Intervention Review

You have free access to this content

Aminoadamantanes for chronic hepatitis C

  1. Mieke H Lamers1,2,*,
  2. Mark Broekman1,
  3. Joost PH Drenth1,
  4. Christian Gluud2

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 3 MAY 2014

Assessed as up-to-date: 30 MAR 2014

DOI: 10.1002/14651858.CD010125.pub2


How to Cite

Lamers MH, Broekman M, Drenth JPH, Gluud C. Aminoadamantanes for chronic hepatitis C. Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD010125. DOI: 10.1002/14651858.CD010125.pub2.

Author Information

  1. 1

    Radboud University Medical Center Nijmegen, Department of Gastroenterology and Hepatology, Nijmegen, Netherlands

  2. 2

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, The Cochrane Hepato-Biliary Group, Copenhagen, Denmark

*Mieke H Lamers, Department of Gastroenterology and Hepatology, Radboud University Medical Center Nijmegen, Geert Grooteplein Zuid 10, Nijmegen, 6525 GA, Netherlands. m.lamers@mdl.umcn.nl.

Publication History

  1. Publication Status: New
  2. Published Online: 3 MAY 2014

SEARCH

References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Adinolfi 2003 {published data only}
  • Adinolfi LE, Marracino M, Tonziello A, Utili R, Andreana A, Giordano M, et al. Interferon induction plus ribavirin and amantadine as a novel approach for treatment of interferon nonresponder chronic hepatitis C patients. Hepatology 2000;32:352A.
  • 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 patiens: a randomized controlled pilot study. Journal of Hepatology 2000;32:107.
  • Adinolfi LE, Utili R, Tonziello A, Ruggiero G. Effects of alpha interferon induction plus ribavirin with or without amantadine in the treatment of interferon non-responsive chronic hepatitis C: a randomised trial. Gut 2003;52(5):701-5. [PUBMED: 12692056]
Angelico 2004 {published data only}
  • Angelico M, Cepparulo M, Angelico F, Barlattani A, Di Candilo F, Della Vecchia R, et al. A randomized controlled trial of amantadine plus interferon alpha-2a vs. interferon alpha-2a in naive patients with chronic hepatitis C randomized based on early response to interferon alpha-2a alone. Hepatology 2002;36(4):589A.
  • Angelico M, Cepparulo M, Angelico F, Francioso S, Barlattani A, Di Candilo F, et al. A randomized controlled trial of amantadine plus interferon-alpha2a vs. interferon-alpha2a alone in naive patients with chronic hepatitis C randomized according to the early virological response to interferon-alpha2a monotherapy. Alimentary Pharmacology & Therapeutics 2004;19(3):339-47. [PUBMED: 14984381]
Angelico 2008 {published data only}
  • Angelico M, Koehler-Horst B, Piccolo P, Angelico F, Gentile S, Francioso S, et al. Final results of the SMIEC trial in naive patients with hepatitis C: double therapy (peginterferon alfa2a + ribavirin) vs peginterferon monotherapy in early viral responders and vs triple therapy (peginterferon + ribavirin + amantadine) in early non responders. Hepatology 2005;42:696A.
  • Angelico M, Koehler-Horst B, Piccolo P, Angelico F, Gentile S, Francioso S, et al. Peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a monotherapy in early virological responders and peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a, ribavirin and amantadine triple therapy in early virological nonresponders: the SMIEC II trial in naive patients with chronic hepatitis C. European Journal of Gastroenterology & Hepatology 2008;20(7):680-7. [PUBMED: 18679072]
Bacosi 2002 {published data only}
  • Bacosi M, Russo F, D'innocenzo S, Santolamazza M, Miglioresi L, Ursitti A, et al. Amantadine and interferon in the combined treatment of hepatitis C virus in elderly patients. Hepatology Research 2002;22(3):231-9. [PUBMED: 11882420]
Baisini 2003 {published data only}
  • Baisini O, Gracielle Pigozzi M, Benini F, Stellini R, Reggiani A, Quattrocchi D, et al. A randomised, open label, controlled trial on the effect of interferon plus amantadine compared with interferon alone for treatment of chronic hepatitis C. Hepatology Research 2003;26(3):167-73. [PUBMED: 12850687]
  • Gracielle Pigozzi M, Stellini R, Reggiani A, Baisini O, Salmi A, Andri G, et al. Interferon (IFN) vs interferon + amantadine hydrochloride (IFN+A) for treatment of chronic hepatitis C: an ongoing multicentre randomized trial. Gastroenterology 2000;118(4):A1480.
  • Lanzini A, Pigozzo MG, Stellini R, Reggiani A, Salmi A, Andri A, et al. Interferon (IFN) vs interferon + amantadine (IFN+A) for treatment of chronic hepatitis C: results of a randomised controlled trial. Hepatology 2001;34(4):338A.
Berg 2003 {published data only}
