High Risk of Infection During Triple Therapy with First- Generation Protease Inhibitors: A Nationwide Cohort Study
Floor A.C. Berden1, Inke M.J.M. van Zwietering1, Raoel Maan2, Robert J. de Knegt2, Wietske Kievit3, Joost P.H. Drenth1
1) Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen,
2) Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam,
3) Department of Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands
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.
Key words: antiviral agents – boceprevir – telaprevir – hepatitis C infection – neutropenia – risk factors.
Abbreviations: ANC: absolute neutrophil count; CHC: chronic hepatitis C; COPD: chronic obstructive
pulmonary disease; DAAs: direct acting antivirals; DM: diabetes mellitus; HCV: hepatitis C virus; PegIFN:
pegylated interferon alpha; PI: protease inhibitor; UTI: urinary tract infection.