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Meta-Analysis
. 2013 Jan 31;2013(1):CD003617.
doi: 10.1002/14651858.CD003617.pub2.

Interferon for interferon nonresponding and relapsing patients with chronic hepatitis C

Ronald L Koretz  1 , Maria Pleguezuelo, Vasiliki Arvaniti, Pilar Barrera Baena, Ruben Ciria, Kurinchi Selvan Gurusamy, Brian R Davidson, Andrew K Burroughs
Affiliations
Meta-Analysis

Interferon for interferon nonresponding and relapsing patients with chronic hepatitis C

Ronald L Koretz et al. Cochrane Database Syst Rev. .

Abstract

Background: The widely-accepted treatment outcome for chronic hepatitis C is the sustained viral response (that is, no measurable viral RNA in blood six months after treatment). However, this surrogate outcome (as well as the previously employed biochemical and histologic ones) has never been validated. This situation exists because there are very few randomized clinical trials that have used clinical events (mortality or manifestations of decompensated cirrhosis) as outcomes, because those clinical events only occur after many years of infection. Patients in whom initial therapy fails to produce sustained viral responses do become potential candidates for retreatment; some of these individuals are not candidates for ribavirin or protease inhibitors and consideration could be given to retreatment with interferon alone.

Objectives: To assess the benefits and harms of interferon monotherapy retreatment in chronic hepatitis C patients and to validate the currently employed surrogate outcomes in this group of patients.

Search methods: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until 16 August 2012.

Selection criteria: Randomized trials comparing interferon versus placebo or no treatment in chronic hepatitis C nonresponders and relapsers to previous interferon.

Data collection and analysis: The primary outcomes were mortality (all-cause and hepatic), quality of life, and adverse events. Secondary outcomes were liver-related morbidity, sustained viral responses, biochemical responses, histologic improvements, and costs. We used both fixed-effect and random-effects model meta-analyses, reporting only the former if no difference existed.

Main results: Seven trials were identified. Two of them were at low risk of bias (the HALT-C and EPIC3 trials) and included 1676 patients. Both of these trials addressed the role of long-term low-dose pegylated interferon therapy in patients with severe fibrosis (demonstrated on liver biopsy) and were designed to assess the clinical outcomes. The remaining five trials included 300 patients and were at high risk of bias. Based on all trials reporting the outcomes, no significant difference was observed in either all-cause mortality (78/843 (9.3%) versus 62/867 (7.2%); risk ratio (RR) 1.30, 95% confidence interval (CI) 0.95 to 1.79; 3 trials) or hepatic mortality (41/532 (7.7%) versus 40/552 (7.2%); RR 1.07, 95% CI 0.70 to 1.63; 2 trials); however, when only the two trials at low risk of bias were combined, all-cause mortality was significantly higher in the recipients of the pegylated interferon (78/828 (9.4%) versus 57/848 (6.7%); RR 1.41, 95% CI 1.02 to 1.96) although trial sequential analysis could not exclude the possibility of random error. There was less variceal bleeding in the recipients of the interferon (4/843 (0.5%) versus 18/867 (2.1%); RR 0.24, 95% CI 0.09 to 0.67; 3 trials), although again trial sequential analysis could not exclude the presence of a type I error and the effect could not be confirmed in a random-effects model meta-analysis. No significant differences were seen with regard to the development of ascites, encephalopathy, hepatocellular carcinoma, or the need for liver transplantation. One trial reported quality of life data; the pain score was significantly worse in the recipients of the pegylated interferon. Adverse effects tended to be more common in the interferon recipients; the ones that were significantly more common included hematologic complications, infections, flu-like symptoms, and rash. The recipients of interferon had significantly more sustained viral responses (20/557 (3.6%) versus 1/579 (0.2%); RR 15.38, 95% CI 2.93 to 80.71; 4 trials) and a type I error was excluded by trial sequential analysis. The METAVIR activity score also improved (36/55 (65%) versus 20/46 (43.5%); RR 1.49, 95% CI 1.02 to 2.18; 2 trials). No significant differences were seen with regard to histologic fibrosis assessments.

Authors' conclusions: The clinical data were limited to patients with histologic evidence of severe fibrosis who were retreated with pegylated interferon. In this scenario, retreatment with interferon did not appear to provide significant clinical benefit and, when only the trials at low risk of bias were considered, retreatment for several years may even have increased all-cause mortality. Such treatment also produced adverse events. On the other hand, the treatment did result in improvement in some surrogate outcomes, namely sustained viral responses and histologic evidence of inflammation. Interferon monotherapy retreatment cannot be recommended for these patients. No clinical data are available for patients with less severe fibrosis. The sustained viral response cannot be used as a surrogate marker for hepatitis C treatment in this clinical setting with low sustained viral response rates and needs to be validated in others in which higher sustained viral response rates are reported.

PubMed Disclaimer

Conflict of interest statement

The authors have no permanent financial contracts with companies producing interferon.

Dr Barrera's research activity is partially supported by the Centro de Investigacion Biomedica en Red en Enfermedades Hepaticas y Digestivas (CIBERehd).

The authors have no other relevant affiliation or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript.

