Antiviral prophylactic intervention for chronic hepatitis C virus in patients undergoing liver transplantation

Kurinchi Selvan Gurusamy; Emmanuel Tsochatzis; Brian R Davidson; Andrew K Burroughs

doi:10.1002/14651858.CD006573.pub2

Antiviral prophylactic intervention for chronic hepatitis C virus in patients undergoing liver transplantation

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Referencias

References to studies included in this review

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estudios excluidos
otras referencias

Belli LS, Alberti AB, Rondinara GF, de CL, Corti A, Mazza E, et al. Early ribavirin treatment and avoidance of corticosteroids in hepatitis C virus (HCV)‐positive liver transplant recipients: Interim report of a prospective randomized trial. Transplantation Proceedings2001; Vol. 33, issue 1‐2:1353‐4.

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

Belli 2001

Methods	Randomised clinical trial
Participants	Country: Italy. Sample size: 19. Post‐randomisation drop‐out: unclear. Revised sample size: 19. Females: not stated. Mean age: not stated. Genotype 1 (intervention): not stated. Genotype 1 (control): not stated. Growth factors for bone marrow suppression: no. Inclusion criteria: Liver transplantation for HCV infection Exclusion criteria: Early transplant deaths.
Interventions	The participants were randomly assigned to two groups. Group 1: ribavirin (n = 11). Further details: 400 to 600 mg per day orally. Group 2: control (n = 8). Timing of commencement of treatment: as soon as patients could tolerate food.
Outcomes	The outcomes reported were inflammatory activity and adverse effects of drug.
Notes	Reasons for post‐randomisation drop‐out: Initially 37 patients were randomised to three groups. Only two groups were included for this review. A total of 7 patients died in all the three groups. It is not clear how many died in each group. Hence, these data could not be used in our review.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	High risk
Incomplete outcome data addressed? All outcomes	High risk	Comment: Post‐randomisation drop‐outs could be related to the outcomes.
Free of selective reporting?	High risk	Comment: Important primary outcomes were not reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.

Chalasani 2005

Methods	Randomised clinical trial
Participants	Country: USA. Sample size: 54. Post‐randomisation drop‐out: 0 (0%). Revised sample size: 54. Females: 11 (20.4%). Mean age: 52.6 years. Genotype 1 (intervention): 19 (73.1%). Genotype 1 (control): 21 (75%). Growth factors for bone marrow suppression: no. Inclusion criteria: 1. HCV infected liver transplant recipients. 2. ALT > 1.5 times before liver transplantation. 3. No histological evidence of rejection at 3 weeks after transplantation. Exclusion criteria: 1. Prior interferon therapy. 2. Neutrophil 1500/μL; Hb < 10gm/dl. 3. Creatinine > 2.0mg/ 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.
Interventions	The participants were randomly assigned to two groups. Group 1: peg interferon alpha 2a (n = 26). Further details: 180 mcg/weekly sc for 48 weeks. Group 2: control (n = 28). Timing of commencement of treatment: 3 weeks after liver transplantation.
Outcomes	The outcomes reported were virological response, histological response, and adverse effects.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	High risk
Incomplete outcome data addressed? All outcomes	High risk	Comment: Fibrosis and activity scores reported only in 12 and 11 patients in the intervention and control groups respectively.
Free of selective reporting?	High risk	Comment: Important primary outcomes were not reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.
Free from source of funding bias?	High risk	Quote: 'Supported by a grant from Roche Laboratories Inc., Nutley, NJ'