  • Berg T, Kronenberger B, Hinrichsen H, Gerlach T, Buggisch P, Herrmann E, et al. Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo-controlled trial. Hepatology 2003;37(6):1359-67. [PUBMED: 12774015]
  • Berg T, Kronenberger B, Hinrichsen H, Gerlach T, Buggisch P, Spengler U, et al. Triple therapy with amantadine sulphate plus ribavirin and interferon-alpha in previously untreated patients with chronic hepatitis C: results of a double-blind, placebo-controlled trial. Journal of Hepatology 2002;36:3.
  • Berg T, Kronenberger, B, Hinrichsen H, Gerlach T, Buggisch P, Spengler U, et al. Randomized, double-blind, placebo-controlled trial of high-dose interferon-alfa induction combination therapy with and without amantadine sulphate in previously untreated patients with chronic hepatitis C. Hepatology 2001;34:330A.
  • Kronenberger B, Berg T, Herrmann E, Hinrichsen H, Gerlach T, Buggisch P, et al. Efficacy of amantadine on quality of life in patients with chronic hepatitis C treated with interferon-α and ribavirin: results from a randomized, placebo-controlled, double-blind trial. European Journal of Gastroenterology & Hepatology 2007;19:639-46.
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. [PUBMED: 10363198]
Brillanti 2000 {published data only}
Calay 2005 {published data only}
  • Calay V, Hachemane S, Pageaux GP, Bourliere M, Portal I, Mathurin P, et al. Does amantadine improve the virological sustained response of naive patients with chronic hepatitis C in association with peg-interferon-ribavirin combination? A prospective, randomised, multicenter, double-blind study: preliminary results in 200 patients. Hepatology 2005;44:704A-5A.
  • Calay V, Hachemane S, Pageaux GP, Canva M, Bourliere M, Portal I, et al. A multicentric, randomized, controlled, double-blind study (TRIPEG): PEGINF α-2b, ribavirin and amantadine or PEGINF α-2b, ribavirin and placebo, in 269 naive patients with chronic hepatitis C. Journal of Hepatology 2006;44:S220.
Caronia 2001 {published data only}
  • Caronia S, Bassendine MF, Barry R, Mills P, Naoumov NV, Fox R, et al. Interferon plus amantadine versus interferon alone in the treatment of naive patients with chronic hepatitis C: a UK multicentre study. Journal of Hepatology 2001;35(4):512-6. [PUBMED: 11682036]
  • Caronia S, Bassendine MF, Mills P, Naumov N, Fox R, Lowes R, et al. Interferon plus amantadine versus interferon alone in the treatment of naive patients with chronic hepatitis C: a UK multicentre study. Journal of Hepatology 2000;32:110.
  • Caronia S, Crossey M, Bassendine M, Mills P, Fox R, Naoumov N, et al. Interferon plus amantadine versus interferon alone in the treatment of naive patients with chronic hepatitis C: interim analysis of multicentre study. Hepatology 1999;30:628A.
  • Caronia S, Crossey M, Murray-Lyon I, Lypsnyi D, Main J, Thomas HC, et al. A pilot study of interferon plus amantadine versus interferon alone in the treatment of chronic hepatitis C. Journal of Hepatology 1999;30:138.
Caronia 2001a {published data only}
  • Caronia S, Bassendine MF, Barry R, Mills P, Naoumov NV, Fox R, et al. Interferon plus amantadine versus interferon alone in the treatment of naive patients with chronic hepatitis C: a UK multicentre study. Journal of Hepatology 2001;35(4):512-6. [PUBMED: 11682036]
Ciancio 2006 {published data only}
  • Ciancio A, Picciotto A, Giordanino C, Smedile A, Tabone M, Manca A, et al. A randomised trial of pegylated interferon alpha-2a plus ribavirin with or without amantadine in the re-treatment of patients with chronic hepatitis C not responding to standard interferon and ribavirin. Journal of Clinical Virology 2006;36:S148.
  • Ciancio A, Picciotto A, Giordanino C, Smedile A, Tabone M, Manca A, et al. A randomized trial of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in the re-treatment of patients with chronic hepatitis C not responding to standard interferon and ribavirin. Alimentary Pharmacology & Therapeutics 2006;24(7):1079-86. [PUBMED: 16984502]
Cornberg 2000 {published data only}
  • Cornberg M, Jaeckel M, Schueler A, Koerbel JN, Wedemeyer H, Mansuroglu T, et al. Treatment of chronic hepatitis C in nonresponder patients with high daily induction dosing of interferon-alfa, ribavirin and amantadine/placebo. Hepatology 2000;21:351A.
Ferenci 2006 {published data only}
  • Ferenci P, Formann E, Gschwantler M, Laferl H, Brunner H, Hackl F, et al. Prospective evaluation of the 24 hour interferon (IFN) induced decline in hepatitis C virus genotype 1 load to predict sustained virologic response (SVR) to peginterferon-alfa2a/ribavirin combination therapy with or without amantadine. Journal of Hepatology 2004;40:141.