Figures

1
1
Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
2
2
Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.
3
3
Study flow diagram.
4
4
Trial sequential analysis for low risk of bias trials reporting all‐cause mortality. Assumptions were 1% mortality in control arm, RR = 0.50, alpha error 5%, power 80%. The required information size was 9349 patients.
5
5
Trial sequential analysis for low risk of bias trials reporting rates of variceal bleeding in both groups. Assumptions were 2% incidence in control arm, RR = 0.50, alpha error 5%, power 80%.The required information size was 8537 patients.
6
6
Trial sequential analysis in trials reporting sustained viral response rates in both arms. Assumptions were 0.5% in controls, 3% in treated arms, alpha error 5%, power 80%. However, the required information size (864) was exceeded and using lower assumption of rate in controls or higher in treated patients only further reduced the required information size.
1.1
1.1. Analysis
Comparison 1 Interferon versus control mortality, Outcome 1 All‐cause mortality.
1.2
1.2. Analysis
Comparison 1 Interferon versus control mortality, Outcome 2 Liver‐related mortality.
3.1
3.1. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 1 Any adverse events.
3.2
3.2. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 2 Serious adverse events.
3.3
3.3. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 3 Hematologic.
3.4
3.4. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 4 Psychiatric events.
3.5
3.5. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 5 Infections.
3.6
3.6. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 6 Gastrointestinal.
3.7
3.7. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 7 Systemic symptoms.
3.8
3.8. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 8 Cardiopulmonary.
3.9
3.9. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 9 Musculoskeletal.
3.10
3.10. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 10 Dermatologic.
3.11
3.11. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 11 Metabolic.
3.12
3.12. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 12 Neoplasms.
3.13
3.13. Analysis
Comparison 3 Interferon versus control ‐ adverse events, Outcome 13 Other system adverse events.
4.1
4.1. Analysis
Comparison 4 Interferon versus control ‐ liver‐related morbidity, Outcome 1 Hepatic encephalopathy.
4.2
4.2. Analysis
Comparison 4 Interferon versus control ‐ liver‐related morbidity, Outcome 2 Variceal bleeding.
4.3
4.3. Analysis
Comparison 4 Interferon versus control ‐ liver‐related morbidity, Outcome 3 Ascites.
4.4
4.4. Analysis
Comparison 4 Interferon versus control ‐ liver‐related morbidity, Outcome 4 Spontaneous bacterial peritonitis.
4.5
4.5. Analysis
Comparison 4 Interferon versus control ‐ liver‐related morbidity, Outcome 5 Hepatocellular carcinoma.
4.6
4.6. Analysis
Comparison 4 Interferon versus control ‐ liver‐related morbidity, Outcome 6 Liver transplantation.
4.7
4.7. Analysis
Comparison 4 Interferon versus control ‐ liver‐related morbidity, Outcome 7 Decompensated cirrhosis.
5.1
5.1. Analysis
Comparison 5 Interferon versus control ‐ progression of Child‐Pugh‐Turcotte score, Outcome 1 Progression of score.
6.1
6.1. Analysis
Comparison 6 Interferon versus control ‐ surrogate outcomes, Outcome 1 Sustained viral response.
6.3
6.3. Analysis
Comparison 6 Interferon versus control ‐ surrogate outcomes, Outcome 3 Improvement in METAVIR activity score.
6.4
6.4. Analysis
Comparison 6 Interferon versus control ‐ surrogate outcomes, Outcome 4 Progression to cirrhosis.
6.5
6.5. Analysis
Comparison 6 Interferon versus control ‐ surrogate outcomes, Outcome 5 Improvement in METAVIR fibrosis score.
6.6
6.6. Analysis
Comparison 6 Interferon versus control ‐ surrogate outcomes, Outcome 6 Sustained viral response ‐ only full papers.
8.1
8.1. Analysis
Comparison 8 Interferon versus control mortality ‐ low risk of bias trials, Outcome 1 Liver‐related mortality.
8.2
8.2. Analysis
Comparison 8 Interferon versus control mortality ‐ low risk of bias trials, Outcome 2 All‐cause mortality.
9.1
9.1. Analysis
Comparison 9 Interferon versus control ‐ liver‐related morbidity ‐ low risk of bias trials, Outcome 1 Hepatic encephalopathy.
9.2
9.2. Analysis
Comparison 9 Interferon versus control ‐ liver‐related morbidity ‐ low risk of bias trials, Outcome 2 Variceal bleeding.
9.3
9.3. Analysis
Comparison 9 Interferon versus control ‐ liver‐related morbidity ‐ low risk of bias trials, Outcome 3 Ascites.
9.4
9.4. Analysis
Comparison 9 Interferon versus control ‐ liver‐related morbidity ‐ low risk of bias trials, Outcome 4 Spontaneous bacterial peritonitis.
9.5
9.5. Analysis
Comparison 9 Interferon versus control ‐ liver‐related morbidity ‐ low risk of bias trials, Outcome 5 Hepatocellular carcinoma.
9.6
9.6. Analysis
Comparison 9 Interferon versus control ‐ liver‐related morbidity ‐ low risk of bias trials, Outcome 6 Liver transplantation.
11.1
11.1. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 1 Any adverse events.
11.2
11.2. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 2 Serious adverse events.
11.3
11.3. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 3 Haematologic.
11.4
11.4. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 4 Psychiatric events.
11.5
11.5. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 5 Infections.
11.6
11.6. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 6 Gastrointestinal.
11.7
11.7. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 7 Systemic symptoms.
11.8
11.8. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 8 Cardiopulmonary.
11.9
11.9. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 9 Musculoskeletal.
11.10
11.10. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 10 Dermatologic.
11.11
11.11. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 11 Metabolic.
11.12
11.12. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 12 Neoplasms.
11.13
11.13. Analysis
Comparison 11 Interferon versus control ‐ adverse events ‐ low risk of bias trials, Outcome 13 Other system adverse events.
12.1
12.1. Analysis
Comparison 12 Interferon versus control ‐ progression of Child‐Pugh‐Turcotte score ‐ low risk of bias trials, Outcome 1 Progression of score.
13.1
13.1. Analysis
Comparison 13 Interferon versus control ‐ surrogate outcomes ‐ low risk of bias trials, Outcome 1 Sustained viral response.
13.4
13.4. Analysis
Comparison 13 Interferon versus control ‐ surrogate outcomes ‐ low risk of bias trials, Outcome 4 Progression to cirrhosis.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Alric 2001 {published data only}
    1. Alric L, Duffaut M, Selves J, Sandre K, Mularczyck M, Izopet J, et al. Maintenance therapy with gradual reduction of the interferon dose over one year improves histological response in patients with chronic hepatitis C with biochemical response: results of a randomized trial. Journal of Hepatology 2001;35:272‐8. - PubMed
Bresci 1995 {published data only}
    1. Bresci G, Parisi G, Banti S, Capzia A. Re‐treatment of interferon‐resistant patients with chronic hepatitis C with interferon‐alpha. Journal of Viral Hepatitis 1995;2(3):155‐8. [MEDLINE: ] - PubMed
Bruix 2011 {published data only}
    1. Bruix J, Poynard T, Colombo M, Schiff E, Burak K, Heathcote EJ, et al. Maintenance therapy with peginterferon alfa‐2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C. Gastroenterology 2011;140(6):1990‐9. [DOI: 10.1053/j.gastro.2011.03.010] - DOI - PubMed
    1. Bruix J, Poynard T, Colombo M, Schiff ER, Reichen J, Burak KW, et al. Final results of the EPIC3 cirrhosis maintenance trial: pegintron maintenance therapy in cirrhotic (METAVIR F4) HCV patients, who failed to respond to interferon/ribavirin (IR) therapy. Gastroenterology 2009;136 Suppl 1:A798.
    1. Poynard T, Munteanu M, Colombo M, Bruix J, Schiff ER, Terg R, et al. Impact of peginterferon maintenance therapy on biomarkers (Fibrotest [FT]‐Acitest [AT]) in cirrhotic (METAVIR F4) HCV prior non‐responders. Results from the EPIC3 cirrhosis maintenance trial. Hepatology 2009;50(4 Suppl):711A.
Di Bisceglie 2008 {published data only}
    1. Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC, et al. Prolonged therapy of advanced chronic hepatitis C with low‐dose peginterferon. New England Journal of Medicine 2008;359(23):2429‐41. - PMC - PubMed
    1. Bisceglie AM, Stoddard AM, Dienstag JL, Shiffman ML, Seeff LB, Bonkovsky HL, et al. Excess mortality in patients with advanced chronic hepatitis C treated with long‐term peginterferon. Hepatology 2011;53(4):1100‐8. - PMC - PubMed
    1. Hoefs JC, Everson GT, Shiffman ML, Morgan T, Chen W‐P, Gillen D. Is the platelet count determined by hepatic function or hypersplenism: Results of the HALT‐C trial?. Hepatology 2011;54(Suppl 1):582a‐3a.
    1. Hoefs JC, Shiffman ML, Goodman ZD, Kleiner DE, Dienstag JL, Stoddard AM, HALT‐C Trial Group. Rate of progression of hepatic fibrosis in patients with chronic hepatitis C: results from the HALT‐C Trial. Gastroenterology 2011;141(3):900‐8. - PMC - PubMed
    1. Lok AS, Everhard JE, Wright EC, Bisceglie AM, Kim H‐Y, Sterling RK, et al. Maintenance peginterferon therapy and other factors associated with hepatocellular carcinoma in patients with advanced hepatitis C. Gastroenterology 2011;3:840‐9. - PMC - PubMed
Shiffman 1999 {published data only}
    1. Shiffman ML, Hofmann CM, Contos MJ, Luketic VA, Sanyal AJ, Sterling RK, et al. A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia. Gastroenterology 1999;117(5):1164‐72. [MEDLINE: ] - PubMed
Tanwar 2012 {published data only (unpublished sought but not used)}
    1. Tanwar S, Wright M, Foster G, Ryder S, Mills P, Cramp M, et al. PACIFIC: A phase III, randomized, multicentre, dose escalation, efficacy and safety study examining the effects of treatment with peginterferon alfa‐2a in patients with Child's A or B cirrhosis in chronic hepatitis C virus infection. Gut 2010;59 Suppl 2:A38‐9.
    1. Tanwar S, Wright M, Foster GR, Ryder SD, Mills PR, Cramp ME, et al. PACIFIC: A phase III, randomized, multicenter, dose escalation, efficacy and safety study examining the effects of treatment with peginterferon alfa‐2a in patients with Child's A or B cirrhosis in chronic hepatitis C virus infection. Hepatology 2010;52(4 Suppl):710A.
    1. Tanwar S, Wright M, Foster GR, Ryder SD, Mills PR, Cramp ME, et al. Randomized clinical trial: a pilot study investigating the safety and effectiveness of an escalating dose of peginterferon α‐2a monotherapy for 48 weeks compared with standard clinical care in patients with hepatitis C cirrhosis. European Journal of Gastroenterology and Hepatology 2012;24(5):543‐50. - PubMed
Vaccaro 1997 {published data only}
    1. Vaccaro A, Giunta M, Lo Iacono O, Craxi A. Retreatment with leukocite interferon of chronic hepatitis C patients non responders to recombinant interferon. Journal of Hepatology 1997;26 Suppl 1:S197.

