NORMALIZATION OF DEPRESSED NATURAL-KILLER ACTIVITY AFTER INTERFERON-ALPHA THERAPY IS ASSOCIATED WITH A LOW-FREQUENCY OF RELAPSE IN PATIENTSWITH CHRONIC HEPATITIS-C

In the present study, we found that human recombinant interferon-alpha (rIFN-alpha) given at a dose of 3 x 10(6) units thrice weekly for thre e months, and 1,5 x 106 units thrice weekly for the next three months, was able to restore depressed natural-killer (NK) activity to normal values in 12 out of 21 chronic hepatitis C patients positive for anti- HCV antibodies. In all of these patients, NK normalization was still s ustained after three months from suspension of therapy. Eighteen patie nts also showed a normalization of the alanine aminotransferase (ALT) level by the end of treatment (responder patients), independently of c hanges in NK activity. No significant improvement in either NK activit y or aminotransferase levels was seen among 20 untreated patients. In 8 responder patients (1 with normalized and 7 with low NK activity), A LT levels returned to pre-therapy values within three months after sus pension of r/FN-alpha administration (relapse). We found that patients who normalized NK activity had a lower frequency of relapse as compar ed to patients with low NK activity by the end of treatment (p > 0.01) . Immunofluorescence analysis of biopsy-derived liver tissue revealed that r/FN-alpha was able to induce strong MHC class I antigen expressi on on hepatocytes of treated patients, but this was not related to the clinical course.