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Monoterapia con ribavirina para la hepatitis C crónica

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References

Referencias de los estudios incluidos en esta revisión

Bodenheimer 1997 {published data only}

Bodenheimer HC, Lindsay KL, Davis GL, Lewis JH, Thung SN, Mahaney K, et al. Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C (abstract). Hepatology 1994;20(4 Pt 2):207A.
Bodenheimer HC, Lindsay KL, Davis GL, Lewis JH, Thung SN, Seeff LB. Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial. Hepatology 1997;26(2):473‐7. [MEDLINE: 97394443; PMID: 9252161]
Fiel MI, Guido M, Thung SN, Lindsay KL, Davis GL, Lewis JH, et al. Hepatic iron deposition during ribavirin therapy of chronic hepatitis C (abstract). Hepatology 1997;22(4 Pt 2):290A.
Fiel MI, Schiano TD, Guido M, Thung SN, Lindsay KL, Davis GL, et al. Increased hepatic iron deposition resulting from treatment of chronic hepatitis C with ribavirin. American Journal of Clinical Pathology 2000;113(1):35‐9. [PMID: 10631856, UI: 20097474]

Buti 1991 {published data only}

Buti M, Esteban R, Rodriguez‐Frias F, Jardi R, Guardia J. Ribavirin therapy for chronic type C hepatitis (abstract). Journal of Hepatology1991; Vol. 13, issue 2 Suppl:103S.

Chemello 1995 {published data only}

Chemello L, Cavalletto L, Bernardinello E, Guido M, Pontisso P, Alberti A. The effect of interferon alfa and ribavirin combination therapy in naive patients with chronic hepatitis C. Journal of Hepatology 1995;23(Suppl 2):8‐12. [MEDLINE: 96351137; PMID: 8720287]
Chemello L, Cavalletto L, Bernardinello E, Silvestri E, Benvegnu L, Pontisso P, et al. Response to ribavirin, to interferon and to a combination of both in patients with chronic hepatitis C and its relation to HCV genotypes. Journal of Hepatology 1994;21(Suppl 1):S12.

Di Bisceglie 1995b {published data only}

Di Bisceglie AM, Conjeevaram HS, Fried MW, Sallie R, Park Y, Yurdaydin C, et al. Ribavirin as therapy for chronic hepatitis C. A randomized, double‐blind, placebo‐controlled trial. Annals of Internal Medicine 1995;15(123):12.

Dusheiko 1996 {published data only}

Dusheiko G, Main J, Thomas H, Reichard O, Lee C, Dhillon A, et al. Ribavirin treatment for patients with chronic hepatitis C: results of a placebo‐controlled study. Journal of Hepatology 1996;25(5):591‐8. [MEDLINE: 97092970; PMID: 8938532]
Dusheiko G, Weiland O, Thomas H, Reichard O, Lee C, Dhillon A, et al. Results of a placebo‐controlled study of ribavirin in patients with chronic hepatitis C. Hepatology 1994;20(4 Pt 2):206A.

Felipe 2000 {published data only}

Felipe M, Silva EA, Lopes EP, Figueiredo VM, Cruz CN, Oliveira PM, et al. A prospective and randomised study using ribavirin as monotherapy for the treatment of naive patients with chronic hepatitis C. Brazilian Journal of Infectious Diseases 2000;4(4):183‐91.

Gonzalez‐Peralt 1997 {published data only}

Gonzalez‐Peralta RP, Liu WZ, Davis GL, Qian KP, Lau JY. Modulation of hepatitis C virus quasispecies heterogeneity by interferon‐alpha and ribavirin therapy. Journal of Viral Hepatitis 1997;4(2):99‐106. [MEDLINE: 97251583; PMID: 9097265]

Hoofnagle 2003 {published data only}

Hoofnagle JH, Ghany MG, Kleiner DE, Doo E, Heller T, Promrat K, et al. Maintenance therapy with ribavirin in patients with chronic hepatitis C who fail to respond to combination therapy with interferon alfa and ribavirin. Hepatology 2003;38(1):66‐74.

Kakumu 1993b {published data only}

Kakumu S, Yoshioka K, Ishikawa T, Higashi Y, Yamada M, Takayanagi M, et al. Ribavirin and IFN‐beta treatment for chronic hepatitis C (abstract). Hepatology 1992;16(2 Pt 2):68A.
Kakumu S, Yoshioka K, Wakita, Ishikawa T, Takayanagi M, Yasuyuki H. A pilot study of ribavirin and interferon beta for the treatment of chronic hepatitis C. Gastroenterology 1993;105:507‐12.

Khakoo 1998 {published data only}

Khakoo S, Glue P, Grellier L, Wells B, Bell A, Dash C, et al. Ribavirin and interferon alfa‐2b in chronic hepatitis C: assessment of possible pharmacokinetic and pharmacodynamic interactions. British Journal of Clinical Pharmacology 1998;46(6):563‐70. [MEDLINE: 99077061; PMID: 9862245]

Pawlotsky 2004 {published data only}

Castéra L, Germanidis G, Frainais PO, Hézole C, Dhumeaux D, Pawlotsky JM. Early changes in HCV hypervariable region 1 (HVR1) and non structural (NS) 5A gene quasispecies during interferon (IFN)‐alpha or ribavirin treatment: clues to the mechanisms of HCV resistance to antiviral therapy (abstract). Hepatology 1998;28(4 Pt 2):288A.
Pawlotsky JM, Dahan H, Conrad A, Lonjon I, Hézole C, Germanidis G, et al. Effect of intermittent interferon (IFN), daily IFN and IFN plus ribavirin induction therapy on hepatitis C virus (HCV) genotype 1b replication kinetics and clearance (abstract). Hepatology 1998;28(4 Pt 2):288A.
Pawlotsky JM, Dahari H, Neumann AU, Hezode C, Germanidis G, Lonjon I, et al. Antiviral action of ribavirin in chronic hepatitis C. Gastroenterology 2004;126(3):703‐14.

Sostegni 1998 {published data only}

Sostegni R, Ghisetti V, Pittaluga F, Marchiaro G, Rocca G, Borghesio E, et al. Sequential versus concomitant administration of ribavirin and interferon alfa‐n3 in patients with chronic hepatitis C not responding to interferon alone: results of a randomized, controlled trial. Hepatology 1998;28(2):341‐6. [MEDLINE: 98359166; PMID: 9695995]

Stanimirovic 2002 {published data only}

Stanimirovic V, Nikolic D, Stanimirovic B, Nikolic A, Cucak S. Evaluation of ribavirin efficacy and tolerance in subjects with chronic hepatitis C virus infection. Vojnosanitetski Pregled 2002;59(5):479‐84.

Veldt 2003 {published data only}

Veldt BJ, Brouwer JT, Adler M, Nevens F, Michielsen P, Delwaide J, et al. Retreatment of hepatitis C non‐responsive to interferon. A placebo controlled randomized trial of ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux. BMC Gastroenterology 2003;3(1):24.

Referencias de los estudios excluidos de esta revisión

Abergel 1999 {published data only}

Abergel A, Bonny C, Henquell C, Aublet‐Cuvelier B, Ughetto S, Martineau N, et al. Treatment of severe hepatitis C: interferon + ribavirine vs interferon (abstract). Hepatology 1999;30(4 Pt 2):267A.

Adinolfi 2000 {published data only}

Adinolfi LE, Tonziello A, Utili R, Andreana A, Marracino M, Sarnataro G, et al. High response rates to interferon induction plus ribavirin and amantadine in the treatment of interferon nonresponder chronic hepatitis C patients: a randomized controlled pilot study (abstract). Journal of Hepatology 2000;32(2 Suppl):107S.

Andreone 1999a {published data only}

Andreone P, Cursaro C, Gramenzi A, Fiorino S, di Giammarino L, Miniero R, et al. Interferon alpha plus ketoprofen or interferon alpha plus ribavirin in chronic hepatitis C non‐responder to interferon alpha alone: results of a pilot study. Italian Journal of Gastroenterology and Hepatology 1999;31(8):688‐94. [MEDLINE: 20192804]

Andreone 1999b {published data only}

Andreone P, Gramenzi A, Cursaro C, Sbolli G, Fiorino S, di Giammarino L, et al. Interferon‐alpha plus ribavirin in chronic hepatitis C resistant to previous interferon‐alpha course: results of a randomized multicenter trial. Journal of Hepatology 1999;30(5):788‐93. [MEDLINE: 99291925; PMID: 10365803]

Andreone 2000 {published data only}

Andreone P, Cursaro C, Gramenzi A, Margotti M, Ferri E, Talarico S, et al. High dose of interferon a (IFN) plus ribavirin (RIBA) for 6 or 12 months in non responder (NR) patients with chronic hepatitis C (CHC): Results of a randomized trial. Journal of Hepatology 2000;32(2 Suppl):115S.

Antignano 1999 {published data only}

Antignano LV, Wu GU, Krawitt EL, Kimby AE, Malamood HS, Notis W, et al. Preliminary results of a nynest interferon‐ribavirin treatment trial in chronic hepatitis C patients not previously treated with interferon (abstract). Hepatology 1999;30(4 Pt 2):635A.

Ascione 1998 {published data only}

Ascione A, de Luca M, Guardascione MA, Canestrini C, Galeota Lanza A, Astritto S, et al. Interferon plus ribavirin vs interferon alone in HCV chronic liver disease non responder to a previous cycle of interferon alone (abstract). Journal of Hepatology 1998;28(1 Suppl):198S.

Bacon 1998 {published data only}

Bacon BR, Rauscher JA, Amith‐Wilkaitis NL, Randall DC, Koehler KM, Di Bisceglie AM. Interferon‐ribavirin combination is successful in eliminating hepatitis C virus in non‐responders to interferon alone including patients with normal aminotransferases (abstract). Hepatology 1998;28(4 Pt 2):372A.

Bailey 1997 {published data only}

Bailey RJ, Meyer DL. A preliminary study of short course of ribavirin and alpha interferon in treatment of chronic active hepatitis C not responding to alpha interferon alone (abstract). Hepatology 1997;26(4 Pt 2):476A.

Baracetti 2000 {published data only}

Baracetti S, Colle R, Gregotti M, Nascimben F, Virgilli F, Zorat F, et al. Randomized trial of combination therapy in relapser or non‐responder HCV patients (abstract). Journal of Hepatology 2000;32(2 Suppl):107S.

Barbaro 1998a {published data only}

Barbaro G, Di Lorenzo G, Soldini M, Giancaspro G, Bellomo G, Belloni G, et al. Interferon‐alpha‐2B and ribavirin in combination for chronic hepatitis C patients not responding to interferon‐alpha alone: an Italian multicenter, randomized, controlled, clinical study. American Jounal of Gastroenterology 1998;93(12):2445‐51. [MEDLINE: 99075750; PMID: 9860407]

Barbaro 1998b {published data only}

Barbaro G, Belloni G, Ferrari L, Di Lorenzo G, Soldini M, Giancaspro G, et al. Alpha interferon 2b plus ribavirin in CHC relapser or not responder patients to alpha interferon 2b alone: an Italian multicenter randomized controlled clinical study (abstract). Hepatology 1998;28(4 Pt 2):476A.