References to studies excluded from this review

Adinolfi 2003 {published data only}
    1. 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 randomized trial. Gut 2003;52:701‐5. - PMC - PubMed
Aghemo 2012 {published data only}
    1. Aghemo A, Colombo M. Peginterferon maintenance therapy in patients with advanced hepatitis C to prevent hepatocellular carcinoma: The plot thickens. Journal of Hepatology 2012;56(1):276‐8. - PubMed
Akham 2011 {published data only}
    1. Akham SC, Gurel E, Sayan M. The sustained virologic response of nonresponder hepatitis C virus patients with retreatment. Indian Journal of Pathology and Microbiology 2011;54(1):81‐4. - PubMed
Alaimo 2006 {published data only}
    1. Alaimo G, Marco V, Ferraro D, Stefano R, Porrovecchio S, D'Angelo F, et al. Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype relapsed after interferon monotherapy: a randomized controlled trial. World Journal of Gastroenterology 2006;12(42):6861‐4. - PMC - PubMed
Alberti 1997 {published data only}
    1. Alberti A, Chemello L, Noventa F, Cavalletto L, Salvo G. Therapy of hepatitis C: re‐treatment with alpha interferon. Hepatology 1997;26(3 Suppl 1):137S‐42S. - PubMed
Almasio 1999 {published data only}
    1. Almasio P, DiMarco V, Bonura C, Fuschi P, Camma C, LoIacono O, et al. Retreatment of relapsers with chronic hepatitis C: the effect of dose doubling and of host and viral factors. Hepatology 1997;4(Pt 2):416A.
    1. Almasio PL, Marco V, Bonura C, Fuschi P, Camma C, Lo Iacono O, et al. Viral and host factors in determining response of relapsers with chronic hepatitis C to retreatment with interferon. Digestive Diseases and Sciences 1999;44(5):1013‐9. [MEDLINE: ] - PubMed
    1. Fuschi P, Almasio P, Marco V, Camma C, Bonnura C, Lo Iacono O, et al. Should patients with chronic hepatitis C who relapse after interferon (IFN) be retreated?. Journal of Hepatology 1996;26 Suppl 1:S192.
Andreone 1999 {published data only}
    1. Andreone P, Gramenzi A, Cursaro C, Sbolli G, Fiorino S, 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. - PubMed
Andreone 2000 {published data only}
    1. Andreone P, Cusaro C, Gramenzi M, Margotti M, Ferr E, Talarico S, et al. High dose of interferon plus ribavirin for 6 or 12 months in non responder patients with chronic hepatitis C: results of a randomized trial. Journal of Hepatology 2000;32 Suppl 2:115.
Arase 1994 {published data only}
    1. Arase Y, Kumada H, Chayama K, Tsubota A, Koida I, Ikeda K, et al. Interferon retreatment of nonresponders with HCV‐RNA‐positive chronic hepatitis C. Journal of Gastroenterology 1994;29(3):299‐304. [MEDLINE: ] - PubMed
Arase 2003 {published data only}
    1. Arase Y, Ikeda K, Tsubota A, Suzuki Y, Saitoh S, Kobayashi M, et al. Efficacy of prolonged interferon therapy for patients with chronic hepatitis C with HCV‐genotype 1b and high virus load. Journal of Gastroenterology 2003;38(2):158‐63. - PubMed
    1. Arase Y, Ikeda K, Tsubota A, Suzuki Y, Saitoh S, Kobayashi M, et al. Randomized trial of prolonged interferon retreatment for chronic hepatitis C patients with HCV‐genotype 1b and high virus load. Hepatology Research 2003;25:364‐70. - PubMed
August‐Jörg 2003 {published data only}
    1. August‐Jörg BS, Borivicka J, Dufour JF, Gonvers JJ, Henz S, Hermann S, et al. Twenty‐four vs. forty‐eight weeks of re‐therapy with interferon alpha 2b and ribavirin in interferon alpha monotherapy relapsers with chronic hepatitis C. Swiss Medical Weekly 2003;133:455‐60. - PubMed
Azzaroli 2004 {published data only}
    1. Azzaroli F, Accogli E, Nigro G, Trere D, Giovanelli S, Miracolo A, et al. Interferon plus ribavirin and interferon alone in preventing hepatocellular carcinoma: a prospective study on patients with HCV related cirrhosis. World Journal of Gastroenterology: WJG 2004;10(21):3099‐102. - PMC - PubMed
Bapin 2004 {published data only}
    1. Bapin C, Fabbro‐Peray P, Hachemane S, Blanc F, Diaz D, Pueyo P, et al. Retreatment with pegylated interferon alpha‐2b and ribavirin in patients with chronic hepatitis C non responders to interferon monotherapy or interferon and ribavirin combination. A prospective randomized pilot study of two regimens: induction versus Peg. Journal of Hepatology 2004;40 Suppl 1:135.
Barbaro 1998 {published data only}
    1. Barbaro G, 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 Journal of Gastroenterology 1998;93(12):2445‐51. - PubMed
Barbaro 1999 {published data only}
    1. Barbaro G, Lorenzo G, Soldini M, Giancaspro G, Pellicelli A, Grisorio B, et al. Intravenous recombinant interferon‐beta versus interferon‐alpha‐2b and ribavirin in combination for short‐term treatment of chronic hepatitis C patients not responding to interferon‐alpha. Multicenter Interferon Beta Italian Group Investigators. Scandinavian Journal of Gastroenterology 1999;34(9):928‐33. - PubMed
Barbaro 1999 b {published data only}
    1. Barbaro G, Lorenzo G, Belloni G, Ferrari L, Paiano A, 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. - PubMed
Bekkering 1998 {published data only}
    1. Bekkering FC, Brouwer JT, Leroux‐Roels G, Vlierberghe H, Elewaut A, Schalm SW. Ultrarapid hepatitis C virus clearance by daily high‐dose interferon in non‐responders to standard therapy. Journal of Hepatology 1998;28(6):960‐4. - PubMed
Bell 1999 {published data only}
    1. 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. CONSTRUCT Group. Scandinavian Journal of Gastroenterology 1999;34(2):194‐8. - PubMed
Bellobuono 1997 {published data only}
    1. Bellobuono A, Mondazzi L, Tempini S, Silini E, Vicari F, Ideo 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. - PubMed
Berg 2006 {published data only}
    1. Berg T, Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, et al. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon‐alfa‐2a plus ribavirin. Gastroenterology 2006;130(4):1086‐97. - PubMed
Bergmann 2007 {published data only}
    1. Bergmann JF, Vrolijk JM, Schaar P, Vroom B, Hoek B, Sluys Veer A, et al. Gamma‐glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon‐alfa‐2b in chronic hepatitis C non‐responders. Liver International 2007;27(9):1217‐25. - PubMed
Bernardinello 1999 {published data only}
    1. Bernardinello E, Cavalletto L, Chemello L, Mezzocolli I, Donada C, Benvegnú L, et al. Long‐term clinical outcome after beta‐interferon therapy in cirrhotic patients with chronic hepatitis C. TVVH Study Group. Hepato‐Gastroenterology 1999;46:3216‐22. - PubMed
Böcher 2006 {published data only}
    1. Böcher WO, Schuchmann M, Link R, Heribert H, Rahman F, Sprinzl M, et al. Consensus interferon and ribavirin for patients with chronic hepatitis C and failure of previous interferon alfa therapy. Liver International 2006;26:319‐25. - PubMed
Bonkovsky 1996 {published data only}
    1. Bonkovsky HL, Clifford BD, Smith LJ, Allan C, Banner B. High‐dose interferon‐alpha 2b for re‐treatment of nonresponders or relapsing patients with chronic hepatitis C. A controlled randomized trial. Digestive Disease and Sciences 1996;41(1):149‐54. [MEDLINE: ] - PubMed
Bresci 2000 {published data only}
    1. Bresci G, Parisi G, Bertoni M, Capria A. High‐dose interferon plus ribavirin in chronic hepatitis C not responding to recombinant alpha‐interferon. Digestive and Liver Disease 2000;32(8):703‐7. - PubMed
Bresci 2000b {published data only}
    1. 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):75‐8. - PubMed
Brillanti 1994 {published data only}
    1. Brillanti S, Garson J, Foli M, Whitby K, Deaville R, Masci C, et al. A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa‐resistant chronic hepatitis C. Gastroenterology 1994;107(3):812‐7. - PubMed
Brillanti 1995 {published data only}
    1. Brillanti S, Miglioli M, Barbara L. Combination antiviral therapy with ribavirin and interferon alfa in interferon alfa relapsers and non‐responders: Italian experience. Journal of Hepatology 1995;23 Suppl 2:13‐5. - PubMed
Buti 2000 {published data only}
    1. Buti M, Olive G, Stalgis C, Estaban R, Guardi J. Quantification of serum hepatitis C virus RNA with daily or standard interferon doses plus ribavirin in nonresponder patients with chronic hepatitis C. Digestive Diseases and Sciences 2000;45(4):685‐9. - PubMed
