SAFETY AND EFFICACY OF INTERFERON ALFA FOR THE TREATMENT OF CHRONIC HEPATITIS C INFECTED SUBJECTS WITH TRANSFUSION DEPENDENT THALASSEMIA IN IRAN

Up to 30% of Iranian adult multi-transfused thalassemic patients are infected with hepatitis C virus (HCV) which can intensify the progression of liver disease caused by iron overload in this group of patients. Our aim was to assess the biochemical and virological response of interferon alfa (INF-α) and its safety in thalassemic patients with chronic HCV infection. This trial was a single center, open label, single treatment prospective study of INF-a (Heberon alfa R, 3 MU, every other day) for a period of 12 months. 29 subjects, 13 to 56 years old (mean ± SD: 25.1 ± 10.4 years), whose serum HCV-RNA was positive and mean ALT remained greater than 1.5 times upper limit of normal in the last 6 months before the study were enrolled. A percutaneous liver biopsy was performed before treatment and all patients underwent monthly assessment for adverse events and monitoring of serum ALT. Qualitative serum HCV-RNA was obtained in months 3 and 6 and at the end of therapy. Pretreatment liver biopsy showed mild fibrosis in 33.3%, moderate fibrosis in 56.7% and cirrhosis in 10% of patients. Siderosis was severe in 14 patients (46.7%). Two nonsplenectomized patients discontinued INF becau'se of mild cytopenia, which resolved in less than one week after interruption of therapy. The following were some of the important adverse events observed during the study period: Flu syndrome in 29(100%), chills or fever>39°C in 14(48%), local pain in 14(48%), transient gastrointestinal symptoms in 13(44%), weakness in 5(17%), local induration in 3(10%) and edema in 2(7%) of the patients. By the end of 12 months of therapy, 15 patients out of 27 (55.6%) had a normal ALT and negative HCV-RNA (complete end-treatment response), they were followed up for a mean duration of 10.5 months (range: 6 to 22 months) and in 8 of them (53.3%) the condition relapsed (abnormal ALT with positive PCR). Viral clearance was a delayed event in our patients (29% by the end of month 3 and 63% by month 7) but ALT normalization occurred in 94% of responders by the end of month 3. Our experience indicates that the cure of HCV -related liver disease in thalassemic patients is not an unrealistic aim and may be achieved with a safe and inexpensive INF preparation (Heberon Alfa R) in a sizeable portion of cases. As opposed to non-thalassemic patients, in whom most viral responses happen in the first 3 months of therapy, in this group of thalassemic patients we found that maximum virologic response happened between 3 to 6 months of therapy. Although INF-a is an effective drug for initial treatment in thalassemic patients infected with HCV, its efficacy with the above dose and duration, for maintaining long term remission is under question.