Charlton 2007

Methods	Randomised clinical trial
Participants	Country: USA. Sample size: 115. Post‐randomisation drop‐out: 13 (11.3%). Revised sample size: 102. Females: not stated. Mean age: not stated. Genotype 1 (intervention): not stated. Genotype 1 (control): not stated. Growth factors for bone marrow suppression: no. Inclusion criteria: 1. Patients undergoing liver transplantation for HCV infection. 2. Before histologically apparent recurrence of HCV.
Interventions	The participants were randomly assigned to two groups. Group 1: peg interferon alpha 2a and ribavirin (n = 54). Further details: interferon: 135 mcg per week for 4 weeks followed by 180 mcg per week for 44 weeks; ribavirin: 400 mg/day escalating to 1200 mg/day for 48 weeks.. Group 2: control (n = 48). Timing of commencement of treatment: 10 to 26 weeks after liver transplantation.
Outcomes	The outcomes reported were virological response and adverse effects.
Notes	Reason for post‐randomisation drop‐outs not stated. Although the authors did not include the patients for analysis, the drop‐out patients were included for virological response outcomes on a poor outcome basis.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	High risk
Incomplete outcome data addressed? All outcomes	High risk	Comment: Post‐randomisation dropouts could be related to outcomes.
Free of selective reporting?	Unclear risk	Comment: Important primary outcomes were not reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.
Free from source of funding bias?	High risk	Quote: 'Grant/Research Support: Roche'.

Davis 2005

Methods	Randomised clinical trial
Participants	Country: USA. Sample size: 18. Post‐randomisation drop‐out: 0 (0%). Revised sample size: 18. Females: 7 (38.9%). Mean age: 53.5 years. Genotype 1 (intervention1): 5 (83.3%). Genotype 1 (intervention2): 4 (66.7%). Genotype 1 (control): 5 (83.3%). Growth factors for bone marrow suppression: no. Inclusion criteria: Adults with decompensated chronic hepatitis C who were listed for liver transplant. Exclusion criteria: 1. Immunoglobulin A (IgA) deficient. 2. History of prior adverse reactions to immune globulin. 3. Hepatitis B surface antigen or anti–human immunodeficiency virus–positive. 4. Extrahepatic malignancy. 5. Receiving cancer chemotherapy. 6. Renal insufficiency. 7. Previously received an organ transplant. 8. Received a graft from an HCV‐positive donor. 9. Received any antiviral agents for hepatitis C in the previous 3 months.
Interventions	The participants were randomly assigned to three groups. Group 1: human hepatitis C antibody enriched immune globulin (n = 6). Further details: 17 intravenous infusions of 200 mg/Kg starting at the time of reperfusion of graft until 14 weeks after transplant. Group 2: human hepatitis C antibody enriched immune globulin (n = 6). Further details: 17 intravenous infusions of 75 mg/Kg starting at the time of reperfusion of graft until 14 weeks after transplant. Group 3: control (n = 6). Timing of commencement of treatment: reperfusion of graft during liver transplantation.
Outcomes	The outcomes reported were re‐transplantation, virological response, and adverse events.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	High risk
Incomplete outcome data addressed? All outcomes	Low risk	Comment: There were no post‐randomisation drop‐outs.
Free of selective reporting?	High risk	Comment: Important primary outcomes were not reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.
Free from source of funding bias?	High risk	Quote: 'C.V.S. (one of the authors) is an employee of Nabi Biopharmaceuticals'.

Mazzaferro 2003

Methods	Randomised clinical trial
Participants	Country: Italy. Sample size: 63. Post‐randomisation drop‐out: 0 (0%). Revised sample size: 63. Females: 15 (23.8%). Mean age: 53 years. Genotype 1 (intervention): not stated. Genotype 1 (control): not stated. Overall genotype 1 (individual groups not stated): 42 (66.7%). Growth factors for bone marrow suppression: no. Inclusion criteria: Liver transplant recipients within 4 weeks after transplant for HCV cirrhosis. Exclusion criteria: 1. Recurrent hepatitis. 2. Rejection.
Interventions	The participants were randomly assigned to three groups. Group 1: ribavirin and interferon (n = 22). Further details: ribavirin 10 mg/kg/day; interferon 3 million units IM thrice weekly (duration not stated). Group 2: interferon (n = 21). Further details: 3 million units IM thrice weekly (duration not stated). Group 3: control (n = 20). Timing of commencement of treatment: within 4 weeks after liver transplantation.
Outcomes	The outcomes reported were virological response and graft rejection.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	High risk
Incomplete outcome data addressed? All outcomes	Low risk	Comment: There were no post‐randomisation drop‐outs.
Free of selective reporting?	High risk	Comment: Important primary outcomes were not reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.