Cagnoni 1999 {published data only}
    1. Cagnoni C, Pancotti D, Carrara G. The retreatment with natural leukocyte interferon alfa‐n3 of chronic hepatitis C patients: the intolerant and nonresponsive results to prior treatment with recombinant alfa interferon. Annali of Italiani di Medicina Interna 1999;14(3):159‐65. - PubMed
Carr 2007 {published data only}
    1. Carr C, Blaine‐Hollinger F, Yoffe B, Wakil A, Phillips J, Bzowej N, et al. Efficacy of interferon alpha‐2b induction therapy before retreatment for chronic hepatitis C. Liver International 2007;27(8):1111‐8. - PubMed
Carrara 1998 {published data only}
    1. Carrara M, Azzurro M, Adamo S. Retreatment with human leukocyte interferon alpha of chronic hepatitis C, recurring after a first cycle with recombinant interferon (Letter). Italian Journal of Gastroenterology and Hepatology 1998;30(2):234‐5. - PubMed
Cavalletto 2000 {published data only}
    1. 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. - PubMed
Chapman 2001 {published data only}
    1. Chapman BA, Stace NH, Edgar CL, Bartlett SE, Frampton CM, Scahill SL, et al. Interferon‐alpha2a/ribavirin versus interferon‐alpha2a alone for the retreatment of hepatitis C patients who relapse after a standard course of interferon. New Zealand Medical Journal 2001;114(1128):103‐4. - PubMed
Chemello 1997 {published data only}
    1. Chemello L, Cavalletto L, Donada C, Bonetti P, Casarin P, Urban F, et al. Efficacy of a second cycle of interferon therapy in patients with chronic hepatitis C. Gastroenterology 1997;113(5):1654‐9. [MEDLINE: ] - PubMed
Chousterman 2003 {published data only}
    1. Chousterman M, Auray‐Cartier V, Hagege H, Arpurt JP, Cassan P, Denis J, et al. Efficacy of pegylated interferon alfa‐2b in combination with ribavirin in patients with chronic hepatitis C non‐responders to a previous treatment. Journal of Hepatology 2003;38 Suppl 2:133.
COPILOT 2008 {published data only}
    1. Afdahl N, Freilich B, Levine R, Black M, Monsour H, O'Brien M. Colchicine versus peg‐intron long term (COPILOT) trial: interim analysis of clinical outcomes at year 2. (Abstract). Hepatology 2004;4 Suppl 1:239A.
    1. Afdahl NH, Levine R, Brown R, Freilich B, O'Brien M, Brass C, et al. Colchicine versus peg‐interferon alfa 2b long term therapy: results of the 4 year COPILOT trial. Journal of Hepatology 2008;48 Suppl 2:S4.
    1. Cardenas A, Pritchett S, Brown RS, Levine RA, Curry MP, Afdahl NH. The effects of long term PEG‐Interferon therapy on the development of esophageal varices and variceal bleeding in patients with hepatitis C and advanced fibrosis: Final results from the Copilot trial (Abstract). Gastroenterology 2009;136 Suppl 1:259.
Cornberg 2006 {published data only}
    1. Cornberg M, Hadem J, Herrmann E, Schuppert F, Schmidt HJ, Reiser M, et al. Treatment with daily consensus interferon plus ribavirin in non‐responder patients with chronic hepatitis C: a randomized open‐label pilot study. Journal of Hepatology 2006;44:291‐301. - PubMed
Cotler 1997 {published data only}
    1. Cotler SJ, Albert DG, Rosenblate HJ, Ganger DR, Jensen DM. Interferon therapy for chronic hepatitis C is associated with sustained histological improvement in virological nonresponders (NR) and responders with relapse (RR) (EASL abstract). Journal of Hepatology 1997;26 Suppl 1:S225.
Cuccorese 2000 {published data only}
    1. Cuccorese G, Tursi A, Spinazzola AM, Modeo ME, Miglietta A. Biochemical and virological changes in serum of nonresponder or relapser chronic hepatitis C patients retreated with interferon and ribavirin followed by interferon alone. American Journal of Gastroenerology 2000;95(9):2399‐400. - PubMed
Davis 1998 {published data only}
    1. 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
Davis 1999 {published data only}
    1. Davis GL, Schiff E, Marcellin P, Esteban Mur R, Goodman Z, Harvey J, et al. Long‐term continuous recombinant interferon alfa‐2b (Intron A) versus repeated 24‐week cycles for disease suppression in IFN‐relapsers with chronic hepatitis C (Abstract). Hepatology 1999;30(4 Pt 2):317A.
Diago 2007 {published data only}
    1. Diago M, Crespo J, Olveira A, Perez R, Barcena R, Sanchez‐Tapias JM, et al. Clinical trial: pharmacodynamics and pharmacokinetics of re‐treatment with fixed‐dose induction of peginterferon alfa‐2a in hepatitis C virus genotype 1 true non‐responder patients. Alimentary Pharmacology & Therapeutics 2007;26:1131‐8. - PubMed
Di Biceglie 2000 {published data only}
    1. Bisceglie A, Bonkovsky HL, Chopra S, Flamm S, Reddy RK, Grace N, et al. Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: a multicenter, prospective, randomized, controlled trial. Hepatology 2000;32(1):135‐8. - PubMed
Di Bisceglie 2001 {published data only}
    1. Bisceglie AM, Thompson J, Smith‐Wilkaitis N, Brunt EM, Bacon BR. Combination of interferon and ribavirin in chronic hepatitis C: re‐treatment of nonresponders to interferon. Hepatology 2001;33(3):704‐7. - PubMed
Di Marco 2000 {published data only}
    1. Marco V, Almasio P, Vaccaro A, Ferraro D, Pietro P, Cataldo MG, et al. Combined retreatment of relapse of chronic hepatitis C with high‐dose alfa‐2‐b interferon plus ribavirin for 6 or 12 months. Journal of Hepatology 2000;33:456‐62. - PubMed
Dollinger 2005 {published data only}
    1. Dollinger MM, Dridi Y, Lesske J, Behl S, Fleig WE. Efficacy of daily consensus interferon and ribavirin compared to peg‐interferon‐2b and ribavirin in non‐responders with chronic hepatitis C. Hepatology 2005;42(4):691A‐2A.
Enriquez 2000 {published data only}
    1. Enriquez J, Gallego A, Torras X, Perez‐Olmeda T, Diago M, Soriano V, et al. Retreatment for 24 vs 48 weeks with interferon‐alpha2b plus ribavirin of chronic hepatitis C patients who relapsed or did not respond to interferon alone. Journal of Viral Hepatitis 2000;7(6):403‐8. - PubMed
Erdem 2002 {published data only}
    1. Erdem L, Akbayir N, Cakaloglu Y, Cevikbas U, Badur S. Combination of interferon induction therapy and ribavirin in primary interferon non‐responders infected with genotype 1 hepatitis C virus. Journal of Hepatology 2002;36 Suppl 1:234.
Fargion 2006 {published data only}
    1. Fargion S, Borzio M, Maraschi A, Cargnel A. Triple antiviral therapy in HCV positive patients who failed prior combination therapy. World Journal of Gastroenterology 2006;12(33):5293‐300. - PMC - PubMed
Fartoux 2007 {published data only}
    1. Fartoux L, Degos F, Trepo C, Goria O, Cales P, Tran A, et al. Effect of prolonged Interferon therapy on the outcome of hepatitis C virus‐related cirrhosis: a randomized trial. Clinical Gastroenterology and Hepatology 2007;5:502‐7. - PubMed
Fattovich 2003 {published data only}
    1. Fattovich G, Zagni I, Minola E, Fabris P, Boccia S, Giusti, et al. Efficacy of prolonged 5 millions unit of interferon in combination with ribavirin for relapser patients with chronic hepatitis C. Journal of Viral Hepatitis 2003;10:111‐7. - PubMed
    1. Fattovich G, Zagni I, Ribero L, Castagnetti E, Minola E, Lomonaco L, et al. A randomized trial of prolonged high dose of interferon plus ribavirin for hepatitis C patients nonresponders to interferon alone. Journal of Viral Hepatitis 2004;11:543‐51. - PubMed
Ferenci 1996 {published data only}
    1. Ferenci P, Stauber R, Propst A, Fiedler R, Muller C, Gschwantler M, et al. Dose increase augments response rate to interferon‐alpha in chronic hepatitis C. Digestive Diseases and Sciences 1996;41(12 Suppl):103S‐8S. [MEDLINE: ] - PubMed
Fong 2000 {published data only}
    1. Fong TL, Pauly MP, Zacks S, Kahn JA, Sze G, Schulman D, et al. Multicenter randomized trial of 15 mcg Infergen administered daily vs. thrice weekly in patients with chronic hepatitis C who did not respond to interferon (IFN) therapy (abstract). Hepatology 2000;32(4 Pt 2):349A.
Fontagnes 2007 {published data only}