Barbaro 1999 {published data only}

Barbaro G, Di Lorenzo G, Belloni G, Ferrari L, Paiano A, Del Poggio P, et al. Interferon alpha‐2B and ribavirin in combination for patients with chronic hepatitis C who failed to respond to, or relapsed after, interferon alpha therapy: a randomized trial. American Journal of Medicine 1999;107(2):112‐8. [MEDLINE: 99387796; PMID: 10460040]

Barbaro 2000a {published data only}

Barbaro G, Di Lorenzo G, Soldini M, Giancaspro G, Pellicelli A, Grisorio B, et al. Evaluation of efficacy of interferon alpha‐2b and ribavirin in combination in naive patients with chronic hepatitis C: an Italian multicenter experience. Journal of Hepatology 2000;33:448‐55.

Bekkering 2000 {published data only}

Bekkering FC, Hansen BE, Brouwer JT, Niesters HGM, Schalm SW. Effect of daily versus twice daily high dose IFN and ribavirin treatment on HCV kinetics (abstract). Journal of Hepatology 2000;32(2 Suppl):101S.

Bell 1999 {published data only}

Bell H, Hellum K, Harthug S, Myrvang B, Ritland S, Maeland A, et al. Treatment with interferon‐alpha2a alone or interferon‐alpha2a plus ribavirin in patients with chronic hepatitis C previously treated with interferon‐alpha2a. Scandinavian Journal of Gastroenterology 1999;34(2):194‐8. [MEDLINE: 99401091; PMID: 10470088]

Belli 2001 {published data only}

Belli LS, Alberti AB, Rondinara GF, de Carlis L, Corti A, Mazza E, et al. Early ribavirin treatment and avoidance of corticosteroids in hepatitis C virus (HCV)‐positive liver transplant recipients: interim report of a prospective randomized trial. Transplantation Proceedings 2001;33(1‐2):1353‐4.

Bellobouno 1997 {published data only}

Bellobuono A, Mondazzi L, Tempini S, Silini E, Vicari F, Idéo G. Ribavirin and interferon‐alpha combination therapy vs interferon‐alpha alone in the retreatment of chronic hepatitis C: a randomized clinical trial. Journal of Viral Hepatitis 1997;4(3):185‐91. [MEDLINE: 97325474; PMID: 9181527]

Bellobouno 1998 {published data only}

Bellobuono A, Tempini S, Mondazzi L, di Napoli M, Idéo G. Twelve month combination treatment with ribavirin and alpha IFN in patients affected by chronic hepatitis C unresponsive to alpha IFN: comparison of three different schedules (abstract). Hepatology 1998;28(4 Pt 2):479A.

Bellobouno 1999 {published data only}

Bellobuono A, Tempini S, Mondazzi L, Brasca P, Marino F, Ideo G. Twelve month retreatment with IFN and ribavirin or IFN alone in relapser patients with chronic hepatitis C (abstract). Hepatology 1999;30(4 Pt 2):263A.

Bellobuono 1995 {published data only}

Bellobuono A, Tempini S, Bellati G, Asti L, Ideo G. Ribavirin followed by alpha interferon in chronic hepatitis C resistant to therapy (abstract). Gastroenterology 1995;108(4 Suppl):1033S.

Bellobuono 2000a {published data only}

Bellobuono A, Mondazzi L, Tempini S, Chiodo F, Magliano E, Furione L, et al. Early addition of ribavirin to interferon in chronic hepatitis C not responsive to interferon monotherapy. Journal of Hepatology 2000;33:463‐8.

Bellobuono 2000b {published data only}

Bellobbuono A, Tempini S, Grimoldi D, Idéo GM, Mondazzi L, Brasca P, et al. Effect of 12 month aIFN and ribavirin combination therapy in chronic hepatitis C unresponsive to aIFN (abstract). Journal of Hepatology 2000;32(2 Suppl):178S.

Bellobuono 2000c {published data only}

Bellobuono A, Tempini S, Idèo GM, Brasca P, Mondazzi L, Antonelli G, et al. aIFN and ribavirin combination therapy reduces the occurrence of breakthrough in chronic hepatitis C (abstract). Journal of Hepatology 2000;32(Suppl 2):111.

Benetti 2001 {published data only}

Benetti G, Ramella G, Tagger A, Ribero ML, Tortora M, Borzio M, et al. IFN alpha 2B and ribavirin in naive patients with HCV type 1 chronic hepatitis: results after 6 months threapy (abstract). Journal of Hepatology 2001;34(1):357A.

Benhamou 2007 {published data only}

Benhamou Y, Pockros P, Rodriguez‐Torres M, Gordon S, Shiffman M, Lurie Y, et al. The safety and efficacy of viramidine plus PegIFN alfa‐2b versus ribavirin plus PegIFN alfa‐2b in therapy naive patients infected with HCV: phase 3 results (VISER1) (abstract). Journal of hepatology2007; Vol. 44:273.

Berg 2000a {published data only}

Berg T, Hoffmann RM, Teuber G, Leifeld L, Lafrenz M, Baumgarten R, et al. Efficacy of a short‐term ribavirin plus interferon alfa combination therapy followed by interferon alfa alone in previously untreated patients with chronic hepatitis C: a randomized multicenter trial. Liver International 2000;20(6):427‐36.

Berg 2000b {published data only}

Berg T, Naumann U, Wiedenmann B, Hopf U. Kinetics of hepatitis C viremia in interferon plus ribavirin treated patients (abstract). Hepatology 1998;28(4 Pt 2):373A.

Bernatik 2000 {published data only}

Bernatik T, Klinker H, Scheurlen M, Meyer H, Norgauer W, Rambach W, et al. Interferon/ribavirin combination therapy with and without daily dosing in retreatment of chronic hepatitis C (abstract). Journal of Hepatology 2000;32(Suppl 2):187.

Bernstein 1998 {published data only}

Bernstein DE, Khan R, Jeffers LJ, Reddy KR, Schiff ER. Low dose ribavirin (RBV) in combination interferon (IFN) for the treatment of hepatitis C non‐responder and relapse patients (abstract). Hepatology1998; Vol. 28, issue 4 Pt 2:702A.

Bjøro 2000 {published data only}

Bjøro K, Bell H, Hellum KB, Myrvang B, Skaug K. Rapid viral clearance with IFN‐a 2b induction therapy and ribavirin for chronic HCV infection (abstract). Journal of Hepatology 2000;32(2 Suppl):38S.

Bresci 2000 {published data only}

Bresci G, Parisi G, Bertoni M, Scatena F, Capria A. Interferon plus ribavirin in chronic hepatitis C non‐responders to recombinant alpha‐interferon. Journal of Viral Hepatitis 2000;7(1):75‐81.

Brillanti 1995 {published data only}

Brillanti S, Foli M, Masci C, Miglioli M. Three‐year follow‐up of chronic hepatitis C patients treated with ribavirin plus interferon‐alpha combination therapy: evidence for long‐term efficacy and safety (abstract). Hepatology 1996;24(4 Pt 2):395A.

Brillanti 1999 {published data only}

Brillanti S, Foli M, Di Tomaso M, Gramantieri L, Masci C, Bolondi L. Pilot study of triple antiviral therapy for chronic hepatitis C in interferon alpha non‐responders. Italian Journal of Gastroenterology and Hepatology 1999;31(2):130‐4. [MEDLINE: 99291377; PMID: 10363198]

Brouwer 2001 {published data only}

Brouwer JT, Hansen BE, Schalm SW. Low relapse rate in chronic hepatitis C treated with 18 months interferon‐alpha and ribavirin as compared to 6 months combination therapy and to 18 months monotherapy. A Benelux study in 300 patients (abstract). Journal of Hepatology 2000;32(4 Pt 2):592A.

Bugliescu 2000 {published data only}

Bugliescu L, Cojocaru L, Micu L, Copaci I. Results of associated treatment with interferon (IFN) + ribavirin in HCV active chronic hepatitis (abstract). Journal of Gastroenterology and Hepatology 2000;15(Suppl):F83.

Calanca 2007 {published data only}

Calanca LN, Fehr T, Jochum W, Fischer‐Vetter J, Müllhaupt B, Wüthrich RP, et al. Combination therapy with ribavirin and amantadine in renal transplant patients with chronic hepatitis C virus infection is not superior to ribavirin alone. Journal of Clinical Virology 2007;39(1):54‐8.

Camps 1993 {published data only}

Camps J, Garcia N, Riezu BJ, Civeira MP, Prieto J. Ribavirin in the treatment of chronic hepatitis C unresponsive to alfa interferon. Journal of Hepatology 1993;19(3):408‐12. [MEDLINE: 94201541; PMID: 8151102]

Caremani 1996 {published data only}

Caremani M, Benci A, Castellacci R, Tacconi D. A randomised controlled trial of leukocyte IFN‐alpha+ribavirin in HCV chronic hepatitis relapsing patients (abstract). Hepatology 1996;24(4 Pt 2):395A. [CN‐00186171]

Cattral 1999 {published data only}

Cattral MS, Hemming AW, Wanless IR, Al‐Ashgar H, Krajden M, Lilly L, et al. Outcome of long‐term ribavirin therapy for recurrent hepatitis C after liver transplantation. Transplantation 1999;67(9):1277‐80. [MEDLINE: 99271750; PMID: 10342322]

Cavaletto 2000 {published data only}

Cavalletto L, Chemello L, Donada C, Casarin P, Belussi F, Bernardinello E, et al. The pattern of response to interferon alpha (alpha‐IFN) predicts sustained response to a 6‐month alpha‐IFN and ribavirin retreatment for chronic hepatitis C. TVVH Study Group. Journal of Hepatology 2000;33(1):128‐34. [MEDLINE: PMID: 10905596, UI: 20361531]

Chapman 2001 {published data only}

Chapman BA, Stace NH, Edgar CL, Bartlett SE, Frampton CMA, Scahill SL, et al. Interferon‐alpha 2a/Ribavirin versus interferon‐alpha 2a alone for the retreatment of hepatitis C patients who relapse after standard course of interferon. New Zealand Medical Journal 2001;114(1128):103‐4.

Cheinquer 1998 {published data only}

Cheinquer H, Coelho‐Borges S, Cheinquer N, Lunge V, Ikuta N, Fonseca A. Sustained response in chronic hepatitis C patients after six months of interferon or interferon and ribavirin (abstract). Hepatology 1998;28(4 Pt 2):477A.

Colantoni 2000 {published data only}

Colantoni A, De Maria N, Idilman R, Harig J, Van Thiel DH. Racial differences in the response to antiviral therapy for chronic hepatitis C (abstract). Journal of Hepatology 2000;32(2 Suppl):194S.

Davis 1998 {published data only}

Davis GL, Esteban‐Mur R, Rustgi V, Hoefs J, Gordon SC, Trepo C, et al. Interferon alfa‐2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. New England Journal of Medicine 1998;339(21):1493‐9. [MEDLINE: UI: 99025347; PMID: 9819447]

De Bac 1998 {published data only}

De Bac C, Pastores G, Piccinino F, Badolato MC, Tosti ME, Osso A, et al. Ribavirin and interferon retreatment of HCV chronic patients non responder to interferon (abstract). Journal of Hepatology 1998;28(Suppl 1):123.

