Intervention Review

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Antiviral interventions for liver transplant patients with recurrent graft infection due to hepatitis C virus

  1. Kurinchi Selvan Gurusamy1,*,
  2. Emmanuel Tsochatzis2,
  3. Clare D Toon3,
  4. Elias Xirouchakis4,
  5. Andrew K Burroughs5,
  6. Brian R Davidson1

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 4 DEC 2013

Assessed as up-to-date: 14 FEB 2013

DOI: 10.1002/14651858.CD006803.pub4


How to Cite

Gurusamy KS, Tsochatzis E, Toon CD, Xirouchakis E, Burroughs AK, Davidson BR. Antiviral interventions for liver transplant patients with recurrent graft infection due to hepatitis C virus. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD006803. DOI: 10.1002/14651858.CD006803.pub4.

Author Information

  1. 1

    Royal Free Campus, UCL Medical School, Department of Surgery, London, UK

  2. 2

    Royal Free Hampstead NHS Foundation Trust and UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, London, UK

  3. 3

    University College London, Division of Surgery & Interventional Science, London, London, UK

  4. 4

    Athens Medical Group, Hospital P. Faliro, GI and Hepatology, Athens, Greece

  5. 5

    Royal Free Hampstead NHS Foundation Trust, Sheila Sherlock Liver Centre, London, UK

*Kurinchi Selvan Gurusamy, Department of Surgery, Royal Free Campus, UCL Medical School, Royal Free Hospital, Rowland Hill Street, London, NW3 2PF, UK. k.gurusamy@ucl.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 4 DEC 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Aguilera 2011

MethodsRandomised clinical trial.


ParticipantsCountry: Spain.
Number randomised: 68.
Post-randomisation drop-outs: Not stated.
Revised sample size: 68.
Mean age: Not stated.
Females: Not stated.
Interval between liver transplantation and start of intervention/control: Not stated.

Inclusion criteria:

  1. Established recurrent HCV disease evaluated by a liver biopsy.


Exclusion criteria:

  1. HIV seropositivity.
  2. HBV coinfection.
  3. Contraindications for antiviral therapy.
  4. Rejection in the baseline biopsy.


InterventionsParticipants were randomly assigned to 1 of 2 groups.
Group 1: Peg interferon - alpha 2a (n = 34).

Further details: Not available.

Genotype 1: Not stated.

Group 2: Peg interferon - alpha 2b (n = 34).
Further details of control: Not available.
Genotype 1: Not stated.


OutcomesNone of the outcomes of interest for this review were reported in this trial.


NotesAttempts were made to contact the authors in March 2013. No replies were received.

Consent for donation: Not stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?Unclear riskComment: This information was not available.

Angelico 2007

MethodsRandomised clinical trial.


ParticipantsCountry: Italy.
Number randomised: 42.
Post-randomisation drop-out: 0.
Revised sample size: 42.

Mean age: 57 years.
Females: 14 (33.3%).
Interval between liver transplantation and start of intervention/control: 48 months for ribavirin plus peg interferon vs. 40 months per interferon.

Inclusion criteria:

  1. OLT with recurrent HCV.
  2. Non-cirrhotic.
  3. Age ≤ 70 years.
  4. Liver transplantation due to HCV-related cirrhosis performed at least 1 year earlier.
  5. Detectable serum HCV-RNA.
  6. Persistently abnormal ALT serum levels.
  7. Histological evidence of established HCV hepatitis in the graft.


Exclusion criteria:

  1. Previous antiviral treatment after liver transplantation.
  2. Baseline counts of leukocytes < 3000 cells/mm3; platelets < 70,000 cells/mm3; Hb value < 12 g/dL.
  3. Serum creatinine > 2 mg/dL at least twice in the last 6 months.
  4. Active alcohol or drugs, or both,consumption.
  5. HIV virus or HBV co-infections.
  6. Renal or thyroid dysfunctions.
  7. History of autoimmune hepatitis, haematological or psychiatric diseases.
  8. Significant cardiovascular abnormalities.
  9. Neoplastic diseases.
  10. Clinically significant bleeding disorders.
  11. Other organ transplantation.
  12. Pregnancy or lactation.
  13. Active steroid treatment.


InterventionsParticipants were randomly assigned to 1 of 2 groups.

Group 1: Ribavirin plus peg interferon (n = 21).
Further details: Ribavirin: 200 mg/day to maximum tolerated dose; interferon 180 μg/weekly for 48 weeks.
Genotype 1: 18 (85.7%).

Group 2: Peg interferon (n = 21).

Further details: Peg interferon: 180 μg/weekly for 48 weeks.
Genotype 1: 17 (81%).


OutcomesThe outcomes reported were mortality, graft rejection, serious adverse events, and fibrosis response.


NotesAttempts were made to contact the authors in December 2007. Authors provided additional information. Further attempts were made to contact the authors in February 2013. No replies were received.

Consent for donation: Not stated. Ethical approval for research was obtained.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Using a computerized random list blinded to clinical investigators" (author replies).

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Important outcomes such as retransplantation were not reported.

Free from source of funding bias?High riskQuote: "They received partial funding from Roche s.p.a., Milan, Italy which enabled them to carry out their research."

Belli 2012

MethodsRandomised clinical trial


ParticipantsCountry: Multicentre (Europe).

Number randomised: 73.