  • Ferenci P, Formann E, Laferl H, Gschwantler M, Hackl F, Brunner H, et al. Randomized, controlled, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) (Pegasys®) plus ribavirin (Copegus®) and amantadine (AMA) or placebo in patients with chronic hepatitis C genotype 1 infection. Hepatology 2004;40:396A.
  • Ferenci P, Formann E, Laferl H, Gschwantler M, Hackl F, Brunner H, et al. Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) plus ribavirin with or without amantadine in treatment-naive patients with chronic hepatitis C genotype 1 infection. Journal of Hepatology 2006;44(2):275-82. [PUBMED: 16338019]
  • Formann E, Jessner W, Hubmann R, Datz C, Munda-Steindl P, Klingler A, et al. Effect of amantadine on quality of life and fatigue in patients with chronic hepatitis C participating in a prospective, double blind, placebo controlled, randomized trial of treatment with pegylated interferon alfa2a/ribavirin. Hepatology 2004;40:338A.
Gaeta 2001 {published data only}
  • Gaeta GB, Stornaiuolo G, Ascione T, Stanzione M, Pasquazzi C, Cimono L, et al. Interferon alfa-2a (IFN) plus amantadine in chronic hepatitis C resistant to IFN-α alone: a pilot randomised study. Hepatology 1999;30:632A.
  • Gaeta GB, Stornaiuolo G, Stanzione M, Ascione T, Pasquazzi C, Taliani G, et al. Interferon-alpha plus amantadine in chronic hepatitis C resistant to interferon alone: a pilot randomized study. Journal of Viral Hepatitis 2001;8(4):284-6. [PUBMED: 11454180]
Gramenzi 2007 {published data only}
  • Andreone P, Gramenzi A, Cursaro C, Pirraglia C, Verrucchi G, Attard L, et al. IFN plus ribavirin and amantadine for IFN-sensitive patients with chronic hepatitis C: results of a multicenter, randomized, controlled trial. Journal of Hepatology 2003;38(S2):124.
  • Gramenzi A, Andreone P, Cursaro C, Verucchi G, Boccia S, Giacomoni PL, et al. A randomized trial of induction doses of interferon alone or in combination with ribavirin or ribavirin plus amantadine for treatment of nonresponder patients with chronic hepatitis C. Journal of Gastroenterology 2007;42(5):362-7. [PUBMED: 17530360]
Hasan 2004 {published data only}
  • Hasan F, Al-Khaldi J, Asker H, Al-Ajmi M, Owayed S, Varghese R, et al. Peginterferon alpha-2b plus ribavirin with or without amantadine [correction of amantidine] for the treatment of non-responders to standard interferon and ribavirin. Antiviral Therapy 2004;9(4):499-503. [PUBMED: 15456080]
Helbling 2002 {published data only}
  • Helbling B, Hermann R, Stamenic I, Viani F, Gonvers JJ, Dufour JF, et al. Interferon alfa-2a (IFN) and amantadine (A) or placebo (P) in IFN-naive patients with chronic hepatitis C (CHC): a double-blind, randomized, placebo-controlled trial. Hepatology 2001;34(4):331A.
  • Helbling B, Stamenic I, Viani F, Gonvers JJ, Dufour JF, Reichen J, et al. Interferon and amantadine in naive chronic hepatitis C: a double-blind, randomized, placebo-controlled trial. Hepatology 2002;35(2):447-54. [PUBMED: 11826422]
Herrine 2005 {published data only}
  • Herrine SK, Brown RS Jr, Bernstein DE, Ondovik MS, Lentz E, Te H. Peginterferon alpha-2a combination therapies in chronic hepatitis C patients who relapsed after or had a viral breakthrough on therapy with standard interferon alpha-2b plus ribavirin: a pilot study of efficacy and safety. Digestive Diseases and Sciences 2005;50(4):719-26. [PUBMED: 15844708]
Jorge 2001 {published data only}
  • Jorge FA, Tanno H, Igartua EB, Pinchuk L, Sorda JA, Curciarello J, et al. Interferon induction treatment with and without amantadine HCl (AHCl) in patients with chronic hepatitis C. Journal of Hepatology 2001;34:156-7.
Langlet 2009 {published data only}
  • Langlet P, D'Heygere F, Henrion J, Adler M, Delwaide J, Van Vlierberghe H, et al. Clinical trial: a randomized trial of pegylated-interferon-alpha-2a plus ribavirin with or without amantadine in treatment-naive or relapsing chronic hepatitis C patients. Alimentary Pharmacology & Therapeutics 2009;30(4):352-63. [PUBMED: 19485978]
Mangia 2001 {published data only}
  • Mangia A, Minerva N, Annese M, Leandro G, Villani MR, Santoro R, et al. A randomized trial of amantadine and interferon versus interferon alone as initial treatment for chronic hepatitis C. Hepatology 2001;33(4):989-93. [PUBMED: 11283865]
  • Mangia A, Santoro R, Villani MR, Soccio T, Cela O, Annese M, et al. Long term response to amantadine + interferon is significantly higher than that to interferon alone in chronic hepatitis C: final report of a randomized clinical trial. Hepatology 2000;32:318A.
Maynard 2006 {published data only}
  • Maynard M, Ahmed SNS, Bailly F, Rozier F, Benmakhlouf N, Bourne-Branchu V. Retreatment of IFN/ribavirin non-responder hepatitis C patients: benefit of peg-interferon/ribavirin/amantadine. Hepatology 2004;40:398A.
