CYCLOSPORINE THERAPY AFFECTS AMINOTRANSFERASE ACTIVITY BUT NOT HEPATITIS-C VIRUS-RNA LEVELS IN CHRONIC HEPATITIS-C

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, bur: it is not universally effective and is often limited by side eff ects. Cyclosporine A (CsA) is a potent immunosuppressant widely used i n organ transplantation. We conducted a pilot study to determine wheth er CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male:female 9:1 ) who did not respond to IFN therapy previously and who had elevated s erum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their m ean duration of hepatitis was 15 years. Oral CsA was given for 3 month s in a dose that was increased at 1 month intervals from 1.5-2.0 to 2. 0-3.0 and 3.0-4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild nonsymptomatic hyperten sion. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 +/ - 82 to 62 +/- 48 IU/L; P < 0.02). The ALT levels fell to the normal r ange in five patients, although once therapy was discontinued the enzy me levels tended to return to pretreatment levels. Serum aspartate ami notransferase and g-glutamyl transpeptidase levels similarly decreased . The serum HCV-RNA titre, determined by competitive RT-PCR, did nor c hange in any patient throughout the study period. There were no apprec iable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkalin e phosphatase levels. These findings suggest: that CsA, even in a rela tively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic hepatitis C, although an antivi ral effect was not noted.