Post-randomisation drop-outs: 1 (1.4%).

Revised sample size: 72.

Mean age: 54 years.

Females: 8 (11.1%).

Interval between liver transplantation and start of intervention/control: Not stated.

Inclusion criteria:

  1. Adult first liver transplant participants (> 18 years of age).
  2. Had mild–moderate histological recurrent hepatitis C.


Exclusion criteria:
1. Signs of cholestatic hepatitis (defined by a total bilirubin > 3 mg/dL).
2. Ishak staging score higher than 3 at the time of the 1 year protocol liver biopsy.
3. Previous organ transplantation.
4. Co-infection with hepatitis or HIV.
5. Ongoing biliary tract disease at the time of randomisation.
6. Major vascular problems portal vein or hepatic artery thrombosis.
7. Renal failure defined by serum creatinine > 2 mg/dL.
8. Contraindications to interferon and ribavirin therapy.


InterventionsParticipants were randomly assigned to 1 of 2 groups.
Group 1: Peg interferon alpha 2b (n = 36).
Further details: Treated participants received escalating doses of peg interferon alpha 2b starting from 0.5-1 µg/kg once weekly, up to 1.5 µg/kg within 2-4 weeks if tolerated together with escalating doses of ribavirin starting from 400-600 mg once daily, up to a maximal tolerated dose of 14 mg/kg/day for 52 weeks.

Genotype 1: Not stated.
Group 2: Control (n = 36).
Further details: No intervention.

Genotype 1: Not stated.


OutcomesThe outcomes reported were rejection and fibrosis worsening.


NotesAttempts were made to contact the authors in March 2013. No replies were received.
Reasons for post-randomisation drop-outs: Did not receive allocated intervention.

Consent for donation: Not stated. Ethical approval for research was obtained.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was centralized and performed by an independent unit according to a randomization list prepared by a biostatistician."

Allocation concealment (selection bias)Low riskQuote: "Randomization was centralized and performed by an independent unit according to a randomization list prepared by a biostatistician."

Blinding (performance bias and detection bias)
All outcomes
High riskQuote: "The design of this multicentre, randomized, controlled, open label study was developed …"

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?High riskQuote: "Drug supply was provided by Schering-Plough. A financial support from Schering-Plough was given to the Co-ordinating Center and it was utilized for independent monitoring, centralized revision liver biopsies and statistical analysis."

Calmus 2012

MethodsRandomised clinical trial.


ParticipantsCountry: France.

Number randomised: 78.

Post-randomisation drop-outs: 1 (1.3%).

Revised sample size: 77.

Mean age: 53 years.

Females: 21 (27.3%).

Interval between liver transplantation and start of intervention/control: 2.6 years (no data available for each group separately).

Inclusion criteria:

  1. Adult (age 18-70 years) first-time liver transplantation recipients.
  2. Recurrent HCV and fibrosis PF1 (METAVIR) at liver biopsy obtained 1-5 years after liver transplantation.
  3. HBsAg-negative liver disease.
  4. Detectable serum HCV RNA by PCR.
  5. Must have been taking calcineurin inhibitors (cyclosporine or tacrolimus) with a stable immunosuppressive regimen for at least 6 months.


Exclusion criteria:

  1. Previous treatment with interferon alpha after transplantation.
  2. Retransplantation.
  3. Associated organ transplantation.
  4. Recurrent hepatocellular carcinoma after liver transplantation.
  5. Serum HIV positivity.
  6. Acute rejection episode within the past 6 months or histological features compatible with acute or rejection at screening biopsy (ie, acute rejection, loss of > 25% of interlobular bile ducts, centrilobular ischaemia).
  7. Fibrosing cholestatic hepatitis.
  8. Unresolved biliary complications.
  9. Serum creatinine level > 200 µmol/L.
  10. GGT level > 20 x ULN.
  11. Bilirubin level > 100 µmol/L.
  12. Neutrophil count < 1500/mm3.
  13. Platelet count < 50,000/mm3.
  14. Hb level < 10 g/dL (women) or < 11 g/dL (men). 


InterventionsParticipants were randomly assigned to 1 of 2 groups.
Group 1: Ribavirin (n = 40).
Further details: Ribavirin: 1000 mg or function of haematological tolerance for a period of 12 months.

Genotype 1: 31 (77.5%).
Group 2: Control (n = 37).
Further details: Placebo.
Genotype 1: 30 (81.1%).

Other details:

Both groups received 12 months of combination therapy with peg interferon alpha 2a plus ribavirin prior to randomisation.


OutcomesThe outcomes reported were mortality, retransplantation, and serious adverse events.


NotesAttempts were made to contact the authors in March 2013. Authors provided additional information.

Reasons for post-randomisation drop-outs: Adverse event.

Consent for donation: Not stated. Ethical approval for research was obtained.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was performed on a central basis, with local balance, by questioning an internet site."

Allocation concealment (selection bias)Low riskQuote: "Randomization was performed on a central basis, with local balance, by questioning an internet site."

Blinding (performance bias and detection bias)
All outcomes
Low riskComment: Blinding was achieved by the use of placebo.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)Low riskComment: Important outcomes such as mortality and retransplantation were reported.

Free from source of funding bias?High riskQuote: "This work was supported by a grant from the French National Direction for Clinical Research (Direction de la Recherche Clinique) and by Roche Pharma France."