  • Maynard M, Pradat P, Bailly F, Rozier F, Nemoz C, Si Ahmed SN, et al. Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI). Journal of Hepatology 2006;44(3):484-90. [PUBMED: 16426697]
Mendez-Navarro 2010 {published data only}
  • Mendez-Navarro J, Chirino RA, Corey KE, Gorospe EC, Zheng H, Chung R, et al. Assessment and prediction of sustained virological response among treatment-naive Latinos with, genotype 1 HCV treated with standard double versus triple therapy with amantadine. Hepatology 2009;50:707A.
  • Mendez-Navarro J, Chirino RA, Corey KE, Gorospe EC, Zheng H, Moran S, et al. A randomized controlled trial of double versus triple therapy with amantadine for genotype 1 chronic hepatitis C in Latino patients. Digestive Diseases and Sciences 2010;55(9):2629-35. [PUBMED: 19960257]
Pessoa 2012 {published data only}
  • Cheinquer H, Pessoa M, Almeida P, Silva G, Patelli M, Parana R, et al. Prospective randomized study of peginterferon alpha-2a plus ribavirin, in hepatitis C patients non-responders or relapsers to interferon-alpha and ribavirin. Journal of Hepatology 2006;44:S209.
  • Pessoa MG, Cheinquer H, Almeida PR, Silva GF, Lima MP, Parana R, et al. Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin +/- amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial. Annals of Hepatology 2012;11(1):52-61. [PUBMED: 22166561]
Piai 2003 {published data only}
  • Piai G, Rocco P, Tartaglione MT, Ciarleglio A, Focareta R, Grimaldi E, et al. Triple (interferon, ribavirin, amantadine) versus double (interferon, ribavirin) re-therapy for interferon relapser genotype 1b HCV chronic active hepatitis patients. Hepatology Research 2003;25(4):355-63. [PUBMED: 12699845]
Salmeron 2007 {published data only}
  • Salmeron J, Diago M, Andrade R, Perez R, Sola R, Romero M, et al. Induction doses of interferon-alpha-2a in combination with ribavirin and/or amantadine for the treatment of chronic hepatitis C in non-responders to interferon monotherapy: a randomized trial. Journal of Viral Hepatitis 2007;14(2):89-95. [PUBMED: 17244248]
Sax 2001 {published data only}
  • Sax H, Friedl A, Renner E, Steuerwald MH, Weber R. Pilot study of interferon-alpha with and without amantadine for the treatment of hepatitis C in HIV coinfected individuals on antiretroviral therapy. Infection 2001;29(5):267-70. [PUBMED: 11688904]
Shakil 2000 {published data only}
  • Ahmad J, Vargas H, Balan V, Rakela J, Shakil AO. A randomized, double-blind, placebo-controlled trial of interferon-alpha and amantadine versus interferon-alpha alone in the treatment of patients with chronic hepatitis C. Digestive Diseases and Sciences 2002;47(7):1655-6.
  • Shakil AO, Balan V, Vargas H, Gartner K, Rakela J. A randomized, double-blind, placebo controlled trial of interferon-alfa and amantadine versus interferon-alfa alone in the treatment of chronic hepatitis C. Gastroenterology 2000;118:A1487.
Smith 2004 {published data only}
  • Smith JP, Riley TR 3rd, Devenyi A, Bingaman SI, Kunselman A. Amantadine therapy for chronic hepatitis C. Journal of General Internal Medicine 2004;19(6):662-8. [PUBMED: 15209605]
  • Smith JP, Riley TR 3rd, Devenyi A, Bingaman SI, Kunselman A. Amantadine therapy for chronic hepatitis C: a randomized double-blind placebo controlled trial. Gastroenterology 2002;122(S4):A-627.
Tabone 2001 {published data only}
  • Tabone M, Delmastro B, Bonardi R, Andreoni M, Manca A, Calleri G, et al. Combination therapy interferon plus amantadine in chronic active hepatitis C. A multicentric randomised study: preliminary reports. Hepatology 1999;30:628A.
  • Tabone M, Laudi C, Delmastro B, Biglino A, Andreoni M, Chieppa F, et al. Interferon and amantadine in combination as initial treatment for chronic hepatitis C patients. Journal of Hepatology 2001;35(4):517-21. [PUBMED: 11682037]
Teuber 2001 {published data only}
  • Teuber G, Berg T, Naumann U, Raedle J, Brinkmann S, Hopf U, et al. Randomized, placebo-controlled, double-blind trial with interferon-alpha with and without amantadine sulphate in primary interferon-alpha nonresponders with chronic hepatitis C. Journal of Viral Hepatitis 2001;8(4):276-83. [PUBMED: 11454179]
  • Teuber G, Naumann U, Berg T, Dreher A, Hopf U, Zeuzem S. Randomized, placebo-controlled, double-blind trial with interferon-A (IFN A) with and without amantadin-sulfat in primary IFN-A non-responders with chronic hepatitis C. Hepatology 2000;32:354A.
  • Teuber G, Naumann U, Berg T, Raedle J, Dreher A, Hopf U, et al. Multicenter, randomized, double-blind, placebo-controlled trial of interferon-A (IFN-A2A) with and without amantadine as treatment for IFN-A non-responders with chronic hepatitis C. Gastroenterology 2000;118:A1494.