Reddy 2002

Methods	Randomised clinical trial
Participants	Country: USA. Sample size: 32. Post‐randomisation drop‐out: not stated. Revised sample size: 32. Females: 13 (40.6%). Mean age: 50 years. Genotype 1 (intervention): not stated. Genotype 1 (control): not stated. Growth factors for bone marrow suppression: no. Inclusion criteria: Liver transplantation for HCV infection.
Interventions	The participants were randomly assigned to two groups. Group 1: interferon alpha 2b and ribavirin (n = 21). Further details: interferon: 1.5 million units increased to 3 million units thrice weekly SC; ribavirin 400 mg increased to 1000 mg/day. Group 2: control (n = 11). Timing of commencement of treatment: 2 to 4 weeks after liver transplantation.
Outcomes	The outcomes reported were virological response and adverse effects.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	High risk
Free of selective reporting?	High risk	Comment: Important primary outcomes were not reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.

Schiano 2006

Methods	Randomised clinical trial
Participants	Country: USA/ Israel. Sample size: 24. Post‐randomisation drop‐out: 0 (0%). Revised sample size: 24. Females: 1 (4.2%). Mean age: 50.8 years. Genotype 1 (intervention1): 7 (87.5%). Genotype 1 (intervention2): 9 (81.8%). Genotype 1 (control): 5 (100%). Growth factors for bone marrow suppression: no. Inclusion criteria: 1. 18‐65 years of age. 2. Primary LT for HCV infection. 3. HCV RNA positive before liver transplantation by HCV RNA concentration above the local limit of detection within 1 year. 4. Acceptable methods of contraception. Exclusion criteria: 1. Previous LT recipients. 2. Pregnant or breast‐feeding. 3. HIV infection or chronic HBV infection within 1 year. 4. Concurrent transplantation in addition to LT.
Interventions	The participants were randomly assigned to three groups. Group 1: HCV antibody‐68 (high dose) (n = 8). Further details: 120 mg or 240 mg or 480 mg intravenous starting from the anhepatic phase until 8 weeks after transplantation. Group 2: HCV antibody‐68 (low dose) (n = 11). Further details: 20 mg or 40 mg or 80 mg intravenous starting from the anhepatic phase until 8 weeks after transplantation. Group 3: placebo (n = 5). Timing of commencement of treatment: anhepatic phase of liver transplantation.
Outcomes	The outcomes reported were patient survival, virological response and cessation of therapy.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	Low risk	Quote: 'This was a multicenter, randomised, double‐blind, placebo‐controlled, dose‐escalation trial'.
Incomplete outcome data addressed? All outcomes	Low risk	Comment: There were no post‐randomisation drop‐outs.
Free of selective reporting?	High risk	Comment: Important primary outcomes were not reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.
Free from source of funding bias?	High risk	Quote: 'Supported by XTL Biopharmaceuticals Ltd., the developer of HCV‐AbXTL68'.

Sheiner 1998

Methods	Randomised clinical trial
Participants	Country: USA, Israel. Sample size: 86. Post‐randomisation drop‐out: 5 (5.8%). Revised sample size: 81. Females: not stated. Mean age: not stated. Genotype 1 (intervention): 21 (60.0%). Genotype 1 (control): 19 (41.3%). Growth factors for bone marrow suppression: no. Inclusion criteria: 1. Liver transplantation with positive serology for hepatitis C antibody. 2. Age more than 18 years. Exclusion criteria: 1. Retransplantation for recurrent hepatitis C. 2. Transplantation for hepatitis C with hepatocellular carcinoma requiring adjuvant chemotherapy (ie, tumor .5 cm or with vascular invasion). 3. Positive serology for hepatitis B surface antigen. 4. Platelet count was < 50,000 by day 14 after transplantation.
Interventions	The participants were randomly assigned to two groups. Group 1: interferon alpha 2b (n = 35). Further details: 3 million units SC thrice weekly for 52 weeks. Group 2: control (n = 46). Timing of commencement of treatment: within 2 weeks after liver transplantation.
Outcomes	The outcomes reported were survival, re‐transplantation, time to recurrence of viral hepatitis.
Notes	Reasons for post‐randomisation drop‐out: Low WBC (3); adjuvant chemotherapy (1); refusal to enter (1).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	High risk	Quote: 'Protocol biopsies were also reviewed by three pathologists blinded to study group'. Comment: The other outcomes were not assessed by blinded observers.
Incomplete outcome data addressed? All outcomes	High risk	Comment: Post‐randomisation drop‐outs could be related to the outcomes.
Free of selective reporting?	Unclear risk	Comment: Important primary outcomes were not reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.
Free from source of funding bias?	High risk	Quote: 'Supported in part by Ortho Biotech, Raritan, NJ'.