Carrion 2007

MethodsRandomised clinical trial.


ParticipantsCountry: Spain.
Number randomised: 54.
Post-randomisation drop-out: 0.
Revised sample size: 54.

Mean age: 60 years.
Females: 20 (37%).
Interval between liver transplantation and start of intervention/control: 15 months for peg interferon plus ribavirin vs. 17 months for control.

Inclusion criteria:

  1. Mild hepatitis C recurrence (fibrosis stage F0 to F2).
  2. At least 6 months after liver transplantation.
  3. 18-70 years of age.


Exclusion criteria:

  1. HIV or HBV infection.
  2. Previous organ transplantation.
  3. Renal failure.
  4. Contraindications to interferon and ribavirin treatment.


InterventionsParticipants were randomly assigned to 1 of 2 groups.

Group 1: Peg interferon plus ribavirin (n = 27).
Further details: Peg interferon: 1.5 μg/kg/weekly sc; ribavirin: 400-1200 mg/day for 48 weeks.
Genotype 1: 23 (85.2%).

Group 2: Control (n = 27).

Further details: No intervention.
Genotype 1: 23 (85.2%).


OutcomesThe outcomes reported were mortality, graft rejection, and fibrosis response.


NotesAttempts were made to contact the authors in March 2009. No replies were received.

Consent for donation: Not stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Allocation of participants was based on computer-generated random numbers."

Allocation concealment (selection bias)Unclear riskQuote: "Allocation concealment was performed with sealed envelopes."

Comment: Further details were not available.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?High riskQuote: "Supported in part by grants from Instituto de Salud Carlos III (PI 05/1285, FIS 05/0258). José A. Carrión received a grant from Hospital Clínic (Premi Fi de Residència)."

Chalasani 2005

MethodsRandomised clinical trial


ParticipantsCountry: USA.
Number randomised: 67.
Post-randomisation drop-out: 2 (3%).
Revised sample size: 65.

Mean age: 52 years.
Females: 10 (15.4%).
Interval between liver transplantation and start of intervention/control: 26 months for peg interferon vs. 23 months for control.

Inclusion criteria:

  1. HCV infected liver transplant recipients.
  2. 6 months after liver transplantation.
  3. ALT > 1.5 times before randomisation.
  4. Histological evidence of hepatitis.
  5. No histological evidence of rejection at 8 weeks before randomisation.


Exclusion criteria:

  1. Prior interferon therapy.
  2. Neutrophil 1500/μL; Hb < 10 g/dL.
  3. Creatinine > 2.0 mg/dL.
  4. Cirrhosis.
  5. Cholestatic fibrosing hepatitis.
  6. Uncontrolled epilepsy.
  7. Alcohol or drug abuse within 1 year of entry.
  8. Severe psychiatric illness.
  9. Immune disorder.
  10. COPD.
  11. Cardiac disease.
  12. Poorly controlled thyroid disease.


InterventionsParticipants were randomly assigned to 1 of 2 groups.

Group 1: Peg interferon (n = 33).
Further details: Peg interferon: 180 μg/weekly sc for 48 weeks.
Genotype 1: 26 (78.8%).

Group 2: Control (n = 32).

Further details: No intervention.
Genotype 1: 24 (75%).


OutcomesThe outcomes reported were mortality, serious adverse events, graft rejection, and fibrosis response.


NotesAttempts were made to contact the authors in December 2007 and March 2013. Authors provided additional information.

Reason for post-randomisation drop-outs: 1 did not receive study drug; 1 no investigation beyond baseline investigation.

Consent for donation: Not stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Central randomization generated by the computer" (author replies).

Allocation concealment (selection bias)Low riskQuote: "Held by third party" (author replies).

Blinding (performance bias and detection bias)
All outcomes
High riskComment: It was an open-label study so participants and study personnel were not blinded (author replies). 

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Post-randomisation drop-outs could be related to the outcomes.

Selective reporting (reporting bias)High riskComment: Important outcomes such as retransplantation were not reported.

Free from source of funding bias?High riskQuote: "Supported by a grant from Roche Laboratories Inc., Nutley, NJ."

Cotler 2001

MethodsRandomised clinical trial.


ParticipantsCountry: USA.
Number randomised: 12.
Post-randomisation drop-out: Not stated.
Revised sample size: 12.

Mean age: 54 years.
Females: 2 (16.7%).
Interval between liver transplantation and start of intervention/control: 34 months for interferon vs. 11 months for control.

Inclusion criteria:

  1. Adult OLT.
  2. > 7 months post transplant.
  3. Anti-HCV seropositive.
  4. Persistently detectable HCV RNA in serum after OLT.
  5. HCV hepatitis.


Exclusion criteria:

  1. Cirrhosis.
  2. Rejection on histology.


InterventionsParticipants were randomly assigned to 1 of 2groups.

Group 1: Interferon (n = 8).
Further details: Interferon: 3 million units/day for 52 weeks.
Genotype 1: 6 (75%).

Group 2: Control (n = 4).

Further details: no intervention.
Genotype 1: 4 (100%).


OutcomesThe outcomes reported were mortality, retransplantation, and graft rejection.


NotesAttempts were made to contact the authors in December 2007. Authors provided additional information. Further attempts were made to contact the authors in March 2013. No replies were received.