De Franceschi 2000 {published data only}

De Franceschi L, Fattovich G, Turrini F, Ayi K, Brugnara C, Manzato F, et al. Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitis C virus infection: role of membrane oxidative damage. Hepatology 2000;31(4):997‐1004. [MEDLINE: 20198173; PMID: 10733558]

Dettmer 2002 {published data only}

Dettmer R, Reinus JF, Clain DJ, Aytaman A, Levendoglu H, Bloom AA, et al. Interferon‐alpha‐2b for retreatment of chronic hepatitis C. Hepatogastroenterology 2002;49:758‐63.

Di Bisceglie 1992 {published data only}

Di Bisceglie AM, Hoofnagle JH, Krawczynski K. Changes in hepatitis C virus antigen in liver with antiviral therapy. Gastroenterology 1993;105(3):858‐62. [MEDLINE: 93366134; PMID: 7689520]

Di Bisceglie 1995 {published data only}

Di Biscleglie AM, Fried MW, Swain MG, Bergasa NV, Yurdaydin C, Simpson LH, et al. Randomized, double blind placebo‐controlled trial of ribavirin therapy for chronic hepatitis C (abstract). Hepatology 1993;18(4 Pt 2):93A.

Di Marco 2000 {published data only}

Di Marco V, Almasio P, Vaccaro A, Ferraro D, Parisi P, Cataldo GM, et al. Combined treatment of relapse of chronic hepatitis C with high‐dose alpha2B interferon plus ribavirin for 6 or 12 months. Journal of Hepatology 2000;33:456‐62.

Ehardt 2000 {published data only}

Erhardt A, Maschner‐Olberg A, Häussinger D. Treatment with interferon‐a and ribavirin in patients with chronic hepatitis C and persistently normal ALT levels (abstract). Journal of Hepatology 2000;32(2 Suppl):183S.

el‐Zayadi 1999 {published data only}

el‐Zayadi A, Selim O, Hadda S, Simmmonds C, Hamdy H, Badran HM, et al. Combination treatment of interferon alpha‐2b and ribavirin in comparison to interferon monotherapy in treatment of chronic hepatitis C genotype 4 patients. Italian Journal of Gastroenterology and Hepatology 1999;31(6):472‐5.

Ersöz 2000 {published data only}

Ersöz G, Akarca US, Günsar F, Vardar R, Karasu Z, Batur Y. IFN‐ribavirin combination therapy for patients with HCV‐related decompensated cirrhosis (abstract). Journal of Hepatology 2000;32(Suppl 2):193.

Feher 2000 {published data only}

Feher JLG, Bàlint T. The efficacy of combined interferon‐alfa‐2B and ribavirin therapy in patients with chronic hepatitis C. Final reports of a multicenter study with 100 patients in Hungary (abstract). Journal of Hepatology 2000;32(Suppl 2):202.

Ferenci 2000 {published data only}

Ferenci P, Brunner H, Vogel W, Gschwantler M, Datz Ch, Hackl F, et al. Interferon (IFN) induction therapy in combination with ribavirin in chronic hepatitis C (abstract). Journal of Hepatology 2000;32(Suppl 2):38.

Ferenci 2001 {published data only}

Ferenci P, Stauber R, Steindl‐Mundi P, Gschwantler M, Fickert P, Datz C, et al. Treatment of patients with chronic hepatitis C not responding to interferon with high‐dose interferon alpha with or without ribavirin: final results of a prospective randomised trial. European Journal of Gastroenterology and Hepatology 2001;13(6):699‐705.

Fraquelli 2000 {published data only}

Fraquelli M, Conte D, Prati D, Colucci A, Minola E. Chronic HCV infection in pregnant women (abstract). Journal of Hepatology 2000;32(2 Suppl):177S.

Gallego 2000 {published data only}

Gallego A, Garcia‐Samaniego J, Diago M, Pérez‐Olmeda M, Valeros MD, Enriquez J. Retreatment with IFN alfa 2B + ribavirin (24 vs 48 weeks) for patients with chronic hepatitis C who relapsed or did not respond to IFN alone (abstract). Journal of Hepatology 2000;32(2 Suppl):107S.

Gane 1998 {published data only}

Gane EJ, Lo SK, Riordan SM, Portmann BC, Lau JY, Naoumov NV, et al. A randomized study comparing ribavirin and interferon alfa monotherapy for hepatitis C recurrence after liver transplantation. Hepatology 1998;27(5):1403‐7. [MEDLINE: 98240830; PMID: 9581698]

Garnier 1997 {published data only}

Garnier JL, Chevallier P, Dubernard JM, Trepo C, Touraine JL, Chossegros P. Treatment of hepatitis C virus infection with ribavirin in kidney transplant patients. Transplantation Proceedings 1997;29(1‐2):783.

Gerotto 1999 {published data only}

Gerotto M, Sullivan DG, Polyak SJ, Chemello L, Cavalletto L, Pontisso P, et al. Effect of retreatment with interferon alone or interferon plus ribavirin on hepatitis C virus quasispecies diversification in nonresponder patients with chronic hepatitis C. Journal of Virology 1999;73(9):7241‐7.

Gish 1998 {published data only}

Gish R, Yao F, Brooks L, Poordad G, Schulze G. A randomized trial of interferon alfa‐2b, daily vs. three times a week for one month, followed by three times a week for one year in combination with ribavirin in patients who have failed a previous course of interferon (abstract). Hepatology 1998;28(4 Pt 2):574A.

Gish 2007 {published data only}

Gish RG, Arora S, Rajender Reddy K, Nelson DR, O'Brien C, Xu Y, et al. Virological response and safety outcomes in therapy‐naive patients treated for chronic hepatitis C with taribavirin or ribavirin in combination with pegylated interferon alfa‐2a: a randomized, phase 2 study. Journal of Hepatology 2007;47(1):51‐9.

Glue 2000 {published data only}

Glue P, Rouzier‐Panis R, Raffanel C, Sabo R, Gupta SK, Salfi M, et al. A dose‐ranging study of pegylated interferon alfa‐2b and ribavirin in chronic hepatitis C. Hepatology 2000;32(3):647‐53.

Gross 1999a {published data only}

Gross JB, Lindor KD, Abdelmalek MF, Poterucha JJ, Brandhagen DJ, Czaja AJ, et al. Interferon alpha 2b 5MU tiw with or without ribavirin as initial treatment for hepatitis C (abstract). Hepatology 1999;30(4 Pt 2):634A.

Gross 1999b {published data only}

Gross JB, Lindor KD, Abdelmalek MF, Poterucha JJ, Brandhagen DJ, Czaja AJ, et al. Interferon alpha 2b 5MIU tiw, +/‐ 4‐week daily interferon induction, +/‐ ribavirin, for re‐treatment of interferon non‐responders with chronic hepatitis C (abstract). Hepatology 1999;30(4 Pt 2):634A.

Götz 1998 {published data only}

Götz G, Schön MR, Haefker A, Neuhaus R, Berg T, Hopf U, et al. Treatment of recurrent hepatitis C virus infection after liver transplantation with interferon and ribavirin. Transplantion Proceedings 1998;30(5):2104‐6. [MEDLINE: 98390849; PMID: 9723407]

Harris 2000 {published data only}

Harris HE, Ramsay MEB, Elridge KP. Signs and symptoms of liver disease after 10 years of infection with hepatitis C virus. Data from a national cohort of patients who acquired their infections on a known date (abstract). Journal of Hepatology 2000;32(2 Suppl):98S.

Herrine 1998 {published data only}

Herrine SK, Conn MI, Greenfield SM, Shaw EW, Thornton JJ, Weinberg DS. Interferon alpha‐2b and ribavirin for non‐responding and relapsing chronic hepatitis C ‐ an interim analysis (abstract). Hepatology 1998;28(4 Pt 2):578A.

Junqing 1996 {published data only}

Junqing Yi, Wanfen Wu, Daozhen Xu, Wenbin D, Yongjun Xu, Xinger L. Histologic observation on intron and ribavirin in the treatment of 22 patients with chronic hepatitis C (abstract). Chinese Journal of Infectious Diseases 1996;14(3 Suppl):179S‐180S.

Juszezyk 2000 {published data only}

Juszezyk J, Bolewska B, Cianciara J, Jablonska J, Zaborowski P, Niedzialek D, et al. Combination therapy with interferon alpha‐2B and ribavirin in naive patients with chronic hepatitis C (abstract). Journal of Hepatology 2000;32(2 Suppl):199S.

Kallinowski 1999 {published data only}

Kallinowski B, Jakob B, Schwake L, Stremmel W. Interferon and ribavirin for the treatment of relapse and nonresponse of chronic hepatitis C (abstract). Journal of Hepatology 1999;30(1 Suppl):245S.

Katsarou 2000 {published data only}

Katsarou O, Gialeraki A, Loukopoulou H, Hatzakis A, Karafoulidou A. Combination treatment with interferon (IFN) and ribavirin (RBV) in HCV (+) HIV (‐) haemophilia Pts., non responders (NR) to IFN monotherapy (abstract). Journal of Hepatology 2000;32(2 Suppl):189S.

Koshy 2000 {published data only}

Koshy A, Marcellin P, Martinot M, Madda JP. Improved response to ribavirin interferon combination compared with interferon alone in patients with type 4 chronic hepatitis C without cirrhosis. Liver International 2000;20(4):335‐9.

Lai 1996 {published data only}

Lai MY, Kao JH, Yang PM, Wang JT, Chen PJ, Chan KW, et al. Long‐term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C. Gastroenterology 1996;111(5):1307‐12. [MEDLINE: 97054348; PMID: 8898645]

Lee 1998 {published data only}

Lee JH, von Wagner M, Roth WK, Teuber G, Sarrazin C, Zeuzem S. Effect of ribavirin on virus load and quasispecies distribution in patients. Journal of Hepatology 1998;29(1):29‐35. [MEDLINE: 98359678; PMID: 9696489]

Lin 2004 {published data only}

Lin C‐C, Xu C, Teng A, Yeh L‐T, Peterson J. Dosing with viramidine in HCV patients resulted in lower plasma and RBC ribavirin levels and exhibited smaller decreases in hemoglobin compared to ribavirin dosing (abstract). Hepatology2004; Vol. 40, issue 4 (Suppl 1):386.

Lédinghen 2002a {published data only}

Lédinghen V, Trimoulet P, Winnock M, Foucher J, Bourliére M, Desmorat H, et al. Daily or three times a week interferon alfa‐2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis. Journal of Hepatatology 2002;36:672‐80.

Lédinghen 2002b {published data only}

Lédinghen VL, Trimoulet P, Bernard PH, Bourliere M, Portal I, Rémy AJ, et al. Daily or three times per week interferon alpha‐2b combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C not responding to previous interferon alone. Journal of Hepatology 2002;36(6):819‐26.

Malik 2002 {published data only}

Malik AH, Kumar KS, Malet PF, Ostapowicz G, Adams G, Wood M, et al. A randomised trial of high‐dose interferon alpha‐2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon. Alimentary Pharmacology & Therapeutics 2002;16(3):381‐8.

Mangia 2001 {published data only}

Mangia A, Villani MR, Minerva N, Leandro G, Bacca D, Cela M, et al. Efficacy of 5 MU of interferon in combination with ribavirin for naive patients with chronic hepatitis C virus: a randomised controlled trial. Jornal of Hepatology 2001;34:441‐6.

