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 hepatitis C, 41 patients (18 with cirrhosis), treated with ribavirin at an initial dose of 600-1200mg day(-1), were analysed retrospectively (six patients were treated twice because adverse effects during the first treatment necessitated cessation of ribavirin). Indications for ribavirin included a contraindication (n = 15) an intolerance (n = 11) or a non-response (n = 15) to interferon (IFN). Ribavirin was combined with IFN 3 million units (MU) three times weekly for 15 patients and with azathioprine for six patients (five of whom were transplant patients). No cirrhotics and only one patient treated with ribavirin + IFN received azathioprine. The mean duration of treatment was 5 months (range 1-18 months). Sixteen of 47 treatments (34%) with ribavirin were stopped: four because of vomiting (8.5%), two for psychiatric disorder, one for dry cough, one for an unrelated cause, and eight (at 1-2 months) 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 international protocol, we would have expected only four treatments (two in patients receiving azathioprine) with Hb < 8.5 g dl(-1) to be stopped. The decrease in Hb level occurred more slowly in patients treated with IFN plus ribavirin than in patients treated with ribavirin alone and was of lower clinical significance in patients with cirrhosis than in patients without cirrhosis. After exclusion of patients receiving azathioprine, there was no significant difference in the fall of Hb level between cirrhotic and non-cirrhotic patients and between patients treated with IFN plus ribavirin and patients treated with ribavirin alone. Interestingly, the platelet count of patients treated with IFN plus ribavirin fell less than in patients treated with IFN alone. The most important and expected adverse event associated with ribavirin was haemolysis. Anaemia < 8.5 g dl(-1), requiring cessation of ribavirin therapy, was present in 9% of patients and was worsened by azathioprine. Abdominal discomfort and dry cough were other, potentially important, clinical adverse events found in our study.