Shergill 2005

Methods	Randomised clinical trial
Participants	Country: USA. Sample size: 44. Post‐randomisation drop‐out: 0 (0%). Revised sample size: 44. Females: not stated. Mean age: not stated. Genotype 1 (intervention): not stated. Genotype 1 (control): not stated. Growth factors for bone marrow suppression: yes. Inclusion criteria: 1. ≥ 18 years of age. 2. Pre‐transplant diagnosis of HCV‐associated cirrhosis. 3. Clinical stability with white cell count (WBC) >3.0/mm3. 4. Hemoglobin > 10.0 g/dL. 5. Platelets > 45 000/mm3. 6. Creatinine (Cr) < 1.5 mg/dL. 7. INR (international normalized ratio) < 2.0. 8. AST (aspartate aminotransferase) < 200 IU. 9. ALT (alanine aminotransferase) < 200 IU. 10.Total bilirubin < 2.5 mg/dL. Exclusion criteria: 1. Serum anti‐HIV or hepatitis B surface antigen positive prior to transplantation. 2. Acute rejection (by clinical and histological criteria) within 14 days of consent. 3. Vascular and biliary complications post‐transplantation resulting in need for interventions. 4. Current untreated infection. 5. Abnormal TSH. 6. Medically uncontrolled psychosis or depression. 7. History of haemoglobinopathies or any cause of chronic haemolysis. 8. Clinically significant retinopathy. 9.Uncontrolled diabetes mellitus. 10.Inability to practice effective contraception (male or female) during the treatment period. 11.Medical history of concomitant autoimmune disease. 12.Continued need for ICU support or unstable cardiopulmonary status including myocardial infarction within preceding 4 weeks.
Interventions	The participants were randomly assigned to two groups. Group 1: ribavirin and interferon (n = 22). Further details: ribavirin: 400 mg escalated to 1000 to 1200 mg for a total period of 48 weeks; interferon: interferon alpha 2b or pegylated interferon alpha 2b (initial patients treated with interferon and later patients treated with pegylated interferon). Interferon started at 1.5 MU daily and increased to 3 MU daily after 2 weeks if tolerated. After 8 weeks, 3 MU thrice weekly. Pegylated interferon: 1.5 mcg/kg/week. Group 2: interferon (n = 22). Timing of commencement of treatment: 2 to 6 weeks after liver transplantation.
Outcomes	The outcomes reported were virological response and adverse effects.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	High risk
Incomplete outcome data addressed? All outcomes	Low risk	Comment: There were no post‐randomisation drop‐outs.
Free of selective reporting?	High risk	Comment: Important primary outcomes were not reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.
Free from source of funding bias?	High risk	Quote: 'The study was supported by Fugisawa Healthcare, Inc., and the UCSF Liver Center P30 DK26743 Clinical and Translational Core'.

Singh 1998

Methods	Randomised clinical trial
Participants	Country: USA. Sample size: 24. Post‐randomisation drop‐out: 0 (0%). Revised sample size: 24. Females: 0 (0%). Mean age: 46 years. Genotype 1 (intervention): 9 (75.0%). Genotype 1 (control): 11 (91.7%). Growth factors for bone marrow suppression: no. Inclusion criteria: Liver transplantation for end‐stage liver disease due to HCV.
Interventions	The participants were randomly assigned to two groups. Group 1: interferon alpha (n = 12). Further details: 3 million units thrice weekly for 6 months. Group 2: control (n = 12). Timing of commencement of treatment: 2 weeks after liver transplantation.
Outcomes	The outcomes reported were patient survival, re‐transplantation, recurrence, and adverse effects.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	High risk
Incomplete outcome data addressed? All outcomes	Low risk	Comment: There were no post‐randomisation drop‐outs.
Free of selective reporting?	Low risk	Comment: Important primary outcomes were reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.