Marcellin 1999 {published data only}

Marcellin P, Hezode C, Castelnau C, Barange K, Couzigou P, Larrey D, et al. Randomized controlled trial of combination therapy with interferon (IFN) alfa‐2A and ribavirin, in patients with chronic hepatitis C who relapsed after interferon therapy (abstract). Hepatology 1999;30(4 Pt 2):192A.

Marco 2000 {published data only}

Marci VD, Almasio P, Vaccaro A, Ferraro D, Parisi P, Cataldo MG, et al. Combined treatment of relapse of chronic hepatitis C with high‐dose alpha‐2b interferon plus ribavirin for 6 or 12 months. Journal of Hepatology 2000;33(3):456‐62.

Marco 2002 {published data only}

Marco DV, Ferraro D, Almasio P, Vaccaro A, Parisi P, Cappello M, et al. Early viral clearance and sustained response in chronic hepatitis C: a controlled trial of interferon and ribavirin after high‐dose interferon induction. Journal of Viral Hepatitis 2002;9(2):453‐9.

Mazzaferro 1997 {published data only}

Mazzaferro V, Regalia E, Pulvirenti A, Tagger A, Andreola S, Pasquali M, et al. Prophylaxis against HCV recurrence after liver transplantation: effect of interferon and ribavirin combination. Transplantation Proceedings 1997;29(1‐2):519‐21. [MEDLINE: 97230702; PMID: 9123113]

McHutchison 1998 {published data only}

McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, et al. Interferon alfa‐2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. New England Journal of Medicine 1998;339(21):1485‐92. [MEDLINE: 99025346; PMID: 9819446]

Menzel 2000 {published data only}

Menzel J, Ullerich HJ, Domschke W. A randomized pilot study in IFN‐naive patients comparing daily high‐dose interferon‐alpha (IFN 2A) triple therapy with tiw interferon‐alpha (IFN 2 A ) triple therapy ‐ first results (abstract). Journal of Hepatology 2000;32(2 Suppl):190S.

Milella 1999 {published data only}

Milella M, Santantonio T, Pietromatera G, Maselli R, Casalino C, Mariano N, et al. Retreatment of non‐responder or relapser chronic hepatitis C patients with interferon plus ribavirin vs interferon alone. Italian Journal of Gastroenterology and Hepatology 1999;31(3):211‐5.

Nagayama 2005 {published data only}

Nagayama R, Tanaka A, Ankoh H, Narita T, Izumi M, Miyake K, et al. Efficacy of ribavirin monotherapy following combination therapy with interferon alfa‐2b and ribavirin for patients with chronic hepatitis C. Hepatology Research 2005;32(2):101‐6.

Nunes 1999 {published data only}

Nunes DP, Anastopoulos H, Gordon F, Chopra S, Petruff C, Solomons H, et al. Double‐blind placebo controlled study of interferon versus interferon plus ribavirin for the treatment of hepatitis C in patients who previously failed interferon monotherapy (abstract). Hepatology 1999;30(4 Pt 2):199A.

Perasso 1999 {published data only}

Perasso A, Testino G, Ansaldi F, Venturino V, Icardi GC. r‐Interferon alfa‐2b/ribavirin combined therapy followed by low‐dose r‐interferon alfa‐2b in chronic hepatitis C interferon nonresponders. Hepatology 1999;29(1):297‐8. [MEDLINE: 99129321; PMID: 9935339]

Pol 1999 {published data only}

Pol S, Couzigou P, Bourlière M, Abergel A, Combis JM, Larrey D, et al. A randomized trial of ribavirin and interferon‐alpha vs. interferon‐alpha alone in patients with chronic hepatitis C who were non‐responders to a previous treatment. Multicenter Study Group under the coordination of the Necker Hospital, Paris, France. Journal of Hepatology 1999;31(1):1‐7. [MEDLINE: 99351563; PMID: 10424277]

Pol 2000a {published data only}

Pol S, Nalpas B, Bourlière M, Couzigou P, Tran A, Abergel A, et al. Combination of ribavirin and interferon‐alfa surpasses high doses of interferon‐alfa alone in patients with genotype 1b‐related chronic hepatitis. Hepatology 2000;31(6):1338‐44. [MEDLINE: 20287465; PMID: 10827161]

Poordad 2008 {published data only}

Poordad F, Lawitz E, Chun E, Hammond J. Treatment week 12 results of weight‐based taribavirin versus weight‐based ribavirin, both with peginterferon alfa‐2b, in naive chronic hepatitis C, genotype 1 patients (abstract). Journal of Hepatology2008; Vol. 48, issue Suppl 2:373.

Portal 2000 {published data only}

Portal‐Bartolomei I, Bourlière M, Halfon P, De Lédinghen V, Bernard P, Botti G, et al. Retreatment with interferon‐ribavirin according to viremia of interferon responder‐relapser patients: preliminary results of a prospective French multicenter randomized controlled study (abstract). Hepatology 1999;30(4 Pt 2):194A.

Poynard 1998a {published data only}

Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet 1998;352(9138):1426‐32. [MEDLINE: 99023142; PMID: 9807989]

Quadri 2000 {published data only}

Quadri R, Giostra E, Rubbia‐Brandt L, Mentha G, Malé PJ, Hadenque A, et al. Mechanism of action of ribavirin in treatment of recurrent hepatitis C after liver transplant (abstract). Journal of Hepatology 2000;32(2 Suppl):91S.

Reichard 1998 {published data only}

Reichard O, Norkrans G, Fryden A, Braconier JH, Sonnerborg A, Weiland O. Randomised, double‐blind, placebo‐controlled trial of interferon alpha‐2b with and without ribavirin for chronic hepatitis C. Lancet 1998;351(9096):83‐7. [MEDLINE: 98102664; PMID: 9439491]

Ricchiuti 1996 {published data only}

Ricchiuti A, Ciccorossi P, Costa F, Bellini M, Tumino E, Petruccelli S, et al. Combination therapy with interferon alpha and ribavirin in interferon alpha relapsers (abstract). Hepatology 1996;24(4 Pt 2):395A.

Ricchiuti 1999 {published data only}

Ricchiuti A, Ciccorossi P, Costa F, Bellini M, Da Massa Carara P, Arpe P, et al. Daily administration of interferon alpha 2b and utility of combination therapy with ribavirin as initial treatment for chronic hepatitis C (abstract). Hepatology 1999;30(4 Pt 2):627A.

Rosen 1999 {published data only}

Rosen HR, Miner C, Wolf SL, Portland VA, Portland OR, Gretch DR. A randomized trial of daily vs b.i.d. interferon induction followed by combination rebetron therapy for HCV genotype 1 infection (abstract). Hepatology 1999;30(4 Pt 2):192A.

Rothstein 1998 {published data only}

Rothstein K, Suvannasankha A, DiGregorio K, Gross F, Peikin S, Mushnick A, et al. Serum HCV RNA kinetics during combination therapy with daily interferon alpha and ribavirin (abstract). Hepatology 1998;28(4 Pt 2):706A.

Salmeron 1999 {published data only}

Salmeron J, Ruiz‐Extremera A, Torres C, Rodriguez‐Ramos L, Lavin I, Quintero D, et al. Interferon versus ribavirin plus interferon in chronic hepatitis C previously resistant to interferon: a randomized trial. Liver 1999;19(4):275‐80. [MEDLINE: 99387380; PMID: 10459624]

Sarin 1999 {published data only}

Sarin SK, Guptan RC, Thakur V. Efficacy of interferon alone or ribavirin interferon combination in HCV related cirrhosis and chronic hepatitis patients: a randomized controlled trial (abstract). Hepatology 1999;30(4 Pt 2):634A.

Scotto 1996 {published data only}

Scotto G, Fazio V, Tantimonaco G. Pilot study of a short course of ribavirin and alpha interferon in the treatment of chronic active hepatitis C not responding to alpha‐interferon alone. Italian Journal of Gastroenterology 1996;28(9):505‐11. [MEDLINE: 97278061; PMID: 9131395]

Shakil 1999 {published data only}

Shakil O, Rakela J. Interferon‐alpha2b and ribavirin combination therapy in liver transplant recipients with recurrent hepatitis C (abstract). Hepatology 1999;30(4 Pt 2):656A.

Sherif 1996 {published data only}

Sherif SMAF, Sobhy AA. Comparison of interferon, ribavirin and combined interferon with ribavirin in chronic hepatitis C with cirrhosis: an interim report (abstract). Hepatology 1996;23(1):176.

Shiffman 2000 {published data only}

Shiffman ML, Hofmann CM, Gabbay J, Luketic VA, Sterling RK, Sanyal AJ, et al. Treatment of chronic hepatitis C in patients who failed interferon monotherapy: effects of higher doses of interferon and ribavirin combination therapy. American Journal of Gastroenterology 2000;95(10):2982‐5.

Shiffman 2001 {published data only}

Hofmann CM, Sterling RK, Luketic VA, Contos MJ, Sanyal AJ, Shiffman ML. A Randomized, Controlled Trial to Determine if Continuing Ribavirin (Rvn) as Monotherapy Following Interferon/Ribavirin (Ifn/Rvn) Combination Therapy Will Increase Sustained Virologic Response in Patients With Chronic HCV (abstract). Gastroenterology 2000;118(4):219.
Shiffman ML, Hofmann CM, Sterling RK, Luketic VA, Contos MJ, Sanyal AJ. A randomized, controlled trial to determine whether continued ribavirin monotherapy in hepatitis C virus‐infected patients who responded to interferon‐ribavirin combination therapy will enhance sustained virologic response. Journal of Infectious Diseases 2001;184(4):405‐9.

Stalke 2000 {published data only}

Stalke P, Witczak‐Malinowska K, Lakomy E, Michalska Z, Dzierbicki A. Hematologic side effects of interferon alpha and ribavirin therapy of chronic active hepatitis C (abstract). Journal of Hepatology 2000;32(2 Suppl):204S.

Tassopoulos 1999 {published data only}

Tassopoulos NC, Tsantoulas D, Raptopilou M, Paraskevas E, Avregerinos A, Kantakis S, et al. Efficacy of interferon‐alpha 2b in combination with ribavirin in the treatment if non‐responder patients with chronic hepatitis C: a randomised‐controlled trial (abstract). Hepatology 1999;30(4 Pt 2):632A.

Teuber 2000 {published data only}

Teuber G, Berg T, Hoffmann RM, Leifeld L, Lafrenz M, Spengler U, et al. Retreatment with interferon‐alpha and ribavirin in primary interferon‐alpha non‐responders with chronic hepatitis C. Digestion 2000;61(2):90‐7. [MEDLINE: 20171249; PMID: 10705172]

Toccaceli 1997 {published data only}

Toccaceli F, Grimaldi M, Rosati S, Palazzini E, Laghi V. Ribavirin plus human leucocyte interferon alpha for the treatment of interferon resistant chronic hepatitis C: a controlled trial. Hepatology Research 1997;8(2):106‐12.

Tripi 1998 {published data only}

Tripi S, di Gaetano G, Cartabellotta F, Vassallo R, Soresi M, Carroccio A, et al. Ribavirin and alpha‐interferon in patients with chronic hepatitis C not responding to interferon alone (abstract). Journal of Hepatology 1998;28(1 Suppl):212S.

Verbaan 2002 {published data only}

Verbaan HP, Widell HEA, Bodeson TL, Lindgren SC. High sustained response rate in patients with histologically mild (low grade and stage) chronic hepatitis C infection. A randomised, double blind, placebo controlled trial of interferon alpha‐2b with or without ribavirin. European Journal of Gastroenterology and Hepatology 2002;14:627‐33.

