A survey of adverse events in 11 241 patients with chronic viral hepatitis treated with alfa interferon

Abstract

AIMS The aim of this study was to assess the incidence of fatal, life-threatening side effects and the de novo appearance of non-hepatic morbidity during interferon alfa therapy for chronic viral hepatitis. The relationship of these adverse events to actual total dose and duration of interferon was also evaluated. METHODS We conducted a retrospective study at 73 Italian centers of 11,241 consecutive patients with chronic viral hepatitis who underwent interferon alfa treatment. RESULTS Five patients died during interferon therapy due to liver failure (n = 4) or complications arising from sepsis. Life-threatening side effects were observed in eight patients: two cases where depression developed and led to a suicide attempt and six patients with bone marrow suppression (granulocytes < 500/mm3 or platelets < 25,000/mm3). These symptoms and signs completely disappeared after interferon withdrawal. During interferon treatment, 131 patients developed the following de novo non-hepatic disorders: symptomatic thyroid disease (n = 71), impotence (n = 5), systemic autoimmune disease (n = 5), immune-mediated dermatologic disease (n = 14), diabetes mellitus (n = 10), cardiovascular disease (n = 7), psychosis n = 10), seizures (n = 4), peripheral neuropathy (n = 3) and hemolytic anemia (n = 2). Most of these complications are reversible or can be ameliorated. Fatal or life-threatening side effects were not related to actual total dose or duration of interferon alfa, while the majority of patients with de novo non-hepatic morbidity received medium/high doses (> 200 million units) of interferon alfa or were treated for periods longer than 16 weeks (68% and 80%, respectively). CONCLUSIONS Treatment with interferon alfa may have fatal or life-threatening side effects, their incidence in this study being low (0.04% and 0.07%, respectively) and perhaps no different than in untreated patients with chronic viral hepatitis. Moreover de novo non-hepatic morbidity occurred in 1.2% of patients, and the dose and duration of interferon therapy seem important in determining the frequency of this complication. The development of clinically-overt thyroid disease was most common.