    1. Fontagnes T, Beorchia S, Douvin C, Delassalle P, Combis J.M, Hanslik B, et al. Safety and efficacy of combination therapy with peginterferon alfa‐2a (40kD) and ribavirin in the outpatient setting: prospective analysis of 197 patients with chronic hepatitis C viral infection. Gastroenterologie Clinique et Biologique 2007;31:566‐72. - PubMed
Gaeta 1997 {published data only}
    1. Gaeta GB, Virgilio D, Russo G, Stornaiuolo G, Nicolella U, Colella F, et al. Human leucocyte interferon‐alpha in chronic hepatitis C resistant to recombinant or lymphoblastoid interferon‐alpha: a randomized controlled trial. Journal of Viral Hepatitis 1997;4(3):209‐14. [MEDLINE: ] - PubMed
Gerken 1995 {published data only}
    1. Gerken G, Teuber G, Goergen B, Meyer zum Buschenfelde KH. Interferon‐alpha retreatment in chronic hepatitis C. Journal of Hepatology 1995;22(1 Suppl):118‐21. - PubMed
Getachew 2004 {published data only}
    1. Getachew Y, Browning JD, Prebis M, Rogers T, Brown GR. Combination therapy for the treatment of hepatitis C in the veteran population: higher than expected rates of therapy discontinuation. Alimentary Pharmacology & Therapeutics 2004;20:629‐36. - PubMed
Giudici‐Cipriani 1993 {published data only}
    1. Giudici‐Cipriani A, Azzola E, Varagona E, Vitali A, Marenco G, Conca V, et al. Usefulness of re‐treatment with interferon (IFN) in relapsing and non‐responder patients with chronic hepatitis C (Abstract). Journal of Hepatology 1993;18 Suppl 1:S123‐4.
Gross 1999 {published data only}
    1. Gross JB, Brandhagen DJ, Gossard AA, Poterucha JJ, Douglas DD, Spivey JR, et al. Daily interferon to suppress HCV viremia among interferon non‐responders (Abstract). Hepatology 1998;28(4 Pt 2):573A.
    1. Gross JB, Brandhagen DJ, Poterucha JJ, Lindor KD, Douglas DD, Spivey JR, et al. Interferon alpha 2b 5MU 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.
Guerret 1999 {published data only}
    1. Guerret S, Desmouliere A, Chossegros P, Costa AM, Badid C, Trepo C, et al. Long‐term administration of interferon‐alpha in non‐responder patients with chronic hepatitis C: follow‐up of liver fibrosis over 5 years. Journal of Viral Hepatitis 1999;6(2):125‐33. - PubMed
Hadziyannis 1997 {published data only}
    1. Hadziyannis AS, Papaioannou C, Spanou E, Manesis E, Hadziyannis SJ. Daily administration of interferon‐alpha for 1 month followed by a TIW standard regimen is associated with high response rates in chronic hepatitis C (Abstract). Hepatology 1997;26(4 Pt 2):420A.
Hasan 2001 {published data only}
    1. Hasan F, Asker H, al Shamali M, al Kalaoui M, al Nakib B. Interferon‐alpha plus ribavirin combination therapy for the treatment of chronic hepatitis C in interferon non‐responders. Hepato‐Gastroenterology 2000;47(36):1642‐4. - PubMed
Hass 2005 {published data only}
    1. Hass HG, Kreysel C, Fischinger J, Menzel J, Kaiser S. High‐dose interferon alfa‐2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non‐response or relapse after interferon alfa monotherapy. World Journal of Gastroenterology 2005;11(34):5342‐6. - PMC - PubMed
Heathcote 1998 {published data only}
    1. Heathcote EJ, Keeffe EB, Lee SS, Feinman SV, Tong MJ, Reddy KR, et al. Re‐treatment of chronic hepatitis C with consensus interferon. Hepatology 1998;27(4):1136‐43. [MEDLINE: ] - PubMed
    1. Heathcote JL, James S, Mullen KD, Hauser SC, Rosenblate H, Albert DG, et al. Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon. Hepatology 1999;30(2):562‐6. - PubMed
    1. Lee WM, Reddy KR, Tong MJ, Black M, Leeuwen DJ, Hollinger FB, et al. Early hepatitis C virus‐RNA predict interferon treatment outcomes in chronic hepatitis C. Hepatology 1998;28(5):1411‐5. - PubMed
Horiike 1994 {published data only}
    1. Horiike N, Kurose K, Ohkura I, Masumoto T, Nakanishi K, Michitaka K, et al. Retreatment with interferon in chronic hepatitis C (Letter). Journal of Hepatology 1994;21(6):1155. - PubMed
Iino 2002 {published data only}
    1. Iino S, Ichida F, Sakuma A. A randomized clinical trial with natural IFN‐alfa monotherapy for 24 or 48 weeks on patients with chronic hepatitis C having genotype 1b infection in high viral titers. Hepatology Research 2002;24(4):338‐45. - PubMed
Ikeda 1998 {published data only}
    1. Ikeda K, Kumada H, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, et al. A randomized controlled trial of interferon‐alpha in patients with cirrhosis caused by 2a/2b genotype hepatitis C virus. Journal of Hepatology 1998;28:910‐1. - PubMed
Ikeda 2000 {published data only}
    1. Ikeda F, Shimomura H, Miyake M, Fujioka SI, Itoh M, Takahashi A, et al. Early clearance of circulating hepatitis C virus enhanced by induction therapy with twice‐a‐day intravenous injection of IFN‐beta?. Journal of Interferon & Cytokine Research 2000;20(9):831‐6. - PubMed
Imai 1997 {published data only}
    1. Imai Y, Kawata S, Tamura S, Ito N, Seki K, Nishiuchi M, et al. Recombinant interferon‐α‐2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study. Liver 1997;17:88‐92. - PubMed
Iyoda 2000 {published data only}
    1. Iyoda K, Yuki N, Kato M, Sugiyasu Y, Komori M, Fujii E, et al. Retreatment with interferon for chronic hepatitis C after transient response. Journal of Clinical Gastroenterology 2000;31(4):297‐301. - PubMed
Jensen 2009 {published data only}
    1. Jensen DM, Marcellin P, Frelich B, Andreone P, Bisceglie A, Brando CE, et al. Re‐treatment of patients with chronic hepatitis C who do not respond to peginterferon α2b. A randomized trial. Annals of Internal Medicine 2009;150(8):528‐40. - PubMed
Kakumu 1994 {published data only}
    1. Kakumu S, Yoshioka K. Retreatment with interferon in patients with chronic hepatitis C. Journal of Hepatology 1994;21(3):483. - PubMed
Katayama 2001 {published data only}
    1. Katayama K, Kasahara A, Sasaki Y, Kashiwagi T, Naito M, Masuzawa M, et al. Immunological response to interferon‐gamma priming prior to interferon‐alpha treatment in refractory chronic hepatitis C in relation to viral clearance. Journal of Viral Hepatitis 2001;8(3):180‐5. - PubMed
Kishihara 1995 {published data only}
    1. Kishihara Y, Hayashi J, Ohmiya M, Nakashima K, Ikematsu H, Kashiwagi S. A preliminary study of retreatment of chronic hepatitis C with interferon. Fukuoka Igaku Zasshi 1995;86(4):113‐20. - PubMed
Kumar 2001 {published data only}
    1. Kumar KS, Brown M. Daily vs. thrice weekly interferon in combination with ribavirin for patients with chronic hepatitis C infection: preliminary results of a multicenter randomized trial. Gastroenterology 2001;120(5):A571.
Le 1996 {published data only}
    1. Le X, Zhou X, Dai X. Evaluation of interferon (alpha)‐2b for the treatment of relapsed hepatitis C. Hepatology 1996;24(4 Pt 2):536A.
Leroy 2001 {published data only}
    1. Leroy V, Dutertre N, Tran A, Naveau S, Abergel A, Bronwicki JP, et al. High‐daily induction dose of interferon in combination with ribavirin in chronic hepatitis C non responder patients: a randomised controlled trial. Journal of Hepatology 2001;34(1):146.
Lindsay 1996 {published data only}
    1. Lindsay KL, Davis GL, Schiff ER, Bodenheimer HC, Balart LA, Dienstag JL, et al. Response to higher doses of interferon alfa‐2b in patients with chronic hepatitis C: a randomized multicenter trial. Hepatitis Interventional Therapy Group. Hepatology 1996;24(5):1034‐40. [MEDLINE: ] - PubMed
Lodato 2005 {published data only}
    1. Lodato F, Azzaroli F, Brillanti S, Colecchia A, Tame MR, Montagnani M, et al. Higher doses if peginterferon alpha‐2b administered twice weekly improve sustained virological response in difficult‐to‐treat patients with chronic hepatitis C: results of a pilot randomized study. Journal of Viral Hepatitis 2005;12:536‐42. - PubMed
Mangia 2005 {published data only}
    1. Mangia A, Cimino L, Persico M, Dernelia M, Rumi M, Spinzi O, et al. Enhanced response to peginterferon alfa‐2a‐based triple therapy in previously non‐responsive chronic hepatitis C: final results of PRETTY study. Journal of Hepatology 2005;42 Suppl 2:200‐1.
Mangia 2008 {published data only}
    1. Mangia A, Minerva N, Bacca D, Cozzolongo R, Ricci GL, Carretta V, et al. Individualized treatment duration for hepatitis C genotype 1 patients: a randomized controlled trial. Hepatology 2008;47(1):43‐50. - PubMed