Vogel 2002 {published data only}

Vogel W. Measurement of viral interferon sensitivity in patients with chronic hepatitis C. Prospective randomised, open label phase 3 clinical trial (abstract). Journal of Hepatology 2002;36(Suppl 1):135.

Wiese 2000a {published data only}

Wiese M, Berr F, Porst H, Lefrenz M, Oesen U. Low frequency of cirrhosis in a large hepatitis C outbreak after 20 years (abstract). Journal of Hepatology 2000;32(2 Suppl):101S.

Wood 1998 {published data only}

Wood MM, Malet PF, Jones A, Prebis M, Harford W, Lee WM. High dose interferon alfa‐2b (IFN) with or without ribavirin (RIB) for chronic hepatitis C in non‐responders to standard therapy (abstract). Hepatology 1998;28(4 Suppl):283S.

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Referencias de otras versiones publicadas de esta revisión

Brok 2003

Brok J, Kjaergard LL, Gluud C. Interferon alpha plus ribavirin versus interferon alpha for chronic hepatitis C ‐ an updated systematic Cochrane review. Journal of Hepatology 2003;23 Suppl(2):129S.

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Jump to:

Bodenheimer 1997

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus antibody and RNA positive.
Elevated transaminases for more than six months.
Histologic evidence of chronic hepatitis.

Exclusion criteria:
Hepatitis B.
Human immune deficiency virus.
Gilberts syndrome.
Chronic or haemolytic anaemia.
Excessive alcohol consume.
Significant concurrent systemic illness.
Haemoglobin less than 10.5 mg/dl.
Hematocrit less than 32%. Immunosuppressive therapy within 6 months before study entry.

Characteristics of included patients:
Mean age: 45 years.
Males: 70%.
Cirrhotics: 17%.
Genotype 1: 89%.
‐ 19% were treatment naive.

Interventions

Ribavirin 1200 mg daily for 36 weeks versus placebo.

Outcomes

Outcomes assessed 16 weeks after the end of treatment.

Notes

The trial included naive, relapsers, and non‐responders.
Quality of life was assessed by self‐developed symptom questionnaires.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not described.

Allocation concealment?

Low risk

"Allocation concealed at independent pharmacy."

Blinding?
All outcomes

Low risk

Patients were randomised "in equal numbers to receive 200 mg ribavirin capsules or three identically appearing placebo capsules twice daily. The placebo was composed of capsules whose primary ingredients were lactose and cellulose."

Incomplete outcome data addressed?
All outcomes

Unclear risk

Report that "two patients refused follow‐up biopsy."

Free of selective reporting?

Unclear risk

Protocol is not available. The authors reported virological response at end of treatment only, but they reported on clinical outcomes and adverse reactions.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Low risk

There was no baseline imbalance in important characteristics.

Free of source of funding bias?

High risk

Grant from Valeant Pharmaceuticals International.

Buti 1991

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Chronic non‐A and non‐B hepatitis.

Exclusion criteria:
Not reported.

Characteristics of included patients:
Mean age and proportion of males, cirrhotics and genotypes not reported.

Interventions

Ribavirin 1200 mg daily for eight weeks versus placebo.

Outcomes

Outcomes assessed at end of treatment.

Notes

Previous antiviral treatment unclear.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not described.

Allocation concealment?

Unclear risk

Not described.

Blinding?
All outcomes

Low risk

placebo‐controlled trial.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Not described.

Free of selective reporting?

Unclear risk

Protocol is not available. The authors reported in the abstract only end of treatment biochemical response.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Unclear risk

Not described.

Free of source of funding bias?

Unclear risk

Not described.

Chemello 1995

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus antibody and RNA positive.
Elevated transaminases for more than six months.
Histologic evidence of chronic hepatitis.

Exclusion criteria:
Cirrhosis.
Other potential cause of liver disease.

Characteristics of included patients:
Mean age: 41 years.
Males: 100%.
Cirrhotics: 0%.
Genotype 1: 40%.

Interventions

Ribavirin 15 mg/kg daily versus interferon 3 million units thrice a week for 26 weeks.

Outcomes

Outcomes assessed 52 weeks after end of treatment.

Notes

This trial also includes a treatment group receiving ribavirin plus interferon.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

"Table of random numbers."

Allocation concealment?

Low risk

"Allocation concealed by sealed envelopes."

Blinding?
All outcomes

High risk

No blinding.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Not described.

Free of selective reporting?

Unclear risk

Protocol is not available. Reported on the primary outcomes in the review.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Low risk

No relevant significant difference.

Free of source of funding bias?

Unclear risk

Not described.

Di Bisceglie 1995b

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus antibody and RNA positive.
Elevated transaminases.
Histologic evidence of chronic hepatitis.

Exclusion criteria:
Therapy with other agents within six months.
Decompensated liver diseases.
Pregnancy.
Anaemia.
Hepatitis B or D.
Human immune deficiency virus.
Alcohol abuse.

Characteristics of included patients:
Mean age: 44 years.
Men: 67%.
Cirrhosis: not described.
Genotype 1: 78%.
71% were treatment naive.

Interventions

Ribavirin 1200 mg daily for 12 months versus placebo.

Outcomes

Outcomes assessed 26 weeks after end of treatment.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Table of random numbers.

Allocation concealment?

Unclear risk

Not described.

Blinding?
All outcomes

Low risk

Use of placebo identical in appearance and given in the same manner as ribavirin.

Incomplete outcome data addressed?
All outcomes

Low risk

"All patients were followed for the full 48 weeks and all had liver biopsy."

Free of selective reporting?

Unclear risk

Protocol is not available. Reported on the primary outcomes in the review.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Low risk

No significant difference.

Free of source of funding bias?

High risk

Support from Valeant Pharmaceuticals International.

Dusheiko 1996

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus antibody and RNA positive.
Elevated transaminases.
Histological evidence of chronic hepatitis.

Exclusion criteria:
No interferon or immunosuppressive therapy within six months.
Alcohol abuse.
Hepatitis B.
Human immune deficiency virus.
Intravenous drug abuse.
Haemoglobin less than 10 g/dl.
Haemolytic anaemia.
Gout or other significant systemic illness.
Other forms of liver disease.
Autoantibodies.

Characteristics of included patients:
Mean age: 44 years.
Males: 86%.
Cirrhotics: not reported.
Genotype 1: 55%.

Interventions

Ribavirin 1000 to 1200 mg daily versus placebo for 24 weeks.

Outcomes

Outcomes assessed 24 weeks after end of treatment.

Notes

The trial included naive, relapsers, and non‐responders.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Table of random numbers.

Allocation concealment?

Low risk

Allocation concealed by sealed envelopes.

Blinding?
All outcomes

Low risk

"Use identical placebo capsules."

Incomplete outcome data addressed?
All outcomes

Low risk

Analysed with intention to treat: "93 had HCV‐RNA measured and 77 had liver biopsy at end of follow‐up."

Free of selective reporting?

Unclear risk

Protocol is not available. The authors reported on the primary outcomes in the review.

Early stopping?

Low risk

Sample size estimation of 120 patients; 118 patients were randomised.

Baseline characteristics

Low risk

No significant difference.

Free of source of funding bias?

High risk

Grant from Valeant Pharmaceuticals International.

Felipe 2000

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus antibody and RNA positive.
Elevated transaminases for at least six months.
Liver biopsy proven chronic hepatitis.
Treatment naive.

Exclusion criteria:
Hepatitis B antigen or anti‐HCV positive. Pregnancy. Decompensated cirrhosis. Hepatocellular carcinoma or other significant concurrent diseases.

Characteristics of included patients:
Mean age: 45 years.
Males: 82%.
Cirrhotics: not reported.
Genotype 1: not reported.

Interventions

Ribavirin 600 mg daily for 8 weeks, then 1000 mg daily for 8 weeks, then 1200 mg daily for 8 weeks versus placebo.

Outcomes

Outcomes assessed 12 weeks after end of treatment.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not described.

Allocation concealment?

Unclear risk

Not described.

Blinding?
All outcomes

Low risk

Use of placebo.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Not described.

Free of selective reporting?

Unclear risk

Protocol is not available. The authors reported only on the end of treatment virological response.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Low risk

No significant difference.

Free of source of funding bias?

High risk

Support from ICI‐Frama Ind. Farmac. Ltda. Grants from CNPq and FAPESP

Gonzalez‐Peralt 1997

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus antibody and RNA positive.
Elevated transaminases for at least six months.
Liver biopsy proven chronic hepatitis.

Exclusion criteria:
Hepatitis B or human immune deficiency virus.

Characteristics of included patients:
Median age: 42 years.
Males: 64%.
Cirrhotics: not reported.
Genotype 1: 86%.

Interventions

Ribavirin 1200 mg daily versus placebo for 36 weeks.

Outcomes

Outcomes assessed 24 weeks after end of treatment.

Notes

Previous antiviral treatment unclear.

A comparison group with 15 patients were receiving interferon, but they were not randomised.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not described.

Allocation concealment?

Unclear risk

Not described.

Blinding?
All outcomes

Low risk

Placebo‐controlled trial.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Not described.

Free of selective reporting?

Unclear risk

Protocol is not available. The authors reported only on the end of treatment virological response.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Low risk

No significant difference.

Free of source of funding bias?

Low risk

Grant from Children's Miracle Network Reasearch Fund.

Hoofnagle 2003

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus RNA positive.
Elevated amino transferase.
Liver biopsy proven chronic hepatitis.
Non‐responders after 24 weeks combination therapy with ribavirin and interferon.

Exclusion criteria:
Symptomatic coronary or cerebrovascular diseases.
Autoimmune diseases.
Renal insufficiency.
Haemolysis or anaemia.
Age younger than 18 years.
Hepatitis B or human immune deficiency virus.

Characteristics of included patients:
Median age: 47 years.
Males: 74%.
Cirrhotics: 15%.
Genotype 1: 97%.

Interventions

Ribavirin 1000 to 1200 mg daily versus placebo for 48 weeks.

Outcomes

Outcomes assessed 24 weeks after end of treatment.

Notes

All patients were treated with interferon plus ribavirin for 24 weeks. Those who did not clear hepatitis C virus were subsequently randomised to ribavirin versus placebo.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not described.

Allocation concealment?

Unclear risk

Not described.

Blinding?
All outcomes

Low risk

"Identical appearing placebo tablets."

Incomplete outcome data addressed?
All outcomes

Low risk

"All had HCV‐RNA measured and all but two had liver biopsy."

Free of selective reporting?

Unclear risk

Protocol is not available. The authors reported on adverse events and clinical outcomes but not on sustained virological response.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Low risk

No significant difference.

Free of source of funding bias?

High risk

Support from Schering‐Ploigh research Institute (placebo tablets).

Kakumu 1993b

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus antibody and RNA positive.
Liver biopsy proven chronic hepatitis.

Exclusion criteria:
Hepatitis B.

Characteristics of included patients:
Median age: 50 years.
Males: 69%.
Cirrhotics: not reported.
Genotype 1: not reported.

Interventions

Ribavirin 800 to 1000 mg daily versus no intervention versus interferon beta 3 million units thrice a week for 24 weeks versus no intervention.

Outcomes

Outcomes assessed 24 weeks after end of treatment.