Teuber 2002 {published data only}
  • Teuber G, Pascu M, Lafrenz M, Weidenbach H, Schoelmrich J, Wietske-Braun P, et al. Randomized, controlled trial with interferon-alfa plus ribavirin with and without amantadine sulphate in patients with chronic hepatitis C relapsing after primary successful antiviral treatment. Hepatology 2001;34:579A.
  • Teuber G, Pascu M, Lafrenz M, Weidenbach H, Schoelmrich J, Wietske-Braun P, et al. Randomized, controlled trial with interferon-alpha plus ribavirin with and without amantadine sulphate in patients with chronic hepatitis C relapsing after previous successful antiviral treatment. Journal of Hepatology 2002;36:132.
Teuber 2003 {published data only}
  • Teuber G, Berg T, Lafrenz M, Weidenbach H, Schoelmerich J, Wietzke-Braun P, et al. Randomized, controlled trial with interferon-alpha (IFN-alpha) combined with ribavirin with and without amantadine sulfate in primary IFN-alpha nonresponsive patients with chronic hepatitis C. Journal of Hepatology 2001;34(1):23.
  • Teuber G, Berg T, Lafrenz M, Weidenbach H, Schoelmerich J, Wietzke-Braun P, et al. Randomized, controlled trial with interferon-α (IFN-α) combined with ribavirin with and without amantadinsulfat in primary IFN-α non-responders with chronic hepatitis C. Hepatology 2001;120:A381.
  • Teuber G, Pascu M, Berg T, Lafrenz M, Pausch J, Kullmann F, et al. Randomized, controlled trial with IFN-alpha combined with ribavirin with and without amantadine sulphate in non-responders with chronic hepatitis C. Journal of Hepatology 2003;39(4):606-13. [PUBMED: 12971972]
Thuluvath 2004 {published data only}
  • Thuluvath PJ, Maheshwari A, Mehdi J, Fairbanks KD, Wu LL, Gelrud LG, et al. Randomised, double blind, placebo controlled trial of interferon, ribavirin, and amantadine versus interferon, ribavirin, and placebo in treatment naive patients with chronic hepatitis C. Gut 2004;53(1):130-5. [PUBMED: 14684587]
van Soest 2010 {published data only}
  • van Soest H, van der Schaar PJ, Koek GH, de Vries RA, van Ooteghem NA, van Hoek B, et al. No beneficial effects of amantadine in treatment of chronic hepatitis C patients. Digestive and Liver Disease 2010;42(7):496-502. [PUBMED: 20018575]
Vardar 2001 {published data only}
  • Vardar R, Karasu Z, Gunsar F, Akarca U, Ersoz G, Batur Y. Interferon plus amantadine has no superiority to IFN monotherapy in naive patients with chronic hepatitis C. Journal of Hepatology 2001;34:178.
von Wagner 2008 {published data only}
  • von Wagner M, Hofmann WP, Teuber G, Berg T, Goeser T, Spengler U, et al. Placebo-controlled trial of 400 mg amantadine combined with peginterferon alfa-2a and ribavirin for 48 weeks in chronic hepatitis C virus-1 infection. Hepatology 2008;48(5):1404-11. [PUBMED: 18846541]
  • von Wagner M, Hofmann WP, Teuber G, Berg T, Goeser T, Spengler U, et al. Randomized, double-blind, placebo-controlled trial of peginterferon alfa-2a (40KD) and ribavirin with and without 400 mg amantadine-sulphate for 48 weeks in treatment naive HCV genotype 1-infected patients. Hepatology 2007;46:342A-3A.
  • von Wagner M, Hofmann WP, Teuber G, Berg T, Goeser T, Spengler U, et al. Sustained virologic response is associated with worse QoL during and improved QoL after treatment with peginterferon alfa-2a and ribavirin. Hepatology 2008;48:886A-7A.
Wenger 2007 {published data only}
  • Wenger C, Bischof T, Gonvers JJ, Renner EL, Mullhaupt B. Interferon and ribavirin with or without amantadine for interferon non-responders with chronic hepatitis C. A randomized, controlled pilot study. Swiss Medical Weekly 2007;137(29-30):418-23. [PUBMED: 17705104]
Yang 2003 {published data only}
  • Yang SS, Tu TC, Wu CH, Chen DS. Combination of interferon alfa-2a and amantadine does not improve the efficacy of interferon therapy in patients with chronic hepatitis C. Hepato-Gastroenterology 2003;50(53):1575-8. [PUBMED: 14571789]
  • Yang SS, Tu TC, Wu CH, Chen DS. Combination of interferon alfa-2a and amantadine does not improve the efficacy of interferon therapy in patients with chronic hepatitis C. Hepatology 1999;30:369A.
Zeuzem 2000 {published data only}
  • Zeuzem S, Teuber G, Naumann U, Berg T, Raedle J, Hartmann S, et al. Randomised, double-blind, placebo-controlled trial of interferon-alfa with and without amantadine as initial treatment for chronic hepatitis C. Hepatology 1999;30:200A.
  • Zeuzem S, Teuber G, Naumann U, Berg T, Raedle J, Hartmann S, et al. Randomized, double-blind, placebo-controlled trial of interferon alfa2a with and without amantadine as initial treatment for chronic hepatitis C. Hepatology 2000;32(4 Pt 1):835-41. [PUBMED: 11003631]

