Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy:: a meta-analysis of individual patient data

被引:22
作者
Cammà, C
Bruno, S
Schepis, F
Lo Iacono, O
Andreone, P
Gramenzi, AG
Mangia, A
Andriulli, A
Puoti, M
Spadaro, A
Freni, M
Di Marco, V
Cino, L
Saracco, G
Chiesa, A
Crosignani
Caporaso, N
Morisco, F
Rumi, MG
Craxì, A
机构
[1] CNR, Ist Metadol Diagnost Avanzate, Palermo, Italy
[2] Univ Palermo, Cattedra Operat Gastroenterol, Palermo, Italy
[3] Univ Palermo, Unita Operat Gastroenterol, Palermo, Italy
[4] San Paolo Univ Milan, Ist Sci Biomed, Milan, Italy
[5] Univ Catanzaro, Dipartimento Med Sperimentale & Clin G Salvatore, Catanzaro, Italy
[6] Univ Bologna, Dipartimento Med Interna, Bologna, Italy
[7] Casa Sollievo Sofferenza, Div Gastroenterol, San Giovanni Rotondo, Italy
[8] Univ Brescia, Clin Malatt Infett & Tropicali, Brescia, Italy
[9] Univ Messina, Messina, Italy
[10] Univ Turin, Osped Molinette, Cattedra Operat Gastroenterol, Turin, Italy
[11] Univ Turin, Osped Molinette, Unita Operat Gastroenterol, Turin, Italy
[12] Univ Naples Federico II, Dipartimento Sci Alimentari, Naples, Italy
[13] Univ Milan, Osped Maggiore, IRCCS, Cattedra Operat Gastroenterol, Milan, Italy
[14] Univ Milan, Osped Maggiore, IRCCS, Unita Operat Gastroenterol, Milan, Italy
关键词
D O I
10.1136/gut.51.6.864
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and aims: Retreatment with a combination of a 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 (Cl) 42.6-50.7%) and in 109/581 (18.7%; 95% Cl 15.6-22.0%) cases, respectively. Two hundred and six of 532 patients (38.7%; 95% Cl 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% Cl 12.8-18.8%). Fifty four of 581. patients (9.2%; 95% Cl 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 gamma-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/ribovirin. Patients less than 45 years old with normal gamma-glutamyltransferase levels who were retreated with high dose long course combination therapy had a complete sustained response rate of 30%.
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页码:864 / 869
页数:6
相关论文
共 32 条
[1]   High dose of interferonα (IFN) plus ribavirin (RIBA) for 6 or 12 months in non responder (NR) patients with chronic hepatitis C (CHC):: Results of a randomized trial [J].
Andreone, P ;
Cursaro, C ;
Gramenzi, A ;
Margotti, M ;
Ferri, E ;
Talarico, S ;
Di Giammarino, L ;
Carella, R ;
D'Errico, A ;
Spinosa, M ;
Spagnuolo, P ;
Bernardi, M .
JOURNAL OF HEPATOLOGY, 2000, 32 :115-115
[2]  
[Anonymous], 1999, J Hepatol, V30, P956
[3]   Triple antiviral therapy as a new option for patients with interferon nonresponsive chronic hepatitis C [J].
Brillanti, S ;
Levantesi, F ;
Masi, L ;
Foli, M ;
Bolondi, L .
HEPATOLOGY, 2000, 32 (03) :630-634
[4]   Chronic hepatitis C:: Interferon retreatment of relapsers.: A meta-analysis of individual patient data [J].
Cammà, C ;
Giunta, M ;
Chemello, L ;
Alberti, A ;
Toyoda, H ;
Trepo, C ;
Marcellin, P ;
Zahm, F ;
Schalm, S ;
Craxi, A .
HEPATOLOGY, 1999, 30 (03) :801-807
[5]  
Cammà C, 1999, AM J GASTROENTEROL, V94, P581, DOI 10.1111/j.1572-0241.1999.00919.x
[6]   Long-term course of interferon-treated chronic hepatitis C [J].
Cammà, C ;
Di Marco, V ;
Lo Iacono, O ;
Almasio, P ;
Giunta, M ;
Fuschi, P ;
Vaccaro, A ;
Fabiano, C ;
Magrin, S ;
Di Stefano, R ;
Bonura, C ;
Pagliaro, L ;
Craxì, A .
JOURNAL OF HEPATOLOGY, 1998, 28 (04) :531-537
[7]   Interferon and ribavirin for patients with chronic hepatitis C who did not respond to previous interferon therapy: A meta-analysis of controlled and uncontrolled trials [J].
Cheng, SJ ;
Bonis, PAL ;
Lau, J ;
Pham, NQ ;
Wong, JB .
HEPATOLOGY, 2001, 33 (01) :231-240
[8]   Definition of response to antiviral therapy in chronic hepatitis C [J].
Craxï, A ;
Cammà, C ;
Giunta, M .
JOURNAL OF HEPATOLOGY, 1999, 31 :160-167
[9]   Interferon and ribavirin vs interferon alone in the re-treatment of chronic hepatitis C previously nonresponsive to interferon - A meta-analysis of randomized trials [J].
Cummings, KJ ;
Lee, SM ;
West, ES ;
Cid-Ruzafa, J ;
Fein, SG ;
Aoki, Y ;
Sulkowski, MS ;
Goodman, SN .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 285 (02) :193-199
[10]   Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C [J].
Davis, GL ;
Esteban-Mur, R ;
Rustgi, V ;
Hoefs, J ;
Gordon, SC ;
Trepo, C ;
Shiffman, ML ;
Zeuzem, S ;
Craxi, A ;
Ling, MH ;
Albrecht, J .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (21) :1493-1499