title: Gamma-glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon-alpha-2b in chronic hepatitis C non-responders.
abstract: BACKGROUND
  High-dose peginterferon-alpha (PegIFN-alpha) induction and prolongation of therapy may be an option to improve sustained virological response (SVR) rates among hepatitis C virus (HCV) non-responders, although a higher and a longer dosing of PegIFN-alpha may intensify side effects.
  
  
  METHODS
  We randomized 53 patients, who previously failed with standard IFN-alpha+/-ribavirin, to a high-dose induction and an extended regimen with PegIFN-alpha-2b [3.0 microg/kg once weekly (q.w.) 12 weeks-->2.0 microg/kg q.w. 12 weeks-->1.5 microg/kg q.w. 48 weeks] or a standard regimen (1.5 microg/kg q.w. 48 weeks). All patients received daily weight-based ribavirin (800-1200 mg/day). The short-form 36 health survey was used to evaluate health-related quality of life (HRQL).
  
  
  RESULTS
  Intention-to-treat analysis showed no significant difference in SVR rate (44% vs. 37%, P=0.62) and relapse rate (9% vs. 31%, P=0.17) between experimental and standard treatment. Overall, 80% of the [positive predictive value (PPV)] patients with rapid virological response (RVR, HCV-RNA negativity at week 4) achieved SVR. No significant dose-related differences in HRQL were seen between both groups. At baseline, genotype 2 or 3 [odds ratio (OR): 7.4, 95% confidence interval (CI): 1.4-33.3, P=0.01] and gamma-glutamyltransferase (GGT) levels <2 x ULN (upper limit of normal) (OR: 6.76, 95% CI: 1.5-31.3, P=0.009) were significantly associated with SVR. Multivariate logistic regression at week 4 showed that only baseline GGT <2 x ULN (OR: 7.3, 95% CI: 1.4-38.5, P=0.01) and RVR (OR: 15.6, 95% CI: 3.2-76.9, P<0.001) were independently predictive for SVR.
  
  
  CONCLUSIONS
  Retreatment with PegIFN-alpha-2b and ribavirin for a minimum of 48 weeks should be considered in all patients unresponsive to previous IFN-based therapies. Baseline GGT values and RVR are highly predictive for retreatment outcome.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jilling F
authors.initials: JF
authors.lastname: Bergmann
authors.forename: Jan M
authors.initials: JM
authors.lastname: Vrolijk
authors.forename: Peter
authors.initials: P
authors.lastname: van der Schaar
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vroom
authors.forename: Bart
authors.initials: B
authors.lastname: van Hoek
authors.forename: Annet
authors.initials: A
authors.lastname: van der Sluys Veer
authors.forename: Richard A
authors.initials: RA
authors.lastname: de Vries
authors.forename: Elke
authors.initials: E
authors.lastname: Verhey
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Brouwer
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Solko W
authors.initials: SW
authors.lastname: Schalm
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011446:Prospective Studies; D011788:Quality of Life; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D005723:gamma-Glutamyltransferase; C417083:peginterferon alfa-2b