Consent for donation: Not stated. Ethical approval for research was obtained.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was achieved by a computer generated random number table" (author replies).

Allocation concealment (selection bias)Low riskQuote: "Held by a third party" (author replies).

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)Low riskComment: Important outcomes such as mortality and retransplantation were reported.

Free from source of funding bias?High riskQuote: "Supported by Roche Laboratories, Inc. and the Byron Koch Memorial Fund."

Crippin 1996

MethodsRandomised clinical trial.


ParticipantsCountry: USA.
Number randomised: 35.
Post-randomisation drop-out: 8 (22.9%).
Revised sample size: 27.

Average age: Not stated.
Females: Not stated.
Interval between liver transplantation and start of intervention/control: Not stated.

Inclusion criteria:

  1. > 3 months post liver transplant.
  2. Histological hepatitis.
  3. ALT more than 2 times normal.
  4. Seropositivity for HCV-RNA.


InterventionsParticipants were randomly assigned to 1 of 4 groups.

Group 1: Interferon 1 million units (n = 6).

Genotype 1: Not stated.
Group 2: Interferon 3 million units (n = 9).

Genotype 1: Not stated.

Group 3: Interferon 6 million units (n = 6).

Genotype 1: Not stated.

Group 4: Control (n = 6).

Further details: No intervention.

Genotype 1: Not stated.


OutcomesNone of the outcomes of interest for this review were reported.


NotesAttempts were made to contact the authors in December 2007 and March 2013. Authors provided additional information.

Reason for post-randomisation drop-outs: Not stated.

Consent for donation: Not stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Random number table" (author replies).

Allocation concealment (selection bias)Unclear riskQuote: "Sealed envelope" (author replies).

Blinding (performance bias and detection bias)
All outcomes
High riskQuote: "Study was not blinded" (author replies).

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Post-randomisation drop-outs could be related to the outcomes.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?Unclear riskComment: This information was not available.

Gane 1998

MethodsRandomised clinical trial.


ParticipantsCountry: UK.
Number randomised: 30.
Post-randomisation drop-out: 2 (6.7%).
Revised sample size: 28.

Mean age: 54 years.
Females: 7 (25%).
Interval between liver transplantation and start of intervention/ control: 7 months for ribavirin vs. 6 months for interferon.

Inclusion criteria:

  1. Adults.
  2. Surviving at 6 months after OLT-related HCV cirrhosis.
  3. Serological evidence of recurrent HCV infection.
  4. Serum AST > normal range.
  5. Chronic hepatitis without evidence of rejection.


Exclusion criteria:

  1. Previous episode of steroid-resistant acute rejection.
  2. Chronic rejection.
  3. Pregnant women.
  4. Unreliable contraception.
  5. WBC < 1500 cells per μl; platelet < 50,000 cells per μl; Hb < 10 g/dL.


InterventionsParticipants were randomly assigned to 1 of 2 groups.

Group 1: Ribavirin (n = 16).
Further details: Ribavirin: 500-600 mg twice daily oral for 24 weeks.
Genotype 1: 8 (57.1%).

Group 2: Interferon (n = 14).

Further details: Interferon: 3 million units three times weekly sc for 24 weeks.
Genotype 1: 6 (42.9%).


OutcomesThe outcomes reported were mortality and fibrosis response.


NotesAttempts were made to contact the authors in December 2007. No replies were received.

Reason for post-randomisation drop-outs: 2 participants who developed adverse effects from ribavirin group were excluded from analysis.

Consent for donation: Not stated. Ethical approval for research was obtained.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Post-randomisation drop-outs were related to the outcomes.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?Unclear riskComment: This information was not available.

Gane 2009

MethodsRandomised clinical trial.


ParticipantsCountry: Australia and New Zealand.

Number randomised: 56.

Post-randomisation drop-outs: Not stated.

Revised sample size: 56.

Mean age: Not stated.

Females: Not stated.

Interval between liver transplantation and start of intervention/control: At least 6 months after liver transplantation (no further details available).

Inclusion criteria:

  1. Subjects with compensated recurrent hepatitis C after liver transplantation.


InterventionsParticipants were randomly assigned to 1 of 2 groups.
Group 1: Peg interferon-alpha 2a plus ribavirin (n = 28).
Further details: Peg interferon-alpha 2a 180 µg/week plus ribavirin 400 mg twice daily for 48 weeks.

Genotype 1: Not stated.
Group 2: Peginterferon-alpha 2a (n = 28).
Further details: Peginterferon-alpha 2a monotherapy for 48 weeks.

Genotype 1: Not stated.


OutcomesThe outcomes reported were mortality, serious adverse events, and graft rejection.


NotesAttempts were made to contact the authors in March 2013. No replies were received.

Consent for donation: Not stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Important outcomes such as retransplantation were not reported.

Free from source of funding bias?Unclear riskComment: This information was not available.

Ghalib 2000

MethodsRandomised clinical trial.


ParticipantsCountry: USA.
Number randomised: 5.
Post-randomisation drop-out: Not stated.
Revised sample size: 5.

Mean age: Not stated.
Females: Not stated.
Interval between liver transplantation and start of intervention/control: Not stated.

Inclusion criteria:

  1. Adult participants with HCV recurrence after liver transplantation.


InterventionsParticipants were randomly assigned to 1 of 2 groups.

