Background & Aims: Peginterferon (PegIFN) remains the backbone of therapy for chronic hepatitis C (CHC) in economically constrained regions. However, PegIFN may cause neutropenia and addition of a protease inhibitor can increase the likelihood of neutropenia. The aims of this study were to assess the occurrence of clinically relevant infections during first-generation protease inhibitor based therapy and its risk factors as well as the relation to treatment-induced neutropenia. Methods: This multicenter (n=45) retrospective cohort study included CHC patients treated in the Netherlands. Based on absolute neutrophil count, categories of neutropenia were defined as: severe (<500/μL), moderate (500-750/μL) and mild (750-1500/μL). Likewise, infections were classified as severe (intravenous antibiotics/ hospitalization) and moderate (anti-infective treatment). We assessed risk factors for infections using multivariable regression analysis adjusting for multiple measurements. Results: We included 467 CHC patients, 319 (68%) were male and 111 (24%) had cirrhosis. A total of 185 clinically relevant infections (34 severe) occurred in 145 patients (31%). During treatment 310 patients experienced neutropenia (severe, n=34). Multivariable analysis identified female sex (OR 1.7, 95%CI 1.2- 2.5), chronic obstructive pulmonary disease (COPD) (OR 2.7, 95%CI 1.6- 4.5) and diabetes mellitus (OR 1.7, 95%CI 1.0-3.0) as risk factors for infections. Neutropenia at the previous visit was not associated with infection (univariable analysis: OR 0.9, 95%CI 0.6-1.3). Conclusion: This study shows that therapy with first generation protease inhibitors was complicated by an infection in 31% of patients. Not neutropenia, but female sex, COPD and diabetes mellitus were independent risk factors for infection. These patients should be monitored carefully once a PegIFN regimen is initiated.

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Journal of Gastrointestinal and Liver Diseases
Department of Gastroenterology & Hepatology

Berden, F. A. C., van Zwietering, I. M. J. M., Maan, R., de Knegt, R., Kievit, W., & Drenth, J. (2016). High risk of infection during triple therapy with first- generation protease inhibitors: A nationwide cohort study. Journal of Gastrointestinal and Liver Diseases, 25(2), 197–204. Retrieved from