High Risk of Infection During Triple Therapy with First-Generation Protease Inhibitors: A Nationwide Cohort Study.
OBJECTIVE
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 with correction 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 (34 severe). 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).


CONCLUSIONS
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.
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Floor A C
FA
Berden
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Inke M J M
IM
van Zwietering
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Raoel
R
Maan
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Robert J
RJ
de Knegt
Department of Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
Wietske
W
Kievit
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands. joostphdrenth@cs.com.
Joost P H
JP
Drenth
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage; D000998:Antiviral Agents / Q000009:adverse effects*; D016009:Chi-Square Distribution; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006760:Hospitalization; D006801:Humans; D016867:Immunocompromised Host; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands / Q000453:epidemiology; D009503:Neutropenia / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology; D016017:Odds Ratio; D009894:Opportunistic Infections / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology; D011480:Protease Inhibitors / Q000009:adverse effects*; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D016896:Treatment Outcome; D055815:Young Adult
D000890:Anti-Infective Agents; D000998:Antiviral Agents; D011480:Protease Inhibitors