Marcellin 1994 {published data only}
    1. Marcellin P, Boyer N, Pouteau M, Benhamou JP, Erlinger S. Retreatment with interferon‐alpha of chronic hepatitis C virus infection. Lancet 1994;344(8923):690‐1. - PubMed
Marco 2000 {published data only}
    1. Marco VD, Almasio P, Vaccaro A, Ferraro D, Parisi P, Cataldo MG. 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(3):456‐62. - PubMed
Marriott 1992 {published data only}
    1. Marriott E, Quiroga JA, Carreno V. Retreatment of chronic hepatitis C with interferon‐alpha. Journal of Infectious Diseases 1992;166(5):1200‐1. - PubMed
Mathew 2006 {published data only}
    1. Mathew A, Peiffer LP, Rhoades K, McGarrity T. Sustained viral response to pegylated interferon alpha‐2b and ribavirin in chronic hepatitis C refractory to prior treatment. Digestive Diseases and Sciciences 2006;51:1956‐61. - PubMed
    1. Mathew A, Peiffer LP, Rhoades K, McGarrity TJ. Improvement in quality of life measures in patients with refractory hepatitis C, responding to retreatment with pegylated interferon alfa‐2b and ribavirin. Health and Quality of Life Outcomes 2006;4(30):1‐8. - PMC - PubMed
Milella 1999 {published data only}
    1. 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(2):211‐5. - PubMed
Min 2001 {published data only}
    1. Min AD, Jones JL, Esposito S, Lebovics E, Jacobson IM, Klion FM, et al. Efficacy of high‐dose interferon in combination with ribavirin in patients with chronic hepatitis C resistant to interferon alone. American Journal of Gastroenterology 2001;96(4):1143‐9. - PubMed
Moreno‐Otero 2003 {published data only}
    1. Moreno‐Otero R. Controlled study of interferon alpha‐2b plus ribavirin in patients with chronic hepatitis C non‐responders to interferon. Journal of Hepatology 2003;38 Suppl 2:158.
    1. Moreno‐Otero R. Prospective, randomized and controlled study of the efficacy and tolerance of interferon alpha plus ribavirin in chronic hepatitis C non responders to prior interferon. Hepatology 2001;34(4):596A.
Mura 1999 {published data only}
    1. Mura D, Deliperi R, Fastame L, Cugia L, Cossu PA, Pisanu G. Interferon therapy of HCV cirrhosis reduces the incidence of HCC, and decompensation, and significantly improves survival: a 5 year comparative trial. Hepatology 1999;29:A1251.
Neuman Manuela 2010 {published data only}
    1. Neuman Manuela G, Katz Gadi G, Patel A, Izabell M, Izabella Malkiewicz M, Esguerra R. HCV‐RNA and inflammasome is modulated by PEGylated interferon (PEG‐IFNalpha‐2b) monotherapy in chronic hepatitis C patients. Clinical Biochemistry. 2010; Vol. Meeting of the Canadian Society of Clinical Chemists, CSCC 2010 Saskatoon, SK Canada.June 13‐16, 2010.
Nevens 2005 {published data only}
    1. Nevens F, Vlierberghe V, D'heygere F, Delwaide J, Adler M, Henrion J, et al. Peginterferon alfa‐2a (40 kDa) plus ribavirin is as effective in patients relapsing after conventional interferon based therapy as in naive patients: results from the BERNAR‐1 trial. Journal of Hepatology 2005;42 Suppl 2:214.
Nishiguchi 1995 {published data only}
    1. Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, et al. Randomised trial of effects of interferon‐alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 1995;346(8982):1051‐5. - PubMed
    1. Nishiguchi S, Kuroki T, Nakatani S, Takeda T, Fukuda K, Tamori A, et al. Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis. Lancet 2001;357:196‐7. - PubMed
Nomura 2004 {published data only}
    1. Nomura H, Sou S, Nagahama T, Hayashi J, Kashiwagi S, Ishibashi H. Efficacy of early retreatment with interferon β for relapse in patients with genotype 1b chronic hepatitis C. Hepatology Research 2004;28:36‐40. - PubMed
Pardo 1994 {published data only}
    1. Pardo M, Cotonat T, Herrero M, Marriott E, Artillo S, Quiroga JA, et al. Retreatment of chronic hepatitis C virus infection (Letter). Lancet 1994;343(8912):1568‐9. - PubMed
Payen 1998 {published data only}
    1. Payen JL, Izopet I, Galindo V, Zarski JP, Seigneurin JM, Dussaix E, et al. A comparison of three interferon alpha‐2b regimens for retreatment (RTT) of patients with chronic hepatitis C with prior complete response followed by relapse: a controlled, randomized trial (AASLD abstract). Hepatology 1996;24(4 Pt 2):273A.
    1. Payen JL, Izopet J, Galindo‐Migeot V, Lauwers‐Cances V, Zarski JP, Seigneurin JM, et al. Better efficacy of a 12‐month interferon alfa‐2b retreatment in patients with chronic hepatitis C relapsing after a 6‐month treatment: a multicenter, controlled, randomized trial. Le Groupe D'etude et De Traitement du Virus De L'hepatite C (Get.Vhc). Hepatology 1998;28(6):1680‐6. [MEDLINE: ] - PubMed
Perasso 1999 {published data only}
    1. Perasso A, Testino G, Ansaldi F, Venturino V, Icardi GC. Recombinant interferon alfa‐2b/ribavirin combined therapy followed by low dose recombinant interferon alfa‐2b in chronic hepatitis C interferon nonresponders. Hepatology 1999;29(1):297‐8. - PubMed
Picciotto 1997 {published data only}
    1. Picciotto A, Sinelli N, Brizzolara R, Campo N, Lapertosa G, Celle G. Long‐term interferon alfa‐2b retreatment of relapsing patients with chronic hepatitis C. Journal of Hepatology 1997;26(2):447‐8. - PubMed
Planas 2002 {published data only}
    1. Planas R, Quer JC, Enriquez J, Barrera JM, Dalmau B, Casanovas T, et al. Induction therapy with interferon alfa‐2a in compensated hepatitis C virus‐related cirrhosis. Randomized, multicenter study [Terapia de induccion con interferon alfa‐2a en la cirrosis por el virus de la hepatitis C compensada. Estudio multicentrico aleatorizado]. Medicina Clinica 2002;118(17):641‐4. - PubMed
Pockros 2007 {published data only}
    1. Goodman ZD, Becker RL, Pockros PJ, Afdhal NH. Progression of fibrosis in advanced chronic hepatitis C: evaluation by morphometric image analysis. Hepatology 2007;45(4):886‐94. - PubMed
Pol 1999 {published data only}
    1. Pol S, Couzigou P, Bourliere 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. - PubMed
Portal 2003 {published data only}
    1. Portal I, Botta‐Fridlund D, Bourliere M, Rotily M, Halfon P, Couzigou P, et al. Treatment with peg‐interferon alfa‐2b in relapsers to standard interferon plus ribavirin in chronic hepatitis C: efficacy and safety results from a randomized multicentric french study. Hepatology 2003;38(4):311A.
Poynard 1999 {published data only}
    1. Poynard T, Daurat V, Chevret S, Moussalli J, Degos F, Bailly F, et al. A short induction regimen of interferon‐alpha is not effective for treatment of relapse in chronic hepatitis C: a randomized trial. For the multicentre GER‐CYT‐01 group. Journal of Viral Hepatitis 1999;6(5):381‐6. [MEDLINE: ] - PubMed
Poynard 2003 {published data only}
    1. Poynard T, Marcellin P, Bissery A, Myers P, Moussalli J, Degos F, et al. Reinforced interferon alpha‐2b and ribavirin is more effective than standard combination therapy in he retreatment of chronic hepatitis C previously nonresponsive to interferon: a randomized trial. Journal of Viral Hepatitis 2003;10:197‐204. - PubMed
Puoti 2001 {published data only}
    1. Puoti M, Cadeo GP, Forleo M.A, Barni M.C, Cristini G, Rossi S, et al. Pilot dose‐finding trial on interferon alpha in combination with ribavirin for the treatment of chronic hepatitis C in patients not responding to interferon alone. Digestive and Liver Disease 2001;33:163‐72. - PubMed
Qu 2012 {published data only}
    1. Qu L‐S, Chen H, Kuai X‐L, Xu Z‐F, Jin F, Zhou G‐X. Effects of interferon therapy on development of hepatocellular carcinoma in patients with hepatitis C‐related cirrhosis: A meta‐analysis of randomized controlled trials. Hepatology Research 2012;42(8):782‐9. - PubMed
Reichard 1994 {published data only}
    1. Reichard O, Glaumann H, Weiland O. Long‐term histological outcome in patients with chronic hepatitis C treated repeatedly with interferon alpha‐2b without sustained response. Scandinavian Journal of Infectious Diseases 1994;26(4):383‐9. - PubMed
Rodriguez‐Torres 2011 {published data only}