Group 1: Interferon plus ribavirin (n = 3).
Further details: Interferon: 6 million units sc three times weekly; ribavirin: 800 mg/day for 24 weeks.
Genotype 1: Not stated.

Group 2: Interferon plus ribavirin (n = 2).

Further details: Interferon: 6 million units sc thrice weekly; ribavirin: 800 mg/day for 48 weeks.
Genotype 1: Not stated.


OutcomesNone of the outcomes of interest for this review were reported in this trial.


NotesAttempts were made to contact the authors in December 2007. No replies were received.

Consent for donation: Not stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?Unclear riskComment: This information was not available.

Ghalib 2006

MethodsRandomised clinical trial.


ParticipantsCountry: USA.
Number randomised: 59.
Post-randomisation drop-out: 0.
Revised sample size: 59.

Mean age: 51 years.
Females: 20 (33.9%).
Interval between liver transplantation and start of intervention/control: Not stated.

Inclusion criteria:

  1. OLT participants with histological recurrent HCV.


InterventionsParticipants were randomly assigned to 1 of 2 groups.

Group 1: Peg interferon (high dose) plus ribavirin (n = 32).
Further details: Interferon: started at 0.5 μg/day for 4 weeks followed by 1.5 μg/day for 48 weeks; ribavirin: 600 mg/day increased to 800 mg/day at 4 weeks.
Genotype 1: Not stated individually.

Group 2: Peg interferon (low dose) plus ribavirin (n = 27).

Further details: Interferon: started at 0.5 μg/day for 52 weeks; ribavirin: 600 mg/day increased to 800 mg/day at 4 weeks.
Genotype 1: Not stated individually.

Genotype 1 in both groups: 43/59 (72.9%).


OutcomesNone of the outcomes of interest for this review were reported in this review.


NotesAttempts were made to contact the authors in December 2007. Authors provided additional information. Further attempts were made to contact the authors in March 2013. No replies were received.

Consent for donation: Not stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was by random number table; stratified on genotype and fibrosis stage" (author replies).

Allocation concealment (selection bias)Low riskQuote: "The random number table was held by the project manager for the study" (author replies).

Blinding (performance bias and detection bias)
All outcomes
High riskQuote: "Once the dose was determined for a subject, there was no blinding on dosing of the peginterferon alfa-2b" (author replies).

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?Unclear riskComment: This information was not available.

Gordon 2005

MethodsRandomised clinical trial.


ParticipantsCountry: USA.
Number randomised: 13.
Post-randomisation drop-out: 0.
Revised sample size: 13.

Mean age: Not stated.
Females: Not stated.
Interval between liver transplantation and start of intervention/control: 44 months after transplantation (individual groups not stated).

Inclusion criteria:

  1. Recurrent HCV after liver transplantation.


InterventionsParticipants were randomly assigned to 1 of 2 groups.

Group 1: Peg interferon (high dose) plus ribavirin (n = 9).
Further details: interferon: 1.5 μg/kg/weekly sc; ribavirin 200 mg twice daily increased to 400 mg twice daily for 52 weeks.
Genotype 1: 7 (77.8%).

Group 2: Peg interferon (low dose) plus ribavirin (n = 4).

Further details: interferon: 0.5 μg/kg/weekly sc; ribavirin 200 mg twice daily increased to 400 mg twice daily for 52 weeks.
Genotype 1: 2 (50%).


OutcomesThe outcome reported was graft rejection.


NotesAttempts were made to contact the authors in December 2007. Authors provided additional information. Further attempts were made to contact the authors in March 2013. No replies were received.

Consent for donation: Not stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The envelopes were sealed and mixed by a third party, numbered sequentially from 1-21, and then opened in sequence at each randomization" (author replies).

Allocation concealment (selection bias)Low riskQuote: "The envelopes were sealed and mixed by a third party, numbered sequentially from 1-21, and then opened in sequence at each randomization" (author replies).

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?Unclear riskComment: This information was not available.

Lodato 2008

MethodsRandomised clinical trial.


ParticipantsCountry: Italy.
Number randomised: 18.
Post-randomisation drop-out: 0.
Revised sample size: 18.

Mean age: Not stated.
Females: Not stated.
Interval between liver transplantation and start of intervention/control: Not stated.

Inclusion criteria:

  1. Liver transplantation for HCV-related cirrhosis.
  2. Failure to achieve virological response (detectable HCV RNA or < 2 log drop in the HCV RNA level) at week 24 with peg interferon 1 μg/kg weekly plus ribavirin 8-10 mg/kg/day.
  3. Detectable HCV-RNA by PCR.
  4. HCV genotype-1 infection.
  5. Elevated serum ALT levels and histological features of HCV hepatitis in the graft on liver biopsy.


Exclusion criteria:

  1. Evidence of decompensated liver disease.
  2. Histological evidence of rejection and drug-related injury.
  3. HBsAg positivity.
  4. HIV positivity.
  5. Moderate to severe anaemia (Hb < 10 g/dL).
  6. Leukopenia (WBC < 1500 µL).
  7. Thrombocytopenia (< 50,000 platelets/μL blood).
  8. Impaired renal function (creatinine clearance < 50 mL/minute).
  9. Significant history of cardiovascular and psychiatric diseases and ongoing alcohol abuse and previous post-liver transplantation treatment with peg interferon.


