Significant pulmonary toxicity associated with interferon and ribavirin therapy for hepatitis C.

OBJECTIVE: The aim of this study was to analyze the clinical presentation and outcomes of significant pulmonary toxicity associated with interferon and ribavirin.
METHODS: We conducted a retrospective review of patients enrolled in four clinical trials at three sites, two academic medical centers and one community practice, and reviewed the literature.
RESULTS: Four patients, while on therapy with interferon a and ribavirin for chronic hepatitis C, developed significant pulmonary signs and symptoms. Further workup, which included lung biopsy in three, revealed bronchiolitis obliterans organizing pneumonia in two, and interstitial pneumonitis in two other cases. There were no other predisposing factors for lung disease identified. Resolution of symptoms occurred in all patients upon discontinuation of interferon and ribavirin, with or without corticosteroid therapy. One of the patients developed pulmonary complications while on a clinical trial of pegylated interferon and represents the first reported case associated with the use of long-acting interferon in chronic hepatitis C infection.
CONCLUSIONS: A spectrum of significant pulmonary toxicity, including bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis, can occur with interferon or pegylated interferon in combination with ribavirin. Though pulmonary toxicity of interferon is well known, these cases represent the first cases reported in the literature with combination therapy. It is likely that pulmonary toxicity may not be investigated in patients on combination therapy because of the frequent pulmonary symptoms with ribavirin. Though usually reversible, at least one case has required long-term steroids with inadequate resolution. Though pulmonary toxicity is rare, symptoms which are more than mild or progressive in nature should likely be investigated.