Response in Patients with Chronic HCV Hepatitis to Treatment with Interferon-alpha

Twelve patients with chronic hepatitis C received interferon-alpha at doses of 3 million units (11 patients) or 6 millions units (1 patient) 3 times per week for 52 weeks. The patients were evaluated for clinical response, and total blood cell count, B and T lymphocyte count, subtyping of CD4+ and CDS+ lymphocytes, blastic transformation of lymphocytes after stimulation with phytohemagglutinin and concanavalin-A, and liver function tests. Liver biopsies with immunohistochemical methods were done before and after treatment in 7 patients. Blood tests were done every 4 weeks in all 12 patients. Serum beta-2-microglobulin was measured before treatment and after 32 and 52 weeks. Patients with liver disease due to other causes (autoimmune disease and HIV infection) were excluded. The following results were obtained: 1) Four patients improved with treatment (4/12 = 33%) during the 52 week treatment period; 3 of them responding completely and one partially. Two others who were not considered responders maintained ALT levels below 1.5x the normal range after the end of therapy. One of these had received the higher dose of interferon-alpha. Histopathologically, 10 patients improved (10/12 = 83%), one presented progression of the disease and one did not show significant changes with treatment; 2) Immunological evaluation before and after treatment did not show significant differences except for total blood lymphocyte count, which was decreased after treatment; 3) T and CD4+ lymphocyte counts in liver tissue were significantly decreased after treatment, but there was no change in the pattern of their distribution within the hepatic parenchyma. These findings confirm that interferon-alpha is effective in patients with hepatitis C, and suggest that the drug has a predominantly antiviral effect in chronic hepatitis caused by C virus, and that the hepatocellular damage observed in these cases is mainly due to the cytopathic effect of the virus rather than immunopathologic processes.