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Buggisch 2009 {published data only}
  • Buggisch P, Zeuzem S, Teuber G, Möller B, Ehrhardt A, Gelbmann C, et al. Treating relapse with peginterferon alfa-2a plus ribavirin and amantadin for either 72 or 48 weeks (in patients with HDV-type 1/3 infection): results from the TRELA-study. Journal of Hepatology 2009;50(S1):S382.
Di Bisceglie 2001 {published data only}
  • Di Bisceglie AM, Bernstein DE, Rustgi VR, Gitlin N, Jeffers LJ, Simon D, et al. Pegylated (40 KDA) interferon alfa-2a (Pegasys®) in new combination therapies: a report of a randomized, multicenter efficacy and safety study. Journal of Hepatology 2001;34:143.
Mendez-Navarro 2010a {published data only}
  • Mendez-Navarro J, Chirino RA, Corey KE, Gorospe EC, Zheng H, Moran S, et al. Erratum: a randomized controlled trial of double versus triple therapy with amantadine for genotype 1 chronic hepatitis C in Latino patients. Digestive Diseases and Sciences 2010;55(10):3010.
Nakamura 2003 {published data only}
  • Nakamura H, Uyama H, Enomoto H, Kishima Y, Yamamoto M, Yoshida K, et al. The combination therapy of interferon and amantadine hydrochloride for patients with chronic hepatitis C. Hepato-Gastroenterology 2003;50(49):222-6. [PUBMED: 12630027]
Popovic 2000 {published data only}
  • Popovic A, Vian A, Lorenzoni U, Lobello S, Pevere S, Silverij E, et al. Daily interferon monotherapy versus daily interferon plus amantadine in the treatment of naive chronic hepatitis C patients: short-term response. Journal of Hepatology. 2000; Vol. 32:195.
Quarantini 2006 {published data only}
  • Quarantini LC, Miranda-Scippa A, Schinoni MI, Sampaio AS, Santos-Jesus R, Bressan RA, et al. Effect of amantadine on depressive symptoms in chronic hepatitis C patients treated with pegylated interferon: a randomized, controlled pilot study. Clinical Neuropharmacology 2006;29(3):138-43. [PUBMED: 16772812]
Schories 2003 {published data only}
  • Schories M, Kallinowski B, Goeser T, Maier KP, Lutterer A, Wietzke-Braun V, et al. Randomized placebo controlled double blind study in patients with chronic hepatitis C who did not respond to interferon therapy: comparison between interferon A, ribavirin +/- amantadine. Journal of Hepatology 2003;38:164.
  • Schories M, Kallinowski B, Goeser T, Maier KP, Wietzke-Braun V, Lutterer A, et al. Randomized placebo controlled double blind study in interferon nonresponder chronic hepatitis C patients with interferon A, ribavirin, amantadine in comparison to interferon A and ribavirin. Hepatology 2002;36(4):572A.
Torre 1999 {published data only}
  • Torre F, Brizzolara R, Giusto R, Grasso A, Sinelli N, Campo N, et al. HCV-RNA dynamics in the first month of treatment with IFN daily therapy alone versus combinations with amantadine or ribavirin. Journal of Hepatology 1999;30:128.
Zilly 2002 {published data only}
  • Zilly M, Lingenauber C, Desch S, Vath T, Klinker H, Langmann P. Triple antiviral re-therapy for chronic hepatitis C with interferon-alpha, ribavirin and amantadine in nonresponders to interferon-alpha and ribavirin. European Journal of Medical Research 2002;7(4):149-54. [PUBMED: 12010649]