InterventionsParticipants were randomly assigned to 1 of 2 groups.

Group 1: Peg interferon plus ribavirin (n = 9).
Further details: Interferon: 1 μg/kg weekly; ribavirin 8-10 mg/kg/day for 24 more weeks.
Genotype 1: 9 (100%).

Group 2: Control (n = 9).

Further details: No intervention.
Genotype 1: 9 (100%).


OutcomesNone of the outcomes of interest for this review were reported in this trial.


NotesAttempts were made to contact the authors in April 2009. Authors provided additional information. Further attempts were made to contact the authors in March 2013. No replies were received.

Consent for donation: Not stated. Ethical approval for research was obtained.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The random sequence was generated by means of random number table" (author replies).

Allocation concealment (selection bias)Unclear riskQuote: "The allocation was concealed by means of sealed envelopes" (author replies).

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?High riskQuote: "F. Lodato received research funding from Roche S.p.A. M. Biselli and S. Lorenzini received research funding from Associazione per la Ricerca sulle Malattie Epatiche (ARME), Bologna, Italy."

Nair 2008

MethodsRandomised clinical trial.


ParticipantsCountry: USA.
Number randomised: 50.
Post-randomisation drop-out: 20 (40%).
Revised sample size: 30.

Mean age: 53 years.
Females: 8 (23.3%).
Interval between liver transplantation and start of intervention/control: 6 months for amantadine plus peg interferon plus ribavirin vs. 6 months for peg interferon plus ribavirin.

Inclusion criteria:

  1. Positive HCV RNA level by PCR.
  2. Elevated ALT.
  3. A liver biopsy consistent with recurrent HCV in the absence of acute or chronic rejection.


Exclusion criteria:

  1. Any cause for active chronic liver disease other than chronic hepatitis C.
  2. Evidence of poor graft function or transplant-related complications such as ascites, high serum bilirubin more than 5 mg/dL, untreated biliary complications such as intrahepatic strictures.
  3. Any pre-existing medical conditions that could interfere with the treatment, such as uncontrolled seizure disorders, ischaemic heart disease, or severe malnutrition.
  4. Pre-existing psychiatric conditions; especially depression, a history of severe psychiatric disorder, such as major psychoses, suicidal ideation, or suicidal attempt.
  5. Pre-existing anaemia Hb < 12 g/dL for women or < 13 g/dL for men.
  6. Absolute neutrophil count < 1500/mm3.
  7. Platelets < 50,000/mm3.
  8. Serum albumin < 3.0 g/dL.
  9. Serum creatinine > 1.4 mg/dL.


InterventionsParticipants were randomly assigned to 1 of 2 groups.

Group 1: Amantadine plus peg interferon plus ribavirin (n = 13).
Further details: Amantadine: 200 mg/day; interferon: 1.0 μg/kg/week; ribavirin: 800 mg/day for 52 weeks.
Genotype 1: Not stated.

Group 2: Peg interferon plus ribavirin (n = 17).

Further details: Interferon: 1.0 μg/kg/week; ribavirin: 800 mg/day for 52 weeks.
Genotype 1: Not stated.


OutcomesThe outcome reported was fibrosis worsening.


NotesAttempts were made to contact the authors in March 2009. No replies were received.

Reason for post-randomisation drop-outs: 5 participants who did not receive the drugs because of lack of insurance or because of psychosocial reasons and 15 who developed adverse effects were excluded from analysis.

Consent for donation: Not stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskQuote: "Randomization was done using sealed envelopes with the seal broken only after the patient signed the consent."

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Post-randomisation drop-outs could be related to the outcomes.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?Unclear riskComment: This information was not available.

Samuel 2003

MethodsRandomised clinical trial.


ParticipantsCountry: France.
Number randomised: 52.
Post-randomisation drop-out: 0.
Revised sample size: 52.

Mean age: 57 years.
Females: 16 (30.8%).
Interval between liver transplantation and start of intervention/control: 54 months for interferon plus ribavirin vs. 57 months for control.

Inclusion criteria:

  1. Adult first-time liver transplant recipients.
  2. Recurrence of hepatitis C in the graft (> 6 months after transplant).
  3. Histopathologically confirmed chronic hepatitis (METAVIR score ≥ 1; Fibrosis score ≥ F0 on liver.
  4. 18-70 years of age.
  5. Taking cyclosporine or tacrolimus.


Exclusion criteria:

  1. Previous treatment with interferon after transplantation.
  2. Retransplantation for rejection or chronic hepatitis C on the graft.
  3. Associated hepatocellular carcinoma ≥ 3 cm at histological evaluation after transplantation.
  4. Serum HBsAg positivity.
  5. Serum HIV positivity.
  6. Acute rejection episode within the past 6 months or histological features of rejection on screening biopsy.
  7. Unresolved biliary complications.
  8. Serum creatinine level > 200 μmol/L.
  9. GGT level > 20 x ULN.
  10. Bilirubin level ≥ 100 μmol/L.
  11. Neutrophil count < 1500/mm3; platelet count < 50,000/mm3, Hb level < 10 g/dL for women or < 11 g/dL for men.
  12. Associated other organ or bone marrow transplantation.
  13. Hepatic arterial thrombosis.


InterventionsParticipants were randomly assigned to 1 of 2 groups.

