EFFECTS OF CIRRHOSIS, INTERFERON AND AZATHIOPRINE ON ADVERSE EVENTS IN PATIENTS WITH CHRONIC HEPATITIS-C TREATED WITH RIBAVIRIN

To determine adverse events of ribavirin in the treatment of chronic h epatitis C, 41 patients (18 with cirrhosis), treated with ribavirin at an initial dose of 600-1200 mg day(-1), were analysed retrospectively (six patients were treated twice because adverse effects during the f irst treatment necessitated cessation of ribavirin), Indications for r ibavirin included a contraindication (n = 15) an intolerance (n = 11) or a nonresponse (n = 15) to interferon (IFN), Ribavirin was combined with IFN 3 million units (MU) three times weekly for 15 patients and w ith azathioprine for six patients (five of whom were transplant patien ts), No cirrhotics and only one patient treated with ribavirin + IFN r eceived azathioprine. The mean duration of treatment was 5 months (ran ge 1-18 months). Sixteen of 47 treatments (34%) with ribavirin were st opped: four because of vomiting (8.5%), two for psychiatric disorder, one for dry cough, one for an unrelated cause, and eight (at 1-2 month s) because of a fall in the level of haemoglobin (Hb) of 4.6 g dl(-1) (range 2.7-5.9 g dl(-1)); however, according to the rules of internati onal protocol, we would have expected only four treatments (two in pat ients receiving azathioprine) with Hb < 8.5 g dl(-1) to be stopped, Th e decrease in Hb level occurred more slowly in patients treated with I FN plus ribavirin than in patients treated with ribavirin alone and wa s of lower clinical significance in patients with cirrhosis than in pa tients without cirrhosis. After exclusion of patients receiving azathi oprine, there was no significant difference in the fall of Hb level be tween cirrhotic and non-cirrhotic patients and between patients treate d with IFN plus ribavirin and patients treated with ribavirin alone. I nterestingly, the platelet count of patients treated with IFN plus rib avirin fell less than in patients treated with IFN alone, The most imp ortant and expected adverse event associated with ribavirin was haemol ysis, Anaemia < 8.5 g dl(-1), requiring cessation of ribavirin therapy , was present in 9% of patients and was worsened by azathioprine. Abdo minal discomfort and dry cough were other, potentially important, clin ical adverse events found in our study.