Willems 2002

Methods	Randomised clinical trial
Participants	Country: Canada. Sample size: 16. Post‐randomisation drop‐out: not stated. Revised sample size: 16. Females: not stated. Mean age: not stated. Genotype 1 (intervention): not stated. Genotype 1 (control): not stated. Growth factors for bone marrow suppression: no. Inclusion criteria: Patients undergoing liver transplantation for end‐stage post‐HCV cirrhosis.
Interventions	The participants were randomly assigned to three groups. Group 1: human hepatitis C antibody enriched immune globulin (n = 6). Further details: starting at anhepatic phase with 1500 mg and maintained at 250 mg/biweekly for 48 weeks. Group 2: human hepatitis C antibody enriched immune globulin (n = 3). Further details: starting at anhepatic phase with 500 mg and maintained at 83 mg/biweekly for 48 weeks. Group 3: placebo (n = 7). Timing of commencement of treatment: anhepatic phase of liver transplantation.
Outcomes	The outcome reported was virological response.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Blinding? All outcomes	Low risk	Quote: 'Twenty‐six HCV‐RNA positive OLT candidates were randomly assigned at the time of transplantation to one of three treatment schedules in a double‐blind fashion'.
Free of selective reporting?	High risk	Comment: Important primary outcomes were not reported.
Free from academic bias?	Low risk	Comment: No previous published report of the same intervention by the author.

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos

Study	Reason for exclusion
Beckebaum 2003	Not a randomised clinical trial.
Boillot 1995	Not a randomised clinical trial.
Casanovas 2004	Comment on a trial of antiviral therapy in patients with recurrent HCV infection after liver transplantation.
Castedal 2003	Not a randomised clinical trial.
Catalano 2003	Not a randomised clinical trial.
Ceccherini 2003	Not a randomised clinical trial.
Charlton 2002	Editorial.
Garcia‐Retortillo 2004	Review.
Mazzaferro 1997	Not a randomised clinical trial.
Samuel 2004a	Editorial.
Samuel 2004b	Comments on trial in patients with recurrent HCV infection after liver transplantation.
Taltavull 2004	Comment on a trial of antiviral therapy in patients with recurrent HCV infection after liver transplantation.