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Altman 2003
Alves Galvão 2012
Asselah 2010
Awad 2010
Bacon 2011
  • Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. New England Journal of Medicine 2011;364(13):1207-17. [PUBMED: 21449784]
Brok 2008
  • Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. Journal of Clinical Epidemiology 2008;61(8):763-9.
Brok 2009
Brok 2009a
  • Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta-analyses may be inconclusive - Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. International Journal of Epidemiology 2009;38(1):287-98.
Brok 2010
Chen 2012
  • Chen J, Shi J, Xie WF, Zeng X, Lin Y. Meta-analysis: amantadine may lower the efficacy of pegylated interferon plus ribavirin in treatment-naive hepatitis C genotype 1 patients. International Journal of Infectious Diseases 2012;16(10):e748-52. [PUBMED: 22836046]
Choo 1989
Chutaputti 2000
Crosby 2009
  • Crosby N, Deane KH, Clarke CE. Amantadine in Parkinson's disease. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD003468]
CTU 2011
  • Copenhagen Trial Unit. TSA - Trial Sequential Analysis. ctu.dk/tsa/ 2011 (accessed 4 September 2013).
Davis 1989
  • Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC Jr, Perrillo RP, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. New England Journal of Medicine 1989;321(22):1501-6. [PUBMED: 2509916]
Davis 1998
  • 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. International Hepatitis Interventional Therapy Group. New England Journal of Medicine 1998;339(21):1493-9. [PUBMED: 9819447]
De Clercq 2001
Deltenre 2004
  • Deltenre P, Henrion J, Canva V, Dharancy S, Texier F, Louvet A, et al. Evaluation of amantadine in chronic hepatitis C: a meta-analysis. Journal of Hepatology 2004;41(3):462-73. [PUBMED: 15336450]
DeMets 1987
DerSimonian 1986
Di Bisceglie 2011
Di Martino 2011
EASL 2011
  • European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. Journal of Hepatology 2011;55(2):245-64. [PUBMED: 21371579]
Egger 1997
Egger 2003
  • Egger M, Juni P, Bartlett C, Holenstein F, Sterne J. How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study. Health Technology Assessment 2003;7(1):1-76. [PUBMED: 12583822]
El-Serag 2003
  • El-Serag HB, Davila JA, Petersen NJ, McGlynn KA. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Annals of Internal Medicine 2003;139(10):817-23. [PUBMED: 14623619]
Ghany 2009
Gluud 1998
Gluud 2007
Gluud 2014
  • Gluud C, Nikolova D, Klingenberg SL, Alexakis N, Als-Nielsen B, Colli A, et al. Cochrane Hepato-Biliary Group. About The Cochrane Collaboration (Cochrane Review Groups (CRGs)). 2014, Issue 1. Art. No.: LIVER.
Gurusamy 2013
  • Gurusamy KS, Wilson E, Koretz RL, Allen VB, Davidson BR, Burroughs AK, et al. Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?. PloS One 2013;8(12):e83313. [PUBMED: 24349487]
Guyatt 2008
  • Guyatt G, Oxman AD, Vist GE, Kunz R, Falck Y, Alonso CP, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ (Clinical Research Ed.) 2008;336(7650):924-6.
Hauser 2014
Hauser 2014a
  • Hauser G, Awad T, Thorlund K, Štimac D, Mabrouk M, Gluud C. Peginterferon alpha-2a versus peginterferon alpha-2b for chronic hepatitis C. Cochrane Database of Systematic Reviews 2014, Issue 2. [DOI: 10.1002/14651858.CD005642.pub3]
Higgins 2002
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Hollis 1999
ICH-GCP 1997
  • International Conference on Harmonisation Expert Working Group. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Guideline for good clinical practice 1997 CFR & ICH Guidelines. Vol. 1, PA 19063-2043, USA: Barnett International/PAREXEL, 1997.
Jacobson 2011
  • Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. New England Journal of Medicine 2011;364(25):2405-16. [PUBMED: 21696307]
Jefferson 2012
  • Jefferson T, Demicheli V, Di Pietrantonj C, Rivetti D. Amantadine and rimantadine for influenza A in adults. Cochrane Database of Systematic Reviews 2012, Issue 7. [DOI: 10.1002/14651858.CD001169.pub3]
Kenny-Walsh 1999