    1. Rodriguez‐Torres M, Hillson JL, Bacon BR, Box TD, Hassanein T, Greenbloom S, et al. Safety and efficacy of pegylated interferon lambda (PEG‐LAMBDA) compared to pegylated interferon alfa‐2A (PEG‐alfa) in HCV‐infected patients (G1/2/3) with compensated cirrhosis: emerge phase IIB efficacy and safety results through week 12. Hepatology 2011;54(4 Suppl):994A‐6A.
Rolachon 1997 {published data only}
    1. Rolachon A, Kezachian G, Causse X, Baud M, Fournet J, Zarski JP. Interest of high dose of interferon in non‐responder CHC patients. Journal of Hepatology 1996;25 Suppl 1:S149.
    1. Rolachon A, Kezachian G, Causse X, Baud M, Leroy V, Maynard‐Muet M, et al. Value of high‐dose interferon‐alpha in chronic viral hepatitis C patients non‐responder to a 1st treatment. Pilot study prospective and randomized trial. Gastroenterologie Clinique et Biologique 1997;21(12):924‐8. [MEDLINE: ] - PubMed
Romero‐Gomez 2012 {published data only}
    1. Romero‐Gomez M, Planas R, Sola R, Garcia‐Samaniego J, Diago M, Crespo J, et al. Peginterferon alpha‐2A achieves higher early virological responses (RVR and CEVR) than peginterferon alpha‐2B in chronic Hepatitis C: Meta‐analysis of randomized clinical trials (RCT). Journal of Hepatology 2012;56 Suppl 2:S456.
Rustgi 2005 {published data only}
    1. Rustgi V, Nelson D, Balan V, Sulkowski M, Lambiase L, Davis G, et al. Phase 2 dose‐escalation study of albuferon combined with ribavirin in non‐responders to prior interferon‐based therapy for chronic hepatitis C infection. Journal of Hepatology 2005;44 Suppl 2:S50.
Salmeron 1999 {published data only}
    1. 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. - PubMed
Saracco 1994 {published data only}
    1. Saracco G, Rosina F, Abate ML, Carucci P, Solinas A, Chiandussi L, et al. Long‐term response to interferon‐alfa 2b re‐treatment in chronic hepatitis C. Journal of Hepatology 1994;21(2):278‐9. - PubMed
Saracco 2001 {published data only}
    1. Saracco G, Ciancio A, Olivero A, Smedile A, Roffi L, Croce G, et al. A randomized 4‐arm multicenter study of interferon alfa‐2b plus ribavirin in the treatment of patients with chronic hepatitis C not responding to interferon alone. Hepatology 2001;34(1):133‐8. - PubMed
Saracco 2002 {published data only}
    1. Saracco G, Olivero A, Ciancio A, Carenzi S, Smedile A, Cariti G, et al. A randomized 4‐arm multicenter study of interferon alfa‐2b plus ribavirin in the treatment of patients with chronic hepatitis C relapsing after interferon monotherapy. Hepatology 2002;36(4):955‐66. - PubMed
Sarrazin 2007 {published data only}
    1. Sarrazin C, Rouzier R, Wagner F, Forestier N, Larrey D, Gupta SK, et al. SCH 503034, a novel hepatitis C virus protease inhibitors, plus pegilated interferon alfa‐2b for genotype 1 nonresponders. Gastroenterology 2007;132:1270‐8. - PubMed
Scotto 1996 {published data only}
    1. 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. - PubMed
Scotto 1998 {published data only}
    1. Scotto G, Grimaldi M. Effectiveness of Leukocyte Interferon‐alfa treatment in patients with chronic hepatitis C not responsive to recombinant Interferon. Digestive Diseases and Sciences 1998;43(10):2173‐6. - PubMed
Shiffman 2000 {published data only}
    1. Shiffman ML, Hofmann CM, Gabbay J, Luketic VA, Sterling RK, Sanyal AJ. Treatment of chronic hepatitis C in patients who failed interferon monotherapy: effects of higher doses of interferon and ribavirin combination therapy. The Virginia Cooperative Hepatitis Treatment Group. American Journal of Gastroenterology 2000;95(10):2928‐35. - PubMed
Singal 2010 {published data only}
    1. Singal AG, Waljee AK, Shiffman M, Bacon BR, Schoenfeld PS. Meta‐analysis: re‐treatment of genotype I hepatitis C nonresponders and relapsers after failing interferon and ribavirin combination therapy. Alimentary Pharmacology and Therapeutics 2010;32:969‐83. - PubMed
Soza 2005 {published data only}
    1. Soza A, Heller T, Ghany M, Lutchman G, Liang TJ, Germain J, et al. Pilot study of interferon gamma for chronic hepatitis C. Journal of Hepatology 2005;43:67‐71. - PubMed
Sporea 2006 {published data only}
    1. Sporea I, Danila M, Sirli R, Popescu A, Laza A, Baditoiu L. Comparative study concerning the efficacy of peg‐IFN alfa‐2a versus peg‐IFN alfa‐2b on the early virological response in patients with chronic viral C hepatitis. Journal of Gastrointestinal and Liver Diseases 2006;15(2):125‐30. - PubMed
Steindl‐Munda 2003 {published data only}
    1. Steindl‐Munda P, Ferenci P, Brunner H, Nachbaur K, Datz C, Gschwantler M, et al. Impact of high‐dose interferon induction and ribavirin therapy in patients with chronic hepatitis C relapsing after or not responding to interferon monotherapy. Liver International 2003;23:269‐75. - PubMed
Suzuki 2001 {published data only}
    1. Suzuki F, Chayama K, Tsubota A, Akuta N, Someya T, Kobayashi M, et al. Twice‐daily administration of interferon‐beta for chronic hepatitis C is not superior to once‐daily regimen. Journal of Gastroenterology 2001;36(4):242‐7. - PubMed
Tassopoulos 2003 {published data only}
    1. Raptopoulou M, Tsantoulas D, Vafiadi I, Ketikoglou I, Paraskevas E, Vassiliadis T, et al. The effect of adherence to therapy on sustained response in daily or three times a week interferon alpha‐2b plus ribavirin treatment of naïve and nonresponder chronic hepatitis C patients. Journal of Viral Hepatitis 2005;12:91‐5. - PubMed
    1. Tassopoulos NC, Tsantoulas D, Raptopoulou M, Vassiliadis T, Kanatakis S, Paraskevas E, et al. A randomized trial to assess the efficacy of interferon alpha in combination with ribavirin in the treatment of interferon alpha nonresponders with chronic hepatitis C: superior efficacy of high daily dosage of interferon alpha in genotype 1. Journal of Viral Hepatitis 2003;10:189‐96. - PubMed
Toyota 2002 {published data only}
    1. Iino S, Tomita E, Kumada H, Suzuki H, Toyota J, Kendo K, et al. Prediction of treatment outcome with daily high‐dose interferon alfa‐2b plus ribavirin in patients with chronic hepatitis C with genotype 1b and high HCV RNA levels: relationship of baseline viral levels and viral dynamics during and after therapy. Hepatology Research 2004;30:63‐70. - PubMed
    1. Toyoda J, Sainokami S, Yasuda K, Izumi N, Ota H, Sato Y, et al. Comparision of interferon alfa‐2b and ribavirin (SCH18908) combination therapy and interferon alfa‐2b monotherapy in chronic hepatitis C patients who have not responded or relapsed to previous interferon therapy: a double‐blind comparative study to examine concomitant efficacy. Journal of Clinical and Therapeutical Medicine 2002;4:539‐63.
Valla 1999 {published data only}
    1. Valla DC, Chevallier M, Marcellin P, Payen JL, Trepo C, Fonck M, et al. Treatment of hepatitis C virus‐related cirrhosis: a randomized, controlled trial of interferon alfa‐2b versus no treatment. Hepatology 1999;29(6):1870‐5. - PubMed
Wartelle 1997 {published data only}
    1. Wartelle CF, Larson AM, Cotler SJ, Gretch DR. Higher dose interferon does not increase end‐of‐treatment virological response in nonresponders to interferon therapy (AASLD abstract). Hepatology 1997;4(Pt 2):415A.
Weiland 1993 {published data only}
    1. Weiland O, Zhang YY, Widell A. Serum HCV RNA levels in patients with chronic hepatitis C given a second course of interferon alpha‐2b treatment after relapse following initial treatment. Scandinavian Journal of Infectious Diseases 1993;25(1):25‐30. - PubMed
Yao 1997 {published data only}
    1. Yao GB, Fu XX, Xu DZ, Hao LI, Su CX, Huangpu YS. A randomized, comparative, multicenter study of consensus interferon (CIFN) with interferon alpha‐2a in patients with chronic hepatitis C virus (HCV) infection (Abstract). Hepatology 1997;26(4S):1174.
Zeuzem 2000 {published data only}
    1. Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai MY, Gane E, et al. Peginterferon alfa‐2a in patients with chronic hepatitis C. New England Journal of Medicine 2000;343(23):1666‐72. - PubMed
Zeuzem 2005 {published data only}
    1. Zeuzem S, Pawlotsky J‐M, Lukasiewicz, Wagner M, Goulis I, Lurie Y, et al. International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C. Journal of Hepatology 2005;43:250‐7. - PubMed

