title: Hepatitis C virus survival curve analysis in naïve patients treated with peginterferon alpha-2b plus ribavirin. A randomized controlled trial for induction with high doses of peginterferon and predictability of sustained viral response from early virologic data.
abstract: OBJECTIVE
  To evaluate the significance of induction with high doses of pegylated interferon -2b (Peg-IFNalpha-2b) and the predictability of sustained virologic response (SVR) in naïve patients with chronic hepatitis C.
  
  
  METHODS
  188 consecutive naïve patients with chronic hepatitis C were enrolled in a randomised controlled clinical trial. Patients were randomised to receive either Peg-IFN -2b 3.0 mcg/kg QW x 12 weeks followed by 1.5 mcg/kg QW x 36 weeks plus 800-1200 mg ribavirin (Arm A) or Peg-IFNalpha-2b 1.5 mcg/kg QW x 48 weeks plus 800-1200 mg ribavirin (Arm B). HCV-RNA was obtained at 0, 4, 8, 12, 16, 24, 48 and 72 weeks. Differences between schemes were evaluated by Kaplan-Meier curves. Predictability of SVR was assessed by two-way contingency table analysis and ROC curve analysis.
  
  
  RESULTS
  From 176 patients, 75 had genotype 1, 15 genotype 2, 75 genotype 3 and 11 genotype 4. No statistical significance emerged in HCV-RNA positivity, side effects and withdrawals between schemes. Patients with genotype 1 achieved lower SVR (46.6%) in comparison to patients with genotypes 2/3 (94.1%, p < 0.001) and 4 (90.9%, p = 0.002). The most appropriate time for estimation of SVR for genotype 1 is week 8 (accuracy = 0.84, AUC = 0.90) while predictability increases with time in genotypes 2/3, reaching maximum accuracy = 0.93 and AUC = 0.76 at week 16.
  
  
  CONCLUSIONS
  Induction with high doses of Peg-IFNalpha-2b does not preclude better outcome and rapid virologic response at 4 weeks of treatment sufficiently predicts SVR. These findings might be useful in an attempt to gain supportive evidence for decision making in difficult-to-treat patients.
authors.affiliation: Department of Medicine, Democritus University of Thrace, 8, Chrisostomou Smirnis Str., GR-68100 Alexandroupolis, Greece. kmimidis@otenet.gr
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mimidis
authors.forename: Vassilios P
authors.initials: VP
authors.lastname: Papadopoulos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Elefsiniotis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Koliouskas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Ketikoglou
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Paraskevas
authors.forename: Spyridon
authors.initials: S
authors.lastname: Kanatakis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Chrysagis
authors.forename: Georgios N
authors.initials: GN
authors.lastname: Dalekos
authors.forename: Christos
authors.initials: C
authors.lastname: Tzathas
authors.forename: Athanasios
authors.initials: A
authors.lastname: Protopapas
authors.forename: Eleni
authors.initials: E
authors.lastname: Gigi
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Tsianos
authors.forename: Georgios
authors.initials: G
authors.lastname: Kartalis
mesh_terms: D000328:Adult; D000998:Antiviral Agents; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008297:Male; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D016019:Survival Analysis
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b