  • Kenny-Walsh E. Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group. New England Journal of Medicine 1999;340(16):1228-33. [PUBMED: 10210705]
Kim 2009
  • Kim WR, Terrault NA, Pedersen RA, Therneau TM, Edwards E, Hindman AA, et al. Trends in waiting list registration for liver transplantation for viral hepatitis in the United States. Gastroenterology 2009;137(5):1680-6. [PUBMED: 19632234]
Kjaergard 1999
Kjaergard 2001
Koff 1980
Koretz 1993
Koretz 2013
Lauer 2001
Lavanchy 2011
Lim 2005
Lundh 2012
McHutchison 1998
  • 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. Hepatitis Interventional Therapy Group. New England Journal of Medicine 1998;339(21):1485-92. [PUBMED: 9819446]
Moher 1998
  • Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?. Lancet 1998;352:609-13.
Myers 2002
  • Myers RP, Regimbeau C, Thevenot T, Leroy V, Mathurin P, Opolon P, et al. Interferon for interferon naive patients with chronic hepatitis C. Cochrane Database of Systematic Reviews 2002, Issue 2. [DOI: 10.1002/14651858.CD000370]
Needleman 1999
Poordad 2011
  • Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, et al. Boceprevir for untreated chronic HCV genotype 1 infection. New England Journal of Medicine 2011;364(13):1195-206. [PUBMED: 21449783]
Poynard 1998
  • 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. International Hepatitis Interventional Therapy Group (IHIT). Lancet 1998;352(9138):1426-32. [PUBMED: 9807989]
Reichard 1991
Reichard 1993
RevMan 2012 [Computer program]
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Rodger 2000
Royle 2003
  • Royle P, Milne R. Literature searching for randomised controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591-603.
Savović 2012
  • Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Health Technology Assessment 2012;16(35):1-82.
Savović 2012a
  • Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Annals of Internal Medicine 2012;157(6):429-38.
Schultz 1995
  • Schultz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408-12.
Schulz 2012
  • Schulz KF, Altman DG, Moher D, for the CONSORT Group. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Internal Journal of Surgery 2011;9(8):672-7.
Seeff 2009
Sherman 2011
  • Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, Everson GT, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. New England Journal of Medicine 2011;365(11):1014-24. [PUBMED: 21916639]
Simin 2007
Simmonds 2005
Smith 2004a
  • Smith JP, Riley TR 3rd, Bingaman S, Mauger DT. Amantadine therapy for chronic hepatitis C: a dose escalation study. American Journal of Gastroenterology 2004;99(6):1099-104. [PUBMED: 15180732]
    Direct Link:
Soza 2002
SPIRIT 2013
  • Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 Statement: defining standard protocol items for clinical trials. Annals of Internal Medicine 2013;158:200-7.
SPIRIT 2013a
  • Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin J, et al. SPIRIT 2013 Explanation and Elaboration: Guidance for protocols of clinical trials. BMJ (Clinical Research Ed.) 2013;346:e7586.
Sulkowski 2004
Sy 2006
  • Sy T, Jamal MM. Epidemiology of hepatitis C virus (HCV) infection. International Journal of Medical Sciences 2006;3(2):41-6. [PUBMED: 16614741]
Thein 2008
Thorlund 2009
  • Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses. International Journal of Epidemiology 2009;38(1):276-86.
Thorlund 2010
  • Thorlund K, Anema A, Mills E. Interpreting meta-analysis according to the adequacy of sample size. An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV-infected individuals. Clinical Epidemiology 2010;2:57-66.
Thorlund 2011
  • Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C. User manual for Trial Sequential Analysis (TSA). ctu.dk/tsa/files/tsa_manual.pdf 2011 (accessed 23 September 2013).
Tine 1991
Ueno 2009
Wetterslev 2008
  • Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. Journal of Clinical Epidemiology 2008;61(1):64-75.
Wetterslev 2009
Wiese 2000
Wood 2008
  • Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ (Clinical Research Ed.) 2008;336(7644):601-5.
Zeuzem 2011