title: Analysis of safety and efficacy of pegylated-interferon alpha-2a in hepatitis C virus positive hemodialysis patients: results from a large, multicenter audit.
abstract: BACKGROUND
  Hepatitis C virus (HCV) infection rates are still high in hemodialysis (HD) centers in developing countries. Standard interferon (IFN) monotherapy is associated with good results in HCV-positive patients (more than 30% rate of sustained virological response) but with poor tolerance. Pegylated interferon (PEG-IFN) is better tolerated and has a more sustained antiviral effect in the general population. There have been no large trials to date with PEG-IFN in hemodialysis populations.
  
  
  METHODS
  We report the largest series to date of HCV+ HD patients (n=78) treated with PEG-IFN alfa -2a 135 microg s.c. weekly monotherapy. The primary outcomes were (a) efficacy - assessed by the viral response at 12, 48 weeks and 6 months after completion of therapy, and (b) rate of serious adverse events.
  
  
  RESULTS
  In 48/78 (61.5%) patients an early (12 weeks) viral response was obtained. Viral end-of-treatment response (ETR) was evaluated in the 21 patients (26.9%) who reached week 48 on therapy: only 15 subjects (19.2% of the initial population) had undetectable HCV-RNA levels. In these 15 patients, a sustained viral response (SVR) was recorded in 11 - i.e. 14.1% of the initial intention-to-treat (ITT) population. A high prevalence of noncompliance (32%) and of adverse events (83%) was recorded; minor adverse effects (flu-like syndrome, mild-to-moderate thrombocytopenia, leukopenia and anemia) responded to symptomatic therapy or dose reduction, but often caused lack of compliance. The incidence rate of serious adverse events was 0.19/patient-year (median time to event 20.5 weeks), and incidence of deaths was 0.11/patient-year.
  
  
  CONCLUSIONS
  In dialysis patients, PEG-IFN alfa -2a is poorly tolerated and associated with a high number of serious adverse events, causing a significant lack of compliance/discontinuation of therapy. In this largest HCV-positive hemodialysis population survey, we report a low sustained viral response in an ITT analysis, compared with previously published historical data using non-PEG-IFN, a low compliance rate and an unsatisfactory overall safety profile, not supporting the superiority of PEG-IFN monotherapy.
authors.affiliation: Dialysis Center, 'Dr. C.I. Parhon' University Hospital, Iasi and The Romanian Renal Registry, Bucharest, Romania. acovic@xnet.ro
authors.forename: Adrian
authors.initials: A
authors.lastname: Covic
authors.forename: Irinel-Doina
authors.initials: ID
authors.lastname: Maftei
authors.forename: Nicoleta G I
authors.initials: NG
authors.lastname: Mardare
authors.forename: Florentina
authors.initials: F
authors.lastname: Ioniţă-Radu
authors.forename: Camelia
authors.initials: C
authors.lastname: Totolici
authors.forename: Liliana
authors.initials: L
authors.lastname: Tuţă
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Golea
authors.forename: Maria
authors.initials: M
authors.lastname: Covic
authors.forename: Carmen
authors.initials: C
authors.lastname: Volovăţ
authors.forename: Paul
authors.initials: P
authors.lastname: Gusbeth-Tatomir
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mircescu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D011994:Recombinant Proteins; D006435:Renal Dialysis; D012383:Romania
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a