Improvement of the course of hepatitis C following cytosine arabinoside as conditioning treatment prior to bone marrow transplantation

To investigate the effect of high doses of cytosine arabinoside (AraC) on liver function in non-A, non-B hepatitis, we prospectively followed 11 leukemic patients with posttransfusion hepatitis at the time of conditioning before bone marrow transplantation. Diagnosis of non-A, non-B hepatitis was based on a sustained elevation of serum alanine aminotransferase (ALT) (greater than or equal to 2.5 times the upper limit of normal), negative serology for hepatitis A and B viruses, cytomegalovirus and Epstein-Barr virus and, in eight out of nine surviving patients, on antihepatitis C sero-conversion. Conditioning included high dose AraC (3 g/m(2)/12 h) on day -6 and day -5, cyclophosphamide (60 mg/kg) on day -4 and day -3 and total body irradiation (day -1, 800 cGy). Ten out of 11 patients exhibited a striking reduction in ALT level already apparent within 24 h following AraC administration and sustained until day + 29. Mean (+/- SD) ALT level on day -6 was 242( +/- 138)IU/l; on day -3, 161 ( +/- 100) IU/l (P < 0.001); and on day + 4, 60( +/- 27) IU/l. After day + 29, a progressive rise in ALT concentrations was again observed in all patients. High doses of AraC might thus exert a potent inhibitory effect on HCV replication in vivo which warrants further investigation.