Pretreatment symptoms and dosing regimen predict side-effects of interferon therapy for hepatitis C

We analysed data from a multicentre interferon (IFN) treatment trial to eva luate symptoms in patients with chronic hepatitis C and to identify factors that might predict development of debilitating IFN side-effects. Two hundr ed and twenty-two patients (120 US, 102 French) received 3 or 5 million uni ts (MU) of IFN-alpha three times weekly (t.i.w.) for 3 months. Those who ha d detectable hepatitis C virus (HCV) RNA, as detected by the branched DNA s ignal amplification (bDNA) assay, at 3 months were intensified to daily the rapy, while patients who were bDNA negative continued t.i.w. dosing for the subsequent 3 months of treatment. Symptoms were assessed at baseline, and adverse effects were evaluated at 6 months of therapy. Prior to treatment, the most common symptom that interfered with daily functioning was fatigue, occurring in 25% of patients. The frequency of debilitating fatigue, myalg ia, arthralgia, headache, the presence of dry eyes and dry mouth, and use o f antidepressant medication increased significantly from baseline to 6 mont hs of IFN therapy (all P < 0.01). In multivariate analysis, the development of a debilitating side-effect at 6 months of treatment was associated with the presence of that symptom prior to therapy in all cases. Symptoms and a dverse effects varied by gender and country. Compared with patients maintai ned on t.i.w. dosing, those who were dose intensified to daily IFN reported more debilitating fatigue, malaise, myalgia, arthralgia, fever, nausea, an d headache, and the presence of dry mouth (all P < 0.05). In conclusion, pa tient characteristics, including pretreatment symptoms, gender and national ity, as well as daily IFN dosing are associated with the development of deb ilitating adverse effects on IFN therapy.