Notes

Previous antiviral treatment unclear.
This trial also includes a treatment group receiving ribavirin plus interferon.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not described.

Allocation concealment?

Unclear risk

Not described

Blinding?
All outcomes

High risk

No blinding.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Not described.

Free of selective reporting?

Unclear risk

Protocol is not available. The authors reported on the primary outcomes in the review.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Low risk

No significant difference.

Free of source of funding bias?

Unclear risk

Not described.

Khakoo 1998

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus RNA positive.
Histologic evidence of chronic hepatitis.
Treatment naive or relapsers to previous interferon therapy.

Exclusion criteria:
Hepatitis B.
Human immune deficiency virus.
Interferon neutralising antibodies.
Significant other medical or psychiatric illness.
Substance abuse.
Other causes of liver disease or advanced liver disease.

Characteristics of included patients:
Mean age: 38 years.
Males: 63%.
Cirrhotics: not reported.
Genotypes: not reported.

Interventions

Ribavirin 1200 mg daily versus interferon alfa‐2b 3 million units thrice weekly with or without ribavirin 1200 mg daily for six weeks

Outcomes

Outcomes assessed four weeks after end of treatment.

Notes

Patients who completed the full 10 weeks were offered ribavirin plus interferon for 24 weeks.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Sequence generation by computer.

Allocation concealment?

Low risk

Allocation concealed by sealed envelopes.

Blinding?
All outcomes

High risk

No blinding.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Not described.

Free of selective reporting?

Unclear risk

Protocol is not available. The authors did not report on virological response.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Unclear risk

Not described.

Free of source of funding bias?

Unclear risk

Not described.

Pawlotsky 2004

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus 1b RNA positive.
treatment naive.

Exclusion criteria:
Not reported.

Characteristics of included patients:
Mean age: 46 years.
Males: 67%.
Cirrhotics: not reported.
Genotypes. All were genotype 1b.

Interventions

Ribavirin 1000 to 1200 mg daily versus interferon alfa‐2b 3 million units daily versus interferon 3 million units thrice weekly versus no intervention for 12 weeks.

Outcomes

Outcomes assessed at end of treatment.

Notes

This study also includes a treatment group receiving ribavirin plus interferon.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not described.

Allocation concealment?

Unclear risk

Not described

Blinding?
All outcomes

High risk

No blinding.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Not described.

Free of selective reporting?

Unclear risk

Protocol is not available. DId not report on sustained virological response.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Unclear risk

Not described.

Free of source of funding bias?

Unclear risk

Not described.

Sostegni 1998

Methods

Study design: randomised clinical trial.

Participants

‐ Non‐responders to previous interferon treatment.
‐ Mean age 48 years.
‐ Men 82%.
‐ Cirrhosis 22%.
‐ Genotype 1: 68%.
‐ HCV‐RNA limit 50 copies/ml.

Interventions

Leukocyte interferon 3 million units thrice a week or ribavirin 1000 mg daily for 26 weeks.

Outcomes

Outcomes assessed at the end of treatment.

Notes

The trial also includes a third group receiving ribavirin plus interferon. Furthermore, the ribavirin group received interferon after ribavirin. Thus, only data at end of ribavirin treatment are included.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Use of computer.

Allocation concealment?

Unclear risk

Not described.

Blinding?
All outcomes

High risk

No double blinding.

Incomplete outcome data addressed?
All outcomes

Low risk

Report on patients dropping out from study.

Free of selective reporting?

Unclear risk

Protocol is not available.

Early stopping?

Unclear risk

Not described.

Baseline characteristics

Low risk

No significant difference.

Free of source of funding bias?

Unclear risk

Not described.

Stanimirovic 2002

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus antibody and RNA positive.
Elevated aminotransferase for at least six months.
Liver biopsy proven chronic hepatitis.
Treatment naive.

Exclusion criteria:
Pregnancy.
Hepatitis B.
Human immune deficiency virus.
Ascites, hepatic encephalopathy or oesophageal varices.
Significant systemic illness.
Excessive alcohol intake.
Gilbert diseases.
Renal impairment.
Evidence of other forms of liver disease.

Characteristics of included patients:
Mean age: 41 years.
Males: 64%.
Cirrhotics: 8%
Genotypes not reported.

Interventions

Ribavirin 1200 mg daily for 48 weeks or placebo.

Outcomes

Outcomes assessed 16 weeks after end of treatment.

Notes

Treatment naive.
Sustained virological and biochemical response were assessed 16 weeks after the end of treatment.
A decrease in ALT of more than 50% were considered as normalisation.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not described.

Allocation concealment?

Low risk

Allocation concealed at independent medical department.

Blinding?
All outcomes

Low risk

Use of placebo. Furthermore, monitor and nursing staff were blinded.

Incomplete outcome data addressed?
All outcomes

Low risk

Number and reasons for drop‐outs clearly described in 'Final report' page 38 to 40.

Free of selective reporting?

Low risk

Protocol available and reported on relevant and pre‐specified outcomes.

Early stopping?

Low risk

Sample size estimation fulfilled.

Baseline characteristics

Low risk

No significant difference.

Free of source of funding bias?

High risk

Grant from Valeant Pharmaceuticals International.

Veldt 2003

Methods

Study design: randomised clinical trial.

Participants

Inclusion criteria:
Hepatitis C virus antibody and RNA positive.
Elevated aminotransferase.
Liver biopsy proven chronic hepatitis.
Non‐responders to previous antiviral therapy.

Exclusion criteria:
Pregnancy.
Infection with other types of hepatitis.
Metabolic liver diseases.
Liver diseases related to other factors.
Significant medical illness.
Treatment with steroids.
Low levels of haemoglobin, platelet count, or white blood cells.
Hepatocellular carcinoma.
Drug or alcohol addiction.

Characteristics of included patients:
Mean age: 47 years.
Males: 77%.
Cirrhotics: 35%.
Genotype 1: 65%.

Interventions

Ribavirin 1000 to 1200 mg daily versus ribavirin placebo versus interferon 3 million units thrice weekly for 24 weeks.

Outcomes

Outcomes assessed 24 weeks after end of treatment.

Notes

This trial also includes a treatment group receiving ribavirin plus interferon.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not described.

Allocation concealment?

Low risk

Allocation concealment: sealed envelopes.

Blinding?
All outcomes

Low risk

"Use of matched placebo".

Incomplete outcome data addressed?
All outcomes

Low risk

Number and reasons for drop‐outs described (Figure 1).

Free of selective reporting?

Unclear risk

Protocol is not available. The authors reported on the primary outcomes in the review.

Early stopping?

Low risk

Sample size estimation fulfilled.

Baseline characteristics

Low risk

No significant difference.

Free of source of funding bias?

High risk

Financial support form Valeant Pharmaceuticals International and Schering Plough.

Characteristics of excluded studies [ordered by study ID]

Jump to:

Study

Reason for exclusion

Abergel 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Adinolfi 2000

Randomised trial comparing different ribavirin plus interferon regimens.

Andreone 1999a

Randomised trial comparing ribavirin plus interferon versus interferon.

Andreone 1999b

Randomised trial comparing ribavirin plus interferon versus interferon.

Andreone 2000

Randomised trial comparing different ribavirin plus interferon regimens.

Antignano 1999

Randomised trial comparing different ribavirin plus interferon regimens.

Ascione 1998

Randomised trial comparing ribavirin plus interferon versus interferon.

Bacon 1998

Randomised trial comparing different ribavirin plus interferon regimens.

Bailey 1997

Observational study.

Baracetti 2000

Randomised trial comparing different ribavirin plus interferon regimens.

Barbaro 1998a

Randomised trial comparing ribavirin plus interferon versus interferon.

Barbaro 1998b

Randomised trial comparing ribavirin plus interferon versus interferon.

Barbaro 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Barbaro 2000a

Randomised trial comparing ribavirin plus interferon versus interferon.

Bekkering 2000

Observational study.

Bell 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Belli 2001

Randomised trial including patients who had undergone liver transplantation

Bellobouno 1997

Randomised trial comparing ribavirin plus interferon versus interferon.

Bellobouno 1998

Randomised trial comparing different ribavirin plus interferon regimens.

Bellobouno 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Bellobuono 1995

Observational study.

Bellobuono 2000a

Randomised trial comparing ribavirin plus interferon versus interferon.

Bellobuono 2000b

Observational study.

Bellobuono 2000c

Observational study.

Benetti 2001

Randomised trial comparing ribavirin plus interferon versus interferon.

Benhamou 2007

Randomised trial comparing ribavirin vs viramidine.

Berg 2000a

Randomised trial comparing ribavirin plus interferon versus interferon.

Berg 2000b

Randomised trial comparing ribavirin plus interferon versus interferon.

Bernatik 2000

Observational study.

Bernstein 1998

Randomised trial comparing different ribavirin plus interferon regimens.

Bjøro 2000

Randomised trial comparing different ribavirin plus interferon regimens.

Bresci 2000

Randomised trial comparing ribavirin plus interferon versus interferon.

Brillanti 1995

Randomised trial comparing ribavirin plus interferon versus interferon.

Brillanti 1999

Randomised trial comparing ribavirin plus interferon with ribavirin plus interferon plus amantadine.

Brouwer 2001

Randomised trial comparing ribavirin plus interferon versus interferon.

Bugliescu 2000

Randomised trial comparing ribavirin plus interferon versus interferon.

Calanca 2007

Randomised trial comparing ribavirin versus amantadine versus historical control group without antiviral treatment.

Camps 1993

Observational study.

Caremani 1996

Randomised trial comparing ribavirin plus interferon versus interferon.

Cattral 1999

Observational study.

Cavaletto 2000

Randomised trial comparing ribavirin plus interferon versus interferon.

Chapman 2001

Randomised trial comparing ribavirin plus interferon versus interferon.

Cheinquer 1998

Observational study.

Colantoni 2000

Observational study.

Davis 1998

Randomised trial comparing ribavirin plus interferon versus interferon.

De Bac 1998

Possibly randomised trial comparing different ribavirin plus interferon regimens.

De Franceschi 2000

Observational study.

Dettmer 2002

Randomised trial comparing ribavirin plus interferon versus interferon.

Di Bisceglie 1992

Observational study.

Di Bisceglie 1995

Randomised trial comparing ribavirin plus interferon versus interferon.

Di Marco 2000

Randomised trial comparing different ribavirin plus interferon regimens.

Ehardt 2000

Observational study.

el‐Zayadi 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Ersöz 2000

Observational study.

Feher 2000

Observational study.

Ferenci 2000

Randomised trial comparing different ribavirin plus interferon regimens.

Ferenci 2001

Randomised trial comparing ribavirin plus interferon versus interferon.

Fraquelli 2000

Observational study.

Gallego 2000

Randomised trial comparing different ribavirin plus interferon regimens.

Gane 1998

Randomised trial concerning recurrent HCV infection in liver transplant recipients.

Garnier 1997

Observational study.

Gerotto 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Gish 1998

Randomised trial comparing different ribavirin plus interferon regimens.

Gish 2007

Randomised trial comparing ribavirin vs viramidine.

Glue 2000

Randomised trial comparing ribavirin plus interferon versus interferon.

Gross 1999a

Randomised trial comparing ribavirin plus interferon versus interferon.

Gross 1999b

Randomised trial comparing ribavirin plus interferon versus interferon.

