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

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