Data and analyses

Open in table viewer

Comparison 1. Intervention versus control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 90‐day mortality Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.1 Comparison 1 Intervention versus control, Outcome 1 90‐day mortality.
1.1 Interferon versus control	1	81	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [0.41, 4.19]
1.2 HCV antibody versus placebo	2	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.15, 3.11]
1.3 HCV antibody (high dose) versus HCV antibody (low dose)	2	31	Risk Ratio (M‐H, Fixed, 95% CI)	2.75 [0.30, 25.35]
2 Mortality at maximal follow‐up Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.2 Comparison 1 Intervention versus control, Outcome 2 Mortality at maximal follow‐up.
2.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.05, 5.59]
2.2 Interferon versus control	2	105	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.36, 2.08]
3 Mortality (hazard ratio) Show forest plot	1		Hazard Ratio (Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.3 Comparison 1 Intervention versus control, Outcome 3 Mortality (hazard ratio).
3.1 Interferon versus control	1		Hazard Ratio (Fixed, 95% CI)	0.45 [0.13, 1.56]
4 90‐day retransplantation Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.4 Comparison 1 Intervention versus control, Outcome 4 90‐day retransplantation.
4.1 HCV antibody versus control	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	1.71 [0.09, 32.93]
4.2 HCV antibody (high dose) versus HCV antibody (low dose)	1	12	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.15, 61.74]
5 Re‐transplantation at maximal follow‐up Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.5 Comparison 1 Intervention versus control, Outcome 5 Re‐transplantation at maximal follow‐up.
5.1 Interferon versus control	2	105	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.22, 6.20]
6 Graft rejection requiring re‐transplantation Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.6 Comparison 1 Intervention versus control, Outcome 6 Graft rejection requiring re‐transplantation.
6.1 Interferon versus control	1	31	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Interferon and ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.3 Ribavirin and interferon versus interferon	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Graft rejection requiring steroids or equivalent drugs Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.7 Comparison 1 Intervention versus control, Outcome 7 Graft rejection requiring steroids or equivalent drugs.
7.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.20, 3.27]
7.2 Interferon versus control	3	136	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.68, 1.51]
7.3 Interferon and ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.4 Ribavirin and interferon versus interferon	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Graft rejection (others) Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.8 Comparison 1 Intervention versus control, Outcome 8 Graft rejection (others).
8.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.21 [0.01, 4.28]
8.2 Pegylated interferon and ribavirin versus control	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.10, 3.40]
8.3 Interferon versus control	1	31	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.4 Ribavirin versus control	1	19	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.23, 5.09]
8.5 Interferon and ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.6 Ribavirin and interferon versus interferon	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Cessation of treatment Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.9 Comparison 1 Intervention versus control, Outcome 9 Cessation of treatment.
9.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.44, 2.11]
9.2 Interferon versus control	1	81	Risk Ratio (M‐H, Fixed, 95% CI)	27.42 [1.66, 452.50]
9.3 Ribavirin versus control	1	19	Risk Ratio (M‐H, Fixed, 95% CI)	2.25 [0.10, 49.04]
9.4 HCV antibody versus placebo	2	42	Risk Ratio (M‐H, Fixed, 95% CI)	2.49 [0.52, 11.98]
9.5 HCV antibody (high dose) versus HCV antibody (low dose)	2	31	Risk Ratio (M‐H, Fixed, 95% CI)	1.97 [0.60, 6.45]
10 Reduction in dose Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.10 Comparison 1 Intervention versus control, Outcome 10 Reduction in dose.
10.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	24.70 [1.53, 399.19]
10.2 Ribavirin versus control	1	19	Risk Ratio (M‐H, Fixed, 95% CI)	5.25 [0.31, 89.35]
10.3 Ribavirin and interferon versus interferon	1	44	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.91, 1.53]
10.4 HCV antibody versus placebo	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	5.71 [0.89, 36.82]
10.5 HCV antibody (high dose) versus HCV antibody (low dose)	1	12	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.64, 2.44]
11 Anaemia Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.11 Comparison 1 Intervention versus control, Outcome 11 Anaemia.
11.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.09, 2.03]
11.2 Pegylated interferon and ribavirin versus control	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	8.0 [1.05, 60.86]
11.3 Ribavirin versus control	1	19	Risk Ratio (M‐H, Fixed, 95% CI)	6.75 [0.41, 110.01]
11.4 Interferon and ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	13.64 [0.88, 210.72]
12 Leukopenia Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.12 Comparison 1 Intervention versus control, Outcome 12 Leukopenia.
12.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [0.45, 3.73]
12.2 Interferon versus control	1	24	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.27, 94.34]
13 Renal failure Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.13 Comparison 1 Intervention versus control, Outcome 13 Renal failure.
13.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.09, 2.03]
14 Depression Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.14 Comparison 1 Intervention versus control, Outcome 14 Depression.
14.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	1.79 [0.48, 6.77]
14.2 Pegylated interferon and ribavirin versus control	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
15 Rapid virological response Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.15 Comparison 1 Intervention versus control, Outcome 15 Rapid virological response.
15.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.76, 1.03]
15.2 Pegylated interferon and ribavirin versus control	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.86, 1.01]
16 Early virological response Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.16 Comparison 1 Intervention versus control, Outcome 16 Early virological response.
16.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.71, 1.01]
16.2 Pegylated interferon and ribavirin versus control	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.72, 0.98]
17 End of treatment virological response Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.17 Comparison 1 Intervention versus control, Outcome 17 End of treatment virological response.
17.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.71, 1.01]
17.2 Interferon versus control	1	81	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.39, 1.04]
17.3 Ribavirin and interferon versus interferon	1	44	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.63, 1.03]
17.4 HCV antibody versus placebo	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.74, 1.35]
17.5 HCV antibody (high dose) versus HCV antibody (low dose)	1	12	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.75, 1.34]
18 Sustained virological response Show forest plot	8		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.18 Comparison 1 Intervention versus control, Outcome 18 Sustained virological response.
18.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.81, 1.05]
18.2 Pegylated interferon and ribavirin versus control	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.71, 0.96]
18.3 Interferon versus control	2	55	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.70, 1.39]
18.4 Ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.56, 1.30]
18.5 Interferon and ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.73, 1.22]
18.6 Ribavirin and interferon versus interferon	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.59, 1.20]
18.7 HCV antibody versus placebo	3	58	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.84, 1.19]
18.8 HCV antibody (high dose) versus HCV antibody (low dose)	3	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.85, 1.17]
19 Virological titre at maximal follow‐up Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.19 Comparison 1 Intervention versus control, Outcome 19 Virological titre at maximal follow‐up.
19.1 Pegylated interferon versus control	1	54	Mean Difference (IV, Fixed, 95% CI)	0.20 [‐1.35, 1.75]
20 Recurrence (hazard ratio) Show forest plot	2		Hazard Ratio (Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.20 Comparison 1 Intervention versus control, Outcome 20 Recurrence (hazard ratio).
20.1 Interferon versus control	2		Hazard Ratio (Fixed, 95% CI)	0.87 [0.61, 1.24]
21 Fibrosis worsening Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.21 Comparison 1 Intervention versus control, Outcome 21 Fibrosis worsening.
21.1 HCV antibody versus placebo	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.17, 4.43]
21.2 HCV antibody (high dose) versus HCV antibody (low dose)	1	12	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.02, 6.86]
22 Fibrosis score at maximal follow‐up Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.22 Comparison 1 Intervention versus control, Outcome 22 Fibrosis score at maximal follow‐up.
22.1 Pegylated interferon versus control	1	54	Mean Difference (IV, Fixed, 95% CI)	‐0.50 [‐1.21, 0.21]
23 Activity worsening Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.23 Comparison 1 Intervention versus control, Outcome 23 Activity worsening.
23.1 Ribavirin versus control	1	19	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.67, 1.78]
23.2 HCV antibody versus placebo	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	1.75 [0.51, 5.98]
23.3 HCV antibody (high dose) versus HCV antibody (low dose)	1	12	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.50, 3.55]
24 Activity score at maximal follow‐up Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.24 Comparison 1 Intervention versus control, Outcome 24 Activity score at maximal follow‐up.
24.1 Pegylated interferon versus control	1	54	Mean Difference (IV, Fixed, 95% CI)	‐1.70 [‐4.06, 0.66]