Götz 1998

Observational study.

Harris 2000

Observational study.

Herrine 1998

Randomised trial comparing different ribavirin plus interferon regimens.

Junqing 1996

Observational study.

Juszezyk 2000

Observational study.

Kallinowski 1999

Randomised trial comparing different ribavirin plus interferon regimens.

Katsarou 2000

Observational study.

Koshy 2000

Randomised trial comparing ribavirin plus interferon versus interferon.

Lai 1996

Randomised trial comparing ribavirin plus interferon versus interferon.

Lee 1998

Observational study.

Lin 2004

Randomised trial comparing ribavirin vs viramidine.

Lédinghen 2002a

Randomised trial comparing ribavirin plus interferon versus interferon.

Lédinghen 2002b

Randomised trial comparing ribavirin plus interferon versus interferon.

Malik 2002

Randomised trial comparing ribavirin plus interferon versus interferon.

Mangia 2001

Randomised trial comparing ribavirin plus interferon versus interferon.

Marcellin 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Marco 2000

Randomised trial comparing different ribavirin plus interferon regimens.

Marco 2002

Randomised trial comparing ribavirin plus interferon versus interferon.

Mazzaferro 1997

Observational study.

McHutchison 1998

Randomised trial comparing ribavirin plus interferon versus interferon.

Menzel 2000

Randomised trial comparing different regimens of interferon plus amantadine plus ribavirin.

Milella 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Nagayama 2005

Randomised patients that responded (cleared HCV‐RNA) to combination therapy to ribavirin versus placebo.

Nunes 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Perasso 1999

Observational study.

Pol 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Pol 2000a

Randomised trial comparing ribavirin plus interferon versus interferon.

Poordad 2008

Randomised trial comparing ribavirin vs viramidine.

Portal 2000

Randomised trial comparing ribavirin plus interferon versus interferon.

Poynard 1998a

Randomised trial comparing ribavirin plus interferon versus interferon.

Quadri 2000

Observational study.

Reichard 1998

Randomised trial comparing ribavirin plus interferon versus interferon.

Ricchiuti 1996

Randomised trial comparing ribavirin plus interferon versus interferon.

Ricchiuti 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Rosen 1999

Randomised trial comparing different ribavirin plus interferon regimens.

Rothstein 1998

Randomised trial comparing different ribavirin plus interferon regimens.

Salmeron 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Sarin 1999

Randomised trial comparing ribavirin plus interferon versus interferon.

Scotto 1996

Randomised trial comparing ribavirin plus interferon versus interferon.

Shakil 1999

Randomised trial in liver transplant recipients.

Sherif 1996

Observational study.

Shiffman 2000

Randomised trial comparing ribavirin plus interferon versus interferon.

Shiffman 2001

Randomised patients that responded (cleared HCV‐RNA) to combination therapy to ribavirin versus placebo.

Stalke 2000

Observational study.

Tassopoulos 1999

Randomised trial comparing different ribavirin plus interferon regimens.

Teuber 2000

Observational study.

Toccaceli 1997

Randomised trial comparing ribavirin plus interferon versus interferon.

Tripi 1998

Randomised trial comparing ribavirin plus interferon versus ribavirin.

Verbaan 2002

Randomised trial comparing ribavirin plus interferon versus interferon.

Vogel 2002

Randomised trial comparing ribavirin plus interferon versus interferon.

Wiese 2000a

Observational study.

Wood 1998

Randomised trial comparing ribavirin plus interferon versus interferon.

Data and analyses

Open in table viewer
Comparison 1. Ribavirin versus placebo or no intervention

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA) Show forest plot

10

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.1

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA).

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA).

1.1 Sustained virological response

5

353

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.02, 0.03]

1.2 End of treatment virological response

10

513

Risk Difference (M‐H, Fixed, 95% CI)

‐ [‐0.03, 0.03]

2 Liver‐related morbidity and all‐cause mortality Show forest plot

11

521

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.02, 0.03]

Analysis 1.2

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 2 Liver‐related morbidity and all‐cause mortality.

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 2 Liver‐related morbidity and all‐cause mortality.

3 Adverse events Show forest plot

7

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.3

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 3 Adverse events.

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 3 Adverse events.

3.1 Depression

1

59

Risk Difference (M‐H, Fixed, 95% CI)

0.17 [0.01, 0.33]

3.2 Anaemia

7

444

Risk Difference (M‐H, Fixed, 95% CI)

0.16 [0.11, 0.22]

3.3 Fatique (weakness)

3

172

Risk Difference (M‐H, Fixed, 95% CI)

0.05 [‐0.01, 0.11]

3.4 Irritability

2

138

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [‐0.03, 0.08]

3.5 Anxiety

1

58

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [‐0.06, 0.12]

3.6 Pruritus (itching)

3

172

Risk Difference (M‐H, Fixed, 95% CI)

0.06 [‐0.00, 0.12]

3.7 Infections

1

58

Risk Difference (M‐H, Fixed, 95% CI)

0.17 [0.03, 0.32]

3.8 Cough

1

59

Risk Difference (M‐H, Fixed, 95% CI)

0.21 [0.04, 0.38]

3.9 Chest pain

2

139

Risk Difference (M‐H, Fixed, 95% CI)

0.07 [0.00, 0.14]

3.10 Skin disorders (non‐specific)

1

116

Risk Difference (M‐H, Fixed, 95% CI)

0.14 [0.06, 0.23]

3.11 Nervous system disorders (Non‐specific)

1

116

Risk Difference (M‐H, Fixed, 95% CI)

0.14 [0.06, 0.23]

3.12 Gastrointestinal pain

1

80

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [‐0.04, 0.09]

3.13 Headache

1

80

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [‐0.04, 0.09]

3.14 Vasculitis

1

79

Risk Difference (M‐H, Fixed, 95% CI)

0.02 [‐0.04, 0.09]

3.15 Dose reductions

6

387

Risk Difference (M‐H, Fixed, 95% CI)

0.11 [0.06, 0.16]

3.16 Treatment discontinuations

6

428

Risk Difference (M‐H, Fixed, 95% CI)

0.05 [0.01, 0.10]

4 Failure of biochemical response (number of patients with elevated transaminase) Show forest plot

10

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.4

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 4 Failure of biochemical response (number of patients with elevated transaminase).

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 4 Failure of biochemical response (number of patients with elevated transaminase).

4.1 Sustained biochemical response

5

294

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.05, 0.06]

4.2 End of treatment biochemical response

10

509

Risk Difference (M‐H, Fixed, 95% CI)

‐0.23 [‐0.29, ‐0.17]

5 Failure of histologic response (number of patients without improvement in liver histology) Show forest plot

3

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.5

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 5 Failure of histologic response (number of patients without improvement in liver histology).

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 5 Failure of histologic response (number of patients without improvement in liver histology).

5.1 Combined necro‐inflammatory and fibrosis score (Intention to treat)

3

211

Risk Difference (M‐H, Fixed, 95% CI)

‐0.14 [‐0.25, ‐0.02]

5.2 Combined necro‐inflammatory and fibrosis score (Per protocol)

3

156

Risk Difference (M‐H, Fixed, 95% CI)

‐0.20 [‐0.35, ‐0.06]

6 Quality of life Show forest plot

1

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.6

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 6 Quality of life.

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 6 Quality of life.

6.1 Improvement of fatigue at end of treatment

1

59

Risk Difference (M‐H, Fixed, 95% CI)

‐0.11 [‐0.27, 0.06]

Open in table viewer
Comparison 2. Ribavirin versus interferon

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA) Show forest plot

5

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.1

Comparison 2 Ribavirin versus interferon, Outcome 1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA).

Comparison 2 Ribavirin versus interferon, Outcome 1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA).

1.1 Sustained virological response

2

48

Risk Difference (M‐H, Fixed, 95% CI)

0.13 [‐0.04, 0.29]

1.2 End of treatment virological response

5

151

Risk Difference (M‐H, Fixed, 95% CI)

0.17 [0.07, 0.27]

2 Liver‐related and all‐cause morbidity and mortality Show forest plot

5

151

Risk Difference (M‐H, Fixed, 95% CI)

0.0 [‐0.06, 0.06]

Analysis 2.2

Comparison 2 Ribavirin versus interferon, Outcome 2 Liver‐related and all‐cause morbidity and mortality.

Comparison 2 Ribavirin versus interferon, Outcome 2 Liver‐related and all‐cause morbidity and mortality.

3 Failure of biochemical response (number of patients with elevated alanine aminotransferase) Show forest plot

4

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.3

Comparison 2 Ribavirin versus interferon, Outcome 3 Failure of biochemical response (number of patients with elevated alanine aminotransferase).

Comparison 2 Ribavirin versus interferon, Outcome 3 Failure of biochemical response (number of patients with elevated alanine aminotransferase).

3.1 Sustained biochemical response

2

48

Risk Difference (M‐H, Fixed, 95% CI)

0.17 [‐0.01, 0.35]

3.2 End of treatment biochemical response

4

135

Risk Difference (M‐H, Fixed, 95% CI)

0.17 [0.05, 0.29]

4 Adverse events Show forest plot

4

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.4

Comparison 2 Ribavirin versus interferon, Outcome 4 Adverse events.

Comparison 2 Ribavirin versus interferon, Outcome 4 Adverse events.

4.1 Flu‐like syndrome (non‐specific)

1

30

Risk Difference (M‐H, Fixed, 95% CI)

‐0.2 [‐0.42, 0.02]

4.2 Weight loss

1

30

Risk Difference (M‐H, Fixed, 95% CI)

0.0 [‐0.18, 0.18]

4.3 Fatique/Weakness

2

54

Risk Difference (M‐H, Fixed, 95% CI)

0.11 [‐0.09, 0.31]

4.4 Irritability

2

93

Risk Difference (M‐H, Fixed, 95% CI)

‐0.00 [‐0.12, 0.11]

4.5 Abdominal pain

2

93

Risk Difference (M‐H, Fixed, 95% CI)

0.13 [0.03, 0.23]

4.6 Diarrhea

1

30

Risk Difference (M‐H, Fixed, 95% CI)

0.13 [‐0.06, 0.33]

4.7 Pruritus

2

93

Risk Difference (M‐H, Fixed, 95% CI)

0.06 [‐0.03, 0.15]

4.8 Herpes labialis

1

30

Risk Difference (M‐H, Fixed, 95% CI)

0.13 [‐0.11, 0.37]

4.9 Anaemia

2

93

Risk Difference (M‐H, Fixed, 95% CI)

0.09 [‐0.01, 0.18]

4.10 Headache

1

24

Risk Difference (M‐H, Fixed, 95% CI)

‐0.17 [‐0.51, 0.17]

4.11 Pharyngitis

1

24

Risk Difference (M‐H, Fixed, 95% CI)

0.08 [‐0.12, 0.29]

4.12 Viral infections

1

24

Risk Difference (M‐H, Fixed, 95% CI)

0.08 [‐0.12, 0.29]

4.13 Myalgia

1

24

Risk Difference (M‐H, Fixed, 95% CI)

‐0.08 [‐0.29, 0.12]

4.14 Dose reductions

3

72

Risk Difference (M‐H, Fixed, 95% CI)

0.08 [‐0.04, 0.21]

4.15 Treatment discontinuations

3

117

Risk Difference (M‐H, Fixed, 95% CI)

0.01 [‐0.09, 0.11]

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included trials.
Figures and Tables -
Figure 1

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included trials.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Figures and Tables -
Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Trial sequential analysis illustrating that the cumulative Z‐curve (blue) has not crossed the monitoring boundary (red) but have surpassed the information size (n = 232) needed to detect of reject an effect size corresponding to a number needed to treat of 10 patient (or fewer) for ribavirin. Thus we can rule out a number needed to treat of 10 patients (or fewer) for ribavirin regarding sustained virological response.Trial sequential analysis was performed with a type I error of 5% and type II error of 20% (80% power). We assumed a baseline event rate of 97% without sustained virological response in the placebo/no intervention group. We used an event rate of 87% (number needed to treat = 10 patients) without sustained virological response in the ribavirin group.
Figures and Tables -
Figure 3

Trial sequential analysis illustrating that the cumulative Z‐curve (blue) has not crossed the monitoring boundary (red) but have surpassed the information size (n = 232) needed to detect of reject an effect size corresponding to a number needed to treat of 10 patient (or fewer) for ribavirin. Thus we can rule out a number needed to treat of 10 patients (or fewer) for ribavirin regarding sustained virological response.