References to studies awaiting assessment

Cho 1992 {published data only}
    1. Cho HJ, Dong SH, Lee MS, Kim HY, Park CK, Yoo JY, et al. Interferon alpha therapy in patients with chronic type C hepatitis: changes of serum ALT, anti‐HCV, & HCV‐RNA. Korean Journal of Internal Medicine 1992;7(1):13‐7. - PMC - PubMed
Testino 2002 {published data only}
    1. Testino G. Hepatocarcinoma in HCV compensated correlated liver cirrhosis: role of treatment with interferon. Recenti Progressi in Medicina 2002;93:302‐7. - PubMed

Additional references

Arase 2007
    1. Arase Y, Ikeda K, Suzuki F, Suzuki Y, Kobayashi M, Akuta N, et al. Interferon‐induced prolonged biochemical response reduces hepatocarcinogenesis in hepatitis C virus infection. Journal of Medical Virology 2007;79(10):1485‐90. - PubMed
Barrett 2001
    1. Barrett S, Goh J, Coughlan B, Ryan E, Stewart S, O'Keane JC, et al. The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection. Gut 2001;49:423‐30. - PMC - PubMed
Benvegnu 2004
    1. Benvegnu L, Gios M, Boccato S, Alberti A. Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications. Gut 2004;53(5):744‐9. - PMC - PubMed
Brok 2005a
    1. Brok J, Gluud LL, Gluud C. Ribavirin monotherapy for chronic hepatitis C. Cochrane Database of Systematic Reviews 2005, Issue 4. [DOI: 10.1002/14651858.CD005527] - DOI - PubMed
Brok 2005b
    1. Brok J, Gluud LL, Gluud C. Ribavirin plus interferon versus interferon for chronic hepatitis C. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD005445] - DOI - PubMed
Brok 2008
    1. 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;61:763‐9. - PubMed
Brok 2009
    1. 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. - PubMed
Camma 1999
    1. Camma C, Giunta M, Chemello L, Alberti A, Toyoda H, Trepo C, et al. Chronic hepatitis C: interferon retreatment of relapsers. A meta‐analysis of individual patient data. European Concerted Action on Viral Hepatitis (EUROHEP). Hepatology 1999;30(3):801‐7. - PubMed
Camma 2001
    1. Camma C, Giunta M, Andreone P, Craxi A. Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence‐based approach. Journal of Hepatology 2001;34(4):593‐602. - PubMed
Casaraghi 2004
    1. Casiraghi MA, Paschale M, Romano L, Biffi R, Assi A, Binelli G, et al. Long‐term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth. Hepatology 2004;39:90‐6. - PubMed
Chavilitdhamrong 2006
    1. Chavalitdhamrong D, Tanwandee T. Long‐term outcomes of chronic hepatitis C patients with sustained virological response at 6 months after the end of treatment. World Journal of Gastroenterology 2006;12:5532‐5. - PMC - PubMed
Cheng 2001
    1. Cheng SJ, Bonis PA, Lau J, Pham NQ, Wong JB. Interferon and ribavirin for patients with chronic hepatitis C who did not respond to previous interferon therapy: a meta‐analysis of controlled and uncontrolled trials. Hepatology 2001;33(1):231‐40. - PubMed
Ciancio 2006
    1. Ciancio A, Smedile A, Giordanino C, Colletta C, Croce G, Pozzi M, et al. Long‐term follow‐up of previous hepatitis C virus positive nonresponders to interferon monotherapy successfully retreated with combination therapy: are they really cured?. American Journal of Gastroenterology 2006;101:1811‐6. - PubMed
CTU 2011
    1. Copenhagen Trial Unit. TSA ‐ Trial Sequential Analysis. http://ctu.dk/tsa/ (accessed 29 September 2012).
Davis 1989
    1. 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
DeMets 1987
    1. DeMets DL. Methods of combining randomized clinical trials: strengths and limitations. Statistics in Medicine 1987;6:341‐8. - PubMed
DerSimonian 1986
    1. DerSimonian R, Laird N. Meta‐analysis in clinical trials. Controlled Clinical Trials 1986;7(3):177‐88. - PubMed
Egger 1997
    1. Egger M, Smith GD, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ (Clinical Research Ed.) 1997;315(7109):629‐34. - PMC - PubMed
Everson 2008
    1. Everson GT, Balart L, Lee SS, Reindollar RW, Shiffman ML, Minuk GY, et al. Histological benefits of virological response to peginterferon alfa‐2a monotherapy in patients with hepatitis C and advanced fibrosis or compensated cirrhosis. Alimentary Pharmacology & Therapeutics 2008;27:542‐51. - PubMed
Fattovich 1997
    1. Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow‐up study of 384 patients. Gastroenterology 1997;112(2):463‐72. - PubMed
Fried 2002
    1. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. Peginterferon alfa‐2a plus ribavirin for chronic hepatitis C virus infection. New England Journal of Medicine 2002;347(13):975‐82. - PubMed
Gluud 2007
    1. Gluud C, Brok J, Gong Y, Koretz RL. Hepatology may have problems with putative surrogate outcome measures. Journal of Hepatology 2007;46:734‐42. - PubMed
Gluud 2012
    1. 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)). 2012, Issue 5. Art. No.: LIVER.
Higgins 2002
    1. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Statistics in Medicine 2002;21(11):1539‐58. - PubMed
Higgins 2011
    1. 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.
Hoofnagle 2002
    1. Hoofnagle JH. Course and outcome of Hepatitic C. Hepatology 2002;36(5 Suppl1):S21‐S29. - PubMed
Hung 2006
    1. Hung CH, Lee CM, Lu SN, Wang JH, Hu TH, Tung HD, et al. Long‐term effect of interferon alpha‐2b plus ribavirin therapy on incidence of hepatocellular carcinoma inpatients with hepatitis C virus‐related cirrhosis. Journal of Viral Hepatitis 2006;13:409‐14. - PubMed
ICH‐GCP 1997
    1. 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 practice1997 CFR & ICH Guidelines. Vol. 1, PA 19063‐2043, USA: Barnett International/PAREXEL, 1997. [MEDLINE: ]
Innes 2011
    1. Innes HA, Hutchinson SJ, Allen S, Bhattacharyya D, Bramley P, Delahooke TES, et al. Excess liver‐related morbidity of chronic hepatitis C patients, who achieve a sustained viral response, and are discharged from care. Hepatology 2011;54:1547‐58. - PubMed
Jacobson 2011
    1. Jacobson IM, McHutchison JG, Dusheiko G, 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
Kenny‐Walsh 1999
    1. Kenny‐Walsh E, for the Irish Hepatology Research Group. Clinical outcomes after hepatitis C infection from contaminated anti‐D immune globulin. New England Journal of Medicine 1999;340:1228‐33. - PubMed
Kjaergard 2001
    1. Kjaergard LL, Villumsen J, Gluud C. Reported methodological quality and discrepancies between small and large randomized trials in meta‐analyses. Annals of Internal Medicine 2001;135(11):982‐9. - PubMed
Koretz 1995
    1. Koretz RL. Chronic hepatitis: more quotes and misquotes. In: Gitnick G editor(s). Current Hepatology. Vol. 15, St. Louis: Mosby‐Year Book, Inc., 1995:49‐84.
Koretz 1996
    1. Koretz RL. Interferon and hepatocellular carcinoma. Lancet 1996;347:194. - PubMed
Lauer 2001
    1. Lauer GM, Walker BD. Hepatitis C virus infection. New England Journal of Medicine 2001;345(1):41‐52. - PubMed
Lindsay 2001
    1. Lindsay KL, Trepo C, Heintges T, Shiffman ML, Gordon SC, Hoefs JC, et al. A randomized, double‐blind trial comparing pegylated interferon alfa‐2b to interferon alfa‐2b as initial treatment for chronic hepatitis C. Hepatology 2001;34(2):395‐403. - PubMed
Maddrey 1999
    1. Maddrey WC. Safety of combination interferon alfa‐2b/ribavirin therapy in chronic hepatitis C‐relapsed and treatment‐naive patients. Seminars in Liver Disease 1999;19 Suppl 1:67‐75. - PubMed
Manns 2001
    1. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa‐2b plus ribavirin compared with interferon alfa‐2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358(9286):958‐65. - PubMed
Marcellin 1997
    1. Marcellin P, Boyer N, Gervais A, Martinot M, Pouteau M, Castelnau C, et al. Long‐term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon‐alpha therapy. Annals of Internal Medicine 1997;127(10):875‐81. - PubMed
Maylin 2008
    1. Maylin S, Martinot‐Peignoux M, Moucari R, Boyer N, Ripault MP, Cazals‐Hatem D, et al. Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C. Gastroenterology 2008;135(3):821‐9. - PubMed
McHutchison 1998
    1. 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
McHutchison 2002
    1. McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C, et al. Adherence to combination therapy enhances sustained response in genotype‐1‐infected patients with chronic hepatitis C. Gastroenterology 2002;123(4):1061‐9. - PubMed
Moher 1998
    1. 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. - PubMed
Newell 1992
    1. Newell DJ. Intention‐to‐treat analysis: implications for quantitative and qualitative research. International Journal of Epidemiology 1992;21(5):837‐41. - PubMed
NIH 1997
    1. Anonymous. Management of Hepatitis C. NIH Consensus Statement 1997;15(3):1‐41. - PubMed
Papatheodoridis 2001
    1. Papatheodoridis GV, Papadimitropoulos VC, Hadziyannis SJ. Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis: a meta‐analysis. Alimentary Pharmacology & Therapeutics 2001;15(5):689‐98. - PubMed
Perz 2006
    1. Perz JF, Armstrong GL, Farrington LA, Hutin YL, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. Journal of Hepatology 2006;45(4):529‐38. - PubMed
Poordad 2011
    1. 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. - PMC - PubMed
Poynard 1998
    1. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Gaetano I, et al. Randomised trial of interferon alfa‐2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alfa‐2b 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
Poynard 2003a
    1. Poynard T, Yuen MF, Ratziu V, Lai CL. Viral hepatitis C. Lancet 2003;362(9401):2095‐100. - PubMed
Poynard 2009
    1. Poynard T, Munteanu M, Colombo M, Bruix J, Schiff E, Terg R, et al. Impact of PegIntron maintenance therapy on biomarkers (Fibro Test[FT]‐ActiTest[AT]) in cirrhotic (METAVIOR F4) HCV prior nonresponders: results from the EPIC3 cirrhosis maintenance trial. Hepatology 2009;50(4 Suppl):711A.
RevMan 2011 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
Royle 2003
    1. Royle P, Milne R. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591‐603. - PubMed
Schulz 1995
    1. Schulz 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(5):408‐12. - PubMed
Seeff 1999
    1. Seeff LB, Miller RN, Rabin CS, Buskell‐Bales Z, Straley‐Eason KD, Smoak BL, et al. 45‐year follow‐up of hepatitis C virus infection in healthy young adults. . Annals of Internal Medicine 1999;132:105‐11. - PubMed
Seeff 2001
    1. Seeff LB, Hollinger FB, Alter HJ, Wright EC, Cain CM, Buskell ZJ, et al. Long‐term mortality and morbidity of transfusion‐associated non‐A, non‐B and type C hepatitis: a National Heart, Lung, and Blood Institute Collaborative Study. Hepatology 2001;33:455‐63. - PubMed
Thorlund 2009
    1. 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. - PubMed
Thorlund 2010
    1. 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. - PMC - PubMed
Thorlund 2011
    1. Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C. User manual forTrial Sequential Analysis (TSA). http://ctu.dk/tsa/files/tsa_manual.pdf 2011 (accessed 15 June 2012).
Vogt 1999
    1. Vogt M, Lang T, Frosner G, Klingler C, Sendl AF, Zeller A, et al. Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood‐donor screening. New England Journal of Medicine 1999;341:866‐70. - PubMed
Wetterslev 2008
    1. 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;61:64‐75. - PubMed
Wetterslev 2009
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in a random‐effects meta‐analysis. BMC Medical Research Methodology 2009;9:86. - PMC - PubMed
Wiese 2000
    1. Wiese M, Berr F, Lafrenz M, Porst H, Oesen U. Low frequency of cirrhosis in a hepatitis C (genotype 1b) single‐source outbreak in Germany: a 20‐year multicenter study. Hepatology 2000;32:91‐6. - PubMed
Wood 2008
    1. Wood L, Egger M, Gluud LL, Schulz KF, Juni 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. [PUBMED: 18316340] - PMC - PubMed
Wright 2002
    1. Wright TL. Treatment of patients with hepatitis C and cirrhosis. Hepatology 2002;36(5 Suppl 1):S185‐94. - PubMed

References to other published versions of this review

Myers 2002
    1. Myers RP, Poynard T. Interferon for interferon nonresponding and relapsing patients with chronic hepatitis C. Cochrane Database of Systematic Reviews 2002, Issue 4. [DOI: 10.1002/14651858.CD003617] - DOI - PubMed

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