Group 1: Interferon plus ribavirin (n = 28).
Further details: Interferon: 3 million units three times weekly sc; ribavirin: 400-600 mg twice daily orally for 48 weeks
Genotype 1: 23 (82.1%).

Group 2: Control (n = 24).

Further details: No intervention.

Genotype 1: 20 (83.3%).


OutcomesThe outcomes reported was mortality, graft rejection, and fibrosis worsening.


NotesAttempts were made to contact the authors in December 2007. Authors provided additional information. Further attempts were made to contact the authors in March 2013. No replies were received.

Consent for donation: Not stated. Ethical approval for research was obtained.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The randomisation was computer generated, by envelope and organized by Schering Plough" (author replies).

Allocation concealment (selection bias)Low riskQuote: "The randomisation was computer generated, by envelope and organized by Schering Plough" (author replies).

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Important outcomes such as retransplantation were not reported.

Free from source of funding bias?High riskQuote: "The randomisation was computer generated, by envelope and organized by Shering Plough."

Yedibela 2011

MethodsRandomised clinical trial.


ParticipantsCountry: Germany.

Number randomised: 24.

Post-randomisation drop-outs: 3 (12.5%).

Revised sample size: 21.

Mean age: 52 years.

Females: 6 (28.6%).

Interval between liver transplantation and start of intervention/control: Not stated.

Inclusion criteria:

  1. Participants with recurrent HCV after liver transplantation who did not respond or relapsed after initial treatment with interferon (3-6 million IU three times weekly) plus ribavirin (800-1200 mg/day) for at least 12 months.  


InterventionsParticipants were randomly assigned to 1 of 2 groups.
Group 1: Peg interferon plus ribavirin (n = 10).
Further details: Peg interferon 0.8 µg/kg/week plus ribavirin (800-1200 mg/day) for 6 months.

Genotype 1: 10 (100%).
Group 2: Peg interferon (n = 11).
Further details: Peg interferon monotherapy 0.8 µg/kg/week for 6 months.

Genotype 1: 11 (100%).
Both groups received 12 months of combination therapy with peg interferon plus ribavirin prior to randomisation


OutcomesNone of the outcomes of interest for this review were reported in this trial.


NotesAttempts were made to contact the authors in February 2013. No replies were received.
Reasons for post-randomisation drop-outs: not completed 6 months of treatment (undergoing treatment).

Consent for donation: Not stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and retransplantation were not reported.

Free from source of funding bias?Unclear riskComment: This information was not available.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Beckebaum 2003Not a randomised clinical trial.

Beckebaum 2004Not a randomised clinical trial.

Boillot 1995Not a randomised clinical trial.

Casanovas 2004Comment on an included trial.

Castedal 2003Not a randomised clinical trial.

Catalano 2003Not a randomised clinical trial.

Ceccherini 2003Not a randomised clinical trial.

Crippin 2002Efficacy of treatment before liver transplantation.

Dumortier 2002Not a randomised clinical trial.

Duvoux 2006Details on controls not available.

Fontana 2007Not a randomised clinical trial.

Israeli 2001Not a randomised clinical trial.

Kizilisik 1997Not a randomised clinical trial.

Pinna 2001Not a randomised clinical trial.

Samuel 2002Review of treatment.

Samuel 2004Outcomes of interest not reported.

Samuel 2005Editorial on an included trial.

Samuel 2007Editorial on an included trial.

Shakil 1999Outcomes of interest not reported.

Shakil 2004Outcomes of interest not reported.

Taltavull 2004Comment on an included trial.

Targhetta 2001Not a randomised clinical trial.

Testino 2006Not a randomised clinical trial.

Vargas 1995Not a randomised clinical trial.

Wietzke 2000Not a randomised clinical trial.

 
Comparison 1. Intervention versus control

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality8Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Peg interferon versus no intervention control
165Risk Ratio (M-H, Fixed, 95% CI)0.48 [0.05, 5.09]

    1.2 Peg interferon plus ribavirin versus no intervention control
154Risk Ratio (M-H, Fixed, 95% CI)3.0 [0.13, 70.53]

    1.3 Ribavirin plus peg interferon versus peg interferon
298Risk Ratio (M-H, Fixed, 95% CI)0.5 [0.05, 5.20]

    1.4 Interferon versus no intervention control
112Risk Ratio (M-H, Fixed, 95% CI)1.67 [0.08, 33.75]

    1.5 Interferon plus ribavirin versus no intervention control
152Risk Ratio (M-H, Fixed, 95% CI)0.29 [0.01, 6.74]

    1.6 Ribavirin versus interferon
130Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.7 Ribavirin versus placebo
177Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Retransplantation after start of therapy2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Interferon versus no intervention control
112Risk Ratio (M-H, Fixed, 95% CI)1.67 [0.08, 33.75]

    2.2 Ribavirin versus placebo
177Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Treatment-related serious adverse events (proportion)2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 Ribavirin plus peg interferon versus peg interferon
156Risk Ratio (M-H, Fixed, 95% CI)3.4 [1.46, 7.94]

    3.2 Ribavirin versus placebo
177Risk Ratio (M-H, Fixed, 95% CI)5.55 [0.70, 43.95]

 4 Treatment-related serious adverse events (number of serious adverse events)2Rate Ratio (Fixed, 95% CI)Subtotals only

    4.1 Peg interferon versus no intervention control
165Rate Ratio (Fixed, 95% CI)1.15 [0.52, 2.57]

    4.2 Ribavirin plus peg interferon versus peg interferon
142Rate Ratio (Fixed, 95% CI)1.20 [0.36, 3.96]

 5 Graft rejection requiring retransplantation after start of therapy2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    5.1 Peg interferon plus ribavirin versus no intervention control
172Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.07, 15.38]

