Decline in Pulmonary Function during Chronic Hepatitis C Virus Therapy With Modified Interferon Alfa and Ribavirin

G. R. Foster; S. Zeuzem; S. Pianko; S. K. Sarin; T. Piratvisuth; S. Shah; P. Andreone; A. Sood; W.-L. Chuang; C.-M. Lee; J. George; M. Gould; R. Flisiak; I. M. Jacobson; P. Komolmit; S. Thongsawat; T. Tanwandee; J. Rasenack; R. Sola; I. Messina; Y. Yin; S. Cammarata; G. Feutren; K. Brown


J Viral Hepat. 2013;20(4):e115-e123. 

In This Article

Abstract and Introduction


Rare interstitial lung disease cases have been reported with albinterferon alfa-2b (albIFN) and pegylated interferon alfa-2a (Peg-IFNα-2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg-IFNα-2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety-one patients were randomly assigned 4:4:4:3 to one of four, open-label, 24-week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 μg q4wk or Peg-IFNα-2a 180 μg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X-rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines (≥15%) were observed in 173 patients (48%), and were more frequent with Peg-IFNα-2a and albIFN 1500 μg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg-IFNα-2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFNα/ribavirin therapy and commonly persisted for ≥6 months posttherapy. The underlying mechanism and clinical implications for long-term pulmonary function impairment warrant further research.


Therapy with pegylated interferon-alfa (Peg-IFNα) and ribavirin (RBV) has become the standard of care for the treatment of chronic hepatitis C virus (HCV),[1] but it has been associated with a number of adverse events (AEs), including frequent manifestations of dry cough and dyspnoea.[2] Rare, potentially fatal cases of interstitial pneumonitis have been reported with an incidence ranging between 0.3% and 0.03%.[2,3] Little is known, however, about the chronic effect of IFNα on the lung, and no large-scale prospective study has evaluated the incidence of changes in pulmonary physiology and chest imaging during therapy.

Albinterferon alfa-2b (albIFN) is a fusion polypeptide of recombinant human albumin and recombinant IFNα-2b, with a half-life of ~200 hours and IFNα-like pharmacodynamic properties.[4] Recently, albIFN 900 and 1200 μg injected every 2 weeks in combination with RBV was evaluated in more than 2000 patients and was reported to have similar efficacy to that of Peg-IFNα-2a 180 μg injected once weekly (qwk) for the treatment of chronic HCV.[5,6] Two cases of progressive interstitial lung disease (ILD; one fatal) occurred with albIFN 1200 μg during the course of those trials. Therefore, systematic investigations of pulmonary function and chest imaging were conducted in the present study that evaluated 3 doses of albIFN administered every 4 weeks (q4wk) compared with Peg-IFNα-2a qwk.[7]