title: Risk of infections during interferon-based treatment in patients with chronic hepatitis C virus infection and advanced hepatic fibrosis.
abstract: OBJECTIVE
  Pegylated interferon-based treatment is still the backbone of current hepatitis C therapy and is associated with bone marrow suppression and an increased risk of infections. The aim of this retrospective cohort study was to assess the risk of infections during interferon-based treatment among patients with chronic hepatitis C virus (HCV) infection and advanced hepatic fibrosis and its relation to treatment-induced neutropenia.
  
  
  METHODS
  This cohort study included all consecutive patients with chronic HCV infection and biopsy-proven bridging fibrosis or cirrhosis (Ishak 4-6) who started treatment between 1990 and 2003 in five large hepatology units in Europe and Canada. Neutrophil counts between 500-749/μL and below 500/μL were considered as moderate and severe neutropenia, respectively.
  
  
  RESULTS
  This study included 723 interferon-based treatments, administered to 490 patients. In total, 113 infections were reported during 88 (12%) treatments, of which 24 (21%) were considered severe. Only one patient was found to have moderate neutropenia and three patients were found to have severe neutropenia at the visit before the infection. Three hundred and twelve (99.7%) visits with moderate neutropenia and 44 (93.6%) visits with severe neutropenia were not followed by an infection. Multivariable analysis showed that cirrhosis (odds ratio [OR] 2.85, 95% confidence interval [CI] 1.38-5.90, P=0.005) and severe neutropenia at the previous visit (OR 5.42, 95% CI 1.34-22.0, P=0.018) were associated with the occurrence of infection, while moderate neutropenia was not. Among a subgroup of patients treated with pegylated interferon, severe neutropenia was not significantly associated (OR 1.63, 95% CI 0.19-14.2, P=0.660).
  
  
  CONCLUSIONS
  In this large cohort of patients with bridging fibrosis and cirrhosis, infections during interferon-based therapy were generally mild. Severe interferon-induced neutropenia rarely occurred, but was associated with on-treatment infection. Moderate neutropenia was not associated with infection, suggesting that current dose reduction guidelines might be too strict.
authors: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Raoel
authors: R
authors: Maan
authors: Adriaan J
authors: AJ
authors: van der Meer
authors: Bettina E
authors: BE
authors: Hansen
authors: Jordan J
authors: JJ
authors: Feld
authors: Heiner
authors: H
authors: Wedemeyer
authors: Jean-François
authors: JF
authors: Dufour
authors: Frank
authors: F
authors: Lammert
authors: Michael P
authors: MP
authors: Manns
authors: Stefan
authors: S
authors: Zeuzem
authors: Harry L A
authors: HL
authors: Janssen
authors: Robert J
authors: RJ
authors: de Knegt
authors: Bart J
authors: BJ
authors: Veldt
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007239:Infections / Q000453:epidemiology / Q000209:etiology*; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects*; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects*; D017410:Practice Guidelines as Topic / Q000592:standards; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012306:Risk; D012720:Severity of Illness Index
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a
keywords: antiviral treatment; chronic hepatitis C; cirrhosis; infections; neutropenia; side effects