    5.2 Interferon versus no intervention control
112Risk Ratio (M-H, Fixed, 95% CI)1.67 [0.08, 33.75]

 6 Graft rejection requiring medical treatment1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    6.1 Ribavirin plus peg interferon versus peg interferon
142Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.04, 2.95]

 7 Graft rejection (others with unknown treatment)5Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    7.1 Peg interferon versus no intervention control
165Risk Ratio (M-H, Fixed, 95% CI)24.26 [1.50, 393.41]

    7.2 Peg interferon plus ribavirin versus no intervention control
154Risk Ratio (M-H, Fixed, 95% CI)3.0 [0.13, 70.53]

    7.3 Ribavirin plus peg interferon versus peg interferon
156Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.07, 15.21]

    7.4 Peg interferon (1.5 μg/kg/week) plus ribavirin versus peg interferon (0.5 μg/kg/week) plus ribavirin
113Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.5 Interferon plus ribavirin versus no intervention control
152Risk Ratio (M-H, Fixed, 95% CI)2.59 [0.11, 60.69]

 8 Fibrosis worsening7Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    8.1 Peg interferon versus no intervention control
145Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.30, 2.19]

    8.2 Peg interferon plus ribavirin versus no intervention control
2126Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.51, 0.98]

    8.3 Ribavirin plus peg interferon versus peg interferon
142Risk Ratio (M-H, Fixed, 95% CI)2.0 [0.20, 20.41]

    8.4 Amantadine plus peg interferon plus ribavirin versus peg interferon plus ribavirin
130Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.28, 2.02]

    8.5 Interferon plus ribavirin versus no intervention control
152Risk Ratio (M-H, Fixed, 95% CI)0.29 [0.01, 6.74]

    8.6 Ribavirin versus interferon
130Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.28, 1.88]

 
Summary of findings for the main comparison. Antiviral therapy for recurrent liver graft infection with hepatitis C virus (mortality)

Mortality

Patient or population: Participants with recurrent liver graft infection with hepatitis C virus.
Settings: Secondary or tertiary setting.
Intervention: Various interventions.
Comparison: Various controls.

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlIntervention

Peg interferon vs.control62 per 100030 per 1000
(3 to 318)
RR 0.48
(0.05 to 5.09)
65
(1 study)
⊕⊝⊝⊝
very low1,2
The assumed risk was the control group risk.

Peg interferon plus ribavirin vs.control63 per 1000189 per 1000
(8 to 1000)
RR 3
(0.13 to 70.53)
54
(1 study)
⊕⊝⊝⊝
very low1,2
Since there were no deaths in the control group, the assumed risk was the control group risk in a different trial included in this review.

Ribavirin plus peg interferon vs.peg interferon41 per 100020 per 1000
(2 to 212)
RR 0.5
(0.05 to 5.2)
98
(2 studies)
⊕⊝⊝⊝
very low1,2
The assumed risk was the control group risk.

Interferon vs.control63 per 1000105 per 1000
(5 to 1000)
RR 1.67
(0.08 to 33.75)
12
(1 study)
⊕⊝⊝⊝
very low1,2
Since there were no deaths in the control group, the assumed risk was the control group risk in a different trial included in this review.

Interferon plus ribavirin vs.control42 per 100012 per 1000
(0 to 281)
RR 0.29
(0.01 to 6.74)
52
(1 study)
⊕⊝⊝⊝
very low1,2
The assumed risk was the control group risk.

Ribavirin vs.interferonThere were no deaths in either group.Not estimable30
(1 study)
⊕⊝⊝⊝
very low1,2
-






Ribavirin vs.placeboThere were no deaths in either group.Not estimable77
(1 study)
⊕⊝⊝⊝
very low1,2
-






*The basis for the assumed risk is provided in the comments section. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; peg: pegylated; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 The trial(s) was (were) of high risk of bias.
2 The confidence intervals overlapped 1 and either 0.75 or 1.25 or both. The number of events in the intervention and control group was fewer than 300.
 
Summary of findings 2. Antiviral therapy for recurrent liver graft infection with hepatitis C virus (retransplantation)

Retransplantation

Patient or population: Participants with recurrent liver graft infection with hepatitis C virus.
Settings: Secondary or tertiary setting.
Intervention: Various interventions.
Comparison: Various controls.

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlIntervention

Retransplantation after start of therapy - ribavirin vs.placeboNo retransplantation in either groupNot estimable77
(1 study)
⊕⊝⊝⊝
very low1,2






Retransplantation after start of therapy - interferon vs.control10 per 100017 per 1000
(1 to 338)
RR 1.67
(0.08 to 33.75)
12
(1 study)
⊕⊝⊝⊝
very low1,2
There was no retransplantation in the control group. So, we used an assumed risk of 1%.

*The basis for the assumed risk is provided in the comments section. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 The trial(s) was (were) of high risk of bias.
2 The confidence intervals overlapped 1 and either 0.75 or 1.25 or both. The number of events in the intervention and control group was fewer than 300.