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.