The mortality, only observed in patients treated with peginterferon and ribavirin combination therapy, raises the issue of whether the peg molecule increases the severity of pneumonitis once it arises. Interferon toxicity is generally dose and duration dependent [26] , which leads us to speculate that pulmonary toxicity may occur more severely with long-acting peginterferon; however, we saw no effect of dosage on the occurrence of pneumonitis. Patients died due to different causes (e.g., hypoxia-induced cerebral edema, acute cholestatic hepatitis, and multi-organ failure), all were induced by complications after initially interstitial pneumonitis. One alternative explanation for the increased mortality might be that all patients with peginterferon were also treated with ribavirin, although ribavirin per se is not associated with pulmonary toxicity.