sequences, but were mutant when compared with the proto type sequence HCV-J. However, the initial virological responsiveness among both type 1b- and type Ba-infected patients did not correlate to ISDR varia bility. In contrast, virological responsiveness was closely related to seru m gamma-GT/ALT ratio. The data are not necessarily contrary to the concept that the number of amino acid exchanges within the ISDR compared with the p rototype HCV-J sequence is related to some extent to IFN-a sensitivity. The ratio of serum gamma-GT/ALT in combination with HCV genotype, however, was found to be a more reliable and stringent predictive parameter. (C) 1999 W iley-Liss, Inc.