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Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data
  1. C Cammà1,
  2. S Bruno2,
  3. F Schepis3,
  4. O Lo Iacono4,
  5. P Andreone5,
  6. A G Gramenzi5,
  7. A Mangia6,
  8. A Andriulli6,
  9. M Puoti7,
  10. A Spadaro8,
  11. M Freni8,
  12. V Di Marco4,
  13. L Cino4,
  14. G Saracco9,
  15. A Chiesa2,
  16. A Crosignani2,
  17. N Caporaso10,
  18. F Morisco10,
  19. M G Rumi11,
  20. A Craxì4
  1. 1Istituto Metodologie Diagnostiche Avanzate, Consiglio Nazionale delle Ricerche, and Cattedra e Unità Operativa di Gastroenterologia, University of Palermo, Palermo, Italy
  2. 2Istituto di Scienze Biomediche, San Paolo University of Milano, Italy
  3. 3Dipartimento di Medicina Sperimentale e Clinica “G Salvatore”, University of Catanzaro, Italy
  4. 4Cattedra e Unità Operativa di Gastroenterologia, University of Palermo, Italy
  5. 5Dipartimento di Medicina Interna, Epatologia, University of Bologna, Italy
  6. 6Divisione di Gastroenterologia, Casa Sollievo della Sofferenza, S Giovanni Rotondo, Italy
  7. 7Clinica Malattie Infettive e Tropicali, University of Brescia, Italy
  8. 8Clinica Medica 1a, University of Messina, Italy
  9. 9Cattedra e Unità Operativa di Gastroenterologia, Ospedale Molinette, University of Torino, Italy
  10. 10Dipartimento di Scienze Alimentari, University Federico II of Napoli, Italy
  11. 11Cattedra e Unità Operativa di Gastroenterologia, IRCCS Ospedale Maggiore, University of Milano, Italy
  1. Correspondence to:
    Dr C Cammà, Via Alcide De Gasperi 50, 90100 Palermo, Italy;


Background and aims: Retreatment with a combination of α interferon (IFN) plus ribavirin of patients with chronic hepatitis C who did not respond to IFN monotherapy has not been assessed in large controlled studies.

Methods: To assess the effectiveness and tolerability of IFN/ribavirin retreatment of non-responders to IFN and to identify predictors of complete (biochemical and virological) sustained response, we performed a meta-analysis of individual data on 581 patients from 10 centres. Retreatment with various IFN schedules (mean total dose 544 mega units) and a fixed ribavirin dose (1000–1200 mg/daily depending on body weight) was given for 24–60 (mean 39.5) weeks.

Results: Biochemical end of treatment and sustained responses were observed in 271/581 (46.6%; 95% confidence interval (CI) 42.6–50.7%) and in 109/581 (18.7%; 95% CI 15.6–22.0%) cases, respectively. Two hundred and six of 532 patients (38.7%; 95% CI 34.6–42.9%) had an end of treatment complete response to retreatment while a complete sustained response occurred in 88 of 559 (15.7%; 95% CI 12.8–18.8%). Fifty four of 581 patients (9.2%; 95% CI 7.0–11.7%) stopped retreatment due to adverse effects. By logistic regression, complete sustained response was predicted independently by age <45 years (p=0.04), by normal pretreatment γ-glutamyltransferase levels (p=0.01), and by a second course total IFN dose of at least 432 mega units (p=0.008).

Conclusions: The overall low probability of effectiveness argues against indiscriminate retreatment of all IFN monotherapy non-responders with IFN/ribavirin. Patients less than 45 years old with normal γ-glutamyltransferase levels who were retreated with high dose long course combination therapy had a complete sustained response rate of 30%.

  • hepatitis C virus
  • interferon
  • meta-analysis
  • randomised controlled trial
  • ribavirin
  • HCV, hepatitis C virus
  • IFN, α interferon
  • MIPD, meta-analysis of individual patient data
  • ETR, end of treatment response
  • SR, sustained response
  • RCT, randomised controlled trial
  • MU, mega units
  • ALT, alanine transaminase
  • ROC, receiver operating characteristic
  • AUC, area under the curve
  • OR, odds ratio
  • NNT, number needed to be retreated

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