Expectoration of Large Bronchial Casts Secondary to the Treatment of Chronic Hepatitis C With Pegylated Interferon and Ribavirin

Infections caused by the hepatitis C virus (HCV) are currently a serious public health problem. It is estimated that 3 to 4 million new cases occur worldwide every year. Of the individuals with acute HCV infections, 55% to 85% will be chronically infected and will thus be at risk of liver damage, cirrhosis and hepatocellular carcinoma.1,2 In total, more than 170 million people (i.e., ≈2% of the world’s population) are infected with HCV. The best treatment currently available is a combination of pegylated interferon and ribavirin.2–6 Interferons are potent cytokines with antiviral, antiproliferative and immunomodulatory activities.7 Interferons are linked to cell surface receptors and cause a cascade of intracellular events, including the induction of the transcription of genes that inhibit cell growth and of genes that alter cell differentiation, oncogene expression and the expression of antigens on the cell surface. In turn, these effects increase macrophage phagocytosis and the cytotoxicity of lymphocytes in relation to target cells and hinder mechanisms of viral replication in parasitic cells. The treatment of hepatitis C has various limitations: cost, efficacy and, principally, adverse effects. The numerous side effects observed range from the trivial, such as influenza-like symptoms, anorexia, fatigue, headache, nausea myalgia, diarrhea, local reactions to the application of the medication, alopecia and pruriginous rash, to the severe, such as psychiatric symptoms, cytopenias and respiratory symptoms (cough and dyspnea). Among the rarest and most potentially deleterious adverse manifestations are pancreatitis, profound medullary depression and cardiotoxicity, which can lead to cardiac failure and sudden death.2,3,8,9 Finally, it has been suggested that interferon alpha therapy is associated with the development and exacerbation of autoimmune diseases.3 Severe lung toxicity is associated with interferon alpha monotherapy as well as combination therapies involving ribavirin and conventional or pegylated interferon alpha. There have also been reported cases of interstitial pneumonia,2,10 bronchiolitis obliterans organizing pneumonia (BOOP), sarcoidosis and severe profiles of asthma exacerbation.9 For example, Kuno et al. described three cases involving patients with chronic hepatitis C who developed interstitial pneumonitis during treatment with interferon alpha and presented complete resolution of the symptoms after discontinuation of the medication.11 Nevertheless, pulmonary complications associated with interferon alpha therapy are rare. In the literature, the pathology most commonly associated with interferon alpha therapy is interstitial pneumonitis, followed by sarcoidosis-like conditions leading to the formation of noncaseating granulomas.3,7,8 Ribavirin is a purinic nucleoside analog with a modified base and a D-ribose sugar. Although the mechanisms of ribavirin action continue to be the object of speculation, it is possible that ribavirin acts as an immunostimulating antiviral agent and has recently been proposed to be a stimulator of inducible interferon genes.12 When combined with interferon alpha, ribavirin contributes greatly to obtaining a sustained virological response (SVR) and to reducing recurrence. Ribavirin side effects are hemolytic anemia, fatigue, rash and cough. However, there have been no reports of severe cases or cases with pronounced symptoms.