Trial sequential analysis was performed with a type I error of 5% and type II error of 20% (80% power). We assumed a baseline event rate of 97% without sustained virological response in the placebo/no intervention group. We used an event rate of 87% (number needed to treat = 10 patients) without sustained virological response in the ribavirin group.

Trial sequential analysis illustrating that the cumulative Z‐curve (blue) has not crossed the monitoring boundary (red) nor reached the information size (n = 3014) needed to detect of reject an effect size corresponding to a number needed to treat of 50 (or fewer) for ribavirin. Thus we can not rule out a number needed to treat of 50 (or fewer) for ribavirin regarding sustained virological response. Additionally 2661 (3014 ‐ 353) patients are needed to detect or reject this effect size.Trial sequential analysis was performed with a type I error of 5% and type II error of 20% (80% power). We assumed a baseline event rate of 97% for sustained virological response in the placebo/no intervention group. We used an event rate of 95% (number needed to treat = 50) without sustained virological response in the ribavirin group.
Figures and Tables -
Figure 4

Trial sequential analysis illustrating that the cumulative Z‐curve (blue) has not crossed the monitoring boundary (red) nor reached the information size (n = 3014) needed to detect of reject an effect size corresponding to a number needed to treat of 50 (or fewer) for ribavirin. Thus we can not rule out a number needed to treat of 50 (or fewer) for ribavirin regarding sustained virological response. Additionally 2661 (3014 ‐ 353) patients are needed to detect or reject this effect size.

Trial sequential analysis was performed with a type I error of 5% and type II error of 20% (80% power). We assumed a baseline event rate of 97% for sustained virological response in the placebo/no intervention group. We used an event rate of 95% (number needed to treat = 50) without sustained virological response in the ribavirin group.

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA).
Figures and Tables -
Analysis 1.1

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA).

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 2 Liver‐related morbidity and all‐cause mortality.
Figures and Tables -
Analysis 1.2

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 2 Liver‐related morbidity and all‐cause mortality.

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 3 Adverse events.
Figures and Tables -
Analysis 1.3

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 3 Adverse events.

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 4 Failure of biochemical response (number of patients with elevated transaminase).
Figures and Tables -
Analysis 1.4

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 4 Failure of biochemical response (number of patients with elevated transaminase).

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 5 Failure of histologic response (number of patients without improvement in liver histology).
Figures and Tables -
Analysis 1.5

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 5 Failure of histologic response (number of patients without improvement in liver histology).

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 6 Quality of life.
Figures and Tables -
Analysis 1.6

Comparison 1 Ribavirin versus placebo or no intervention, Outcome 6 Quality of life.

Comparison 2 Ribavirin versus interferon, Outcome 1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA).
Figures and Tables -
Analysis 2.1

Comparison 2 Ribavirin versus interferon, Outcome 1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA).

Comparison 2 Ribavirin versus interferon, Outcome 2 Liver‐related and all‐cause morbidity and mortality.
Figures and Tables -
Analysis 2.2

Comparison 2 Ribavirin versus interferon, Outcome 2 Liver‐related and all‐cause morbidity and mortality.

Comparison 2 Ribavirin versus interferon, Outcome 3 Failure of biochemical response (number of patients with elevated alanine aminotransferase).
Figures and Tables -
Analysis 2.3

Comparison 2 Ribavirin versus interferon, Outcome 3 Failure of biochemical response (number of patients with elevated alanine aminotransferase).

Comparison 2 Ribavirin versus interferon, Outcome 4 Adverse events.
Figures and Tables -
Analysis 2.4

Comparison 2 Ribavirin versus interferon, Outcome 4 Adverse events.

Comparison 1. Ribavirin versus placebo or no intervention

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA) Show forest plot

10

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Sustained virological response

5

353

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.02, 0.03]

1.2 End of treatment virological response

10

513

Risk Difference (M‐H, Fixed, 95% CI)

‐ [‐0.03, 0.03]

2 Liver‐related morbidity and all‐cause mortality Show forest plot

11

521

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.02, 0.03]

3 Adverse events Show forest plot

7

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Depression

1

59

Risk Difference (M‐H, Fixed, 95% CI)

0.17 [0.01, 0.33]

3.2 Anaemia

7

444

Risk Difference (M‐H, Fixed, 95% CI)

0.16 [0.11, 0.22]

3.3 Fatique (weakness)

3

172

Risk Difference (M‐H, Fixed, 95% CI)

0.05 [‐0.01, 0.11]

3.4 Irritability

2

138

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [‐0.03, 0.08]

3.5 Anxiety

1

58

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [‐0.06, 0.12]

3.6 Pruritus (itching)

3

172

Risk Difference (M‐H, Fixed, 95% CI)

0.06 [‐0.00, 0.12]

3.7 Infections

1

58

Risk Difference (M‐H, Fixed, 95% CI)

0.17 [0.03, 0.32]

3.8 Cough

1

59

Risk Difference (M‐H, Fixed, 95% CI)

0.21 [0.04, 0.38]

3.9 Chest pain

2

139

Risk Difference (M‐H, Fixed, 95% CI)

0.07 [0.00, 0.14]

3.10 Skin disorders (non‐specific)

1

116

Risk Difference (M‐H, Fixed, 95% CI)

0.14 [0.06, 0.23]

3.11 Nervous system disorders (Non‐specific)

1

116

Risk Difference (M‐H, Fixed, 95% CI)

0.14 [0.06, 0.23]

3.12 Gastrointestinal pain

1

80

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [‐0.04, 0.09]

3.13 Headache

1

80

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [‐0.04, 0.09]

3.14 Vasculitis

1

79

Risk Difference (M‐H, Fixed, 95% CI)

0.02 [‐0.04, 0.09]

3.15 Dose reductions

6

387

Risk Difference (M‐H, Fixed, 95% CI)

0.11 [0.06, 0.16]

3.16 Treatment discontinuations

6

428

Risk Difference (M‐H, Fixed, 95% CI)

0.05 [0.01, 0.10]

4 Failure of biochemical response (number of patients with elevated transaminase) Show forest plot

10

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Sustained biochemical response

5

294

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.05, 0.06]

4.2 End of treatment biochemical response

10

509

Risk Difference (M‐H, Fixed, 95% CI)

‐0.23 [‐0.29, ‐0.17]

5 Failure of histologic response (number of patients without improvement in liver histology) Show forest plot

3

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Combined necro‐inflammatory and fibrosis score (Intention to treat)

3

211

Risk Difference (M‐H, Fixed, 95% CI)

‐0.14 [‐0.25, ‐0.02]

5.2 Combined necro‐inflammatory and fibrosis score (Per protocol)

3

156

Risk Difference (M‐H, Fixed, 95% CI)

‐0.20 [‐0.35, ‐0.06]

6 Quality of life Show forest plot

1

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Improvement of fatigue at end of treatment

1

59

Risk Difference (M‐H, Fixed, 95% CI)

‐0.11 [‐0.27, 0.06]

Figures and Tables -
Comparison 1. Ribavirin versus placebo or no intervention
Comparison 2. Ribavirin versus interferon

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Failure of serum virological response (number of patients with detectable hepatitis C virus RNA) Show forest plot

5

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Sustained virological response

2

48

Risk Difference (M‐H, Fixed, 95% CI)

0.13 [‐0.04, 0.29]

1.2 End of treatment virological response

5

151

Risk Difference (M‐H, Fixed, 95% CI)

0.17 [0.07, 0.27]

2 Liver‐related and all‐cause morbidity and mortality Show forest plot

5

151

Risk Difference (M‐H, Fixed, 95% CI)

0.0 [‐0.06, 0.06]

3 Failure of biochemical response (number of patients with elevated alanine aminotransferase) Show forest plot

4

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Sustained biochemical response

2

48

Risk Difference (M‐H, Fixed, 95% CI)

0.17 [‐0.01, 0.35]

3.2 End of treatment biochemical response

4

135

Risk Difference (M‐H, Fixed, 95% CI)

0.17 [0.05, 0.29]

4 Adverse events Show forest plot

4

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Flu‐like syndrome (non‐specific)

1

30

Risk Difference (M‐H, Fixed, 95% CI)

‐0.2 [‐0.42, 0.02]

4.2 Weight loss

1

30

Risk Difference (M‐H, Fixed, 95% CI)

0.0 [‐0.18, 0.18]

4.3 Fatique/Weakness

2

54

Risk Difference (M‐H, Fixed, 95% CI)

0.11 [‐0.09, 0.31]

4.4 Irritability

2

93

Risk Difference (M‐H, Fixed, 95% CI)

‐0.00 [‐0.12, 0.11]

4.5 Abdominal pain

2

93

Risk Difference (M‐H, Fixed, 95% CI)

0.13 [0.03, 0.23]

4.6 Diarrhea

1

30

Risk Difference (M‐H, Fixed, 95% CI)

0.13 [‐0.06, 0.33]

4.7 Pruritus

2

93

Risk Difference (M‐H, Fixed, 95% CI)

0.06 [‐0.03, 0.15]

4.8 Herpes labialis

1

30

Risk Difference (M‐H, Fixed, 95% CI)

0.13 [‐0.11, 0.37]

4.9 Anaemia

2

93

Risk Difference (M‐H, Fixed, 95% CI)

0.09 [‐0.01, 0.18]

4.10 Headache

1

24

Risk Difference (M‐H, Fixed, 95% CI)

‐0.17 [‐0.51, 0.17]

4.11 Pharyngitis

1

24

Risk Difference (M‐H, Fixed, 95% CI)

0.08 [‐0.12, 0.29]

4.12 Viral infections

1

24

Risk Difference (M‐H, Fixed, 95% CI)

0.08 [‐0.12, 0.29]

4.13 Myalgia

1

24

Risk Difference (M‐H, Fixed, 95% CI)

‐0.08 [‐0.29, 0.12]

4.14 Dose reductions

3

72

Risk Difference (M‐H, Fixed, 95% CI)

0.08 [‐0.04, 0.21]

4.15 Treatment discontinuations

3

117

Risk Difference (M‐H, Fixed, 95% CI)

0.01 [‐0.09, 0.11]

Figures and Tables -
Comparison 2. Ribavirin versus interferon