Figure 1

Reference flow

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Figure 2

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

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Figure 3

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

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Analysis 1.1

Comparison 1 Intervention versus control, Outcome 1 90‐day mortality.

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Analysis 1.2

Comparison 1 Intervention versus control, Outcome 2 Mortality at maximal follow‐up.

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Analysis 1.3

Comparison 1 Intervention versus control, Outcome 3 Mortality (hazard ratio).

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Analysis 1.4

Comparison 1 Intervention versus control, Outcome 4 90‐day retransplantation.

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Analysis 1.5

Comparison 1 Intervention versus control, Outcome 5 Re‐transplantation at maximal follow‐up.

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Analysis 1.6

Comparison 1 Intervention versus control, Outcome 6 Graft rejection requiring re‐transplantation.

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Analysis 1.7

Comparison 1 Intervention versus control, Outcome 7 Graft rejection requiring steroids or equivalent drugs.

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Analysis 1.8

Comparison 1 Intervention versus control, Outcome 8 Graft rejection (others).

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Analysis 1.9

Comparison 1 Intervention versus control, Outcome 9 Cessation of treatment.

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Analysis 1.10

Comparison 1 Intervention versus control, Outcome 10 Reduction in dose.

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Analysis 1.11

Comparison 1 Intervention versus control, Outcome 11 Anaemia.

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Analysis 1.12

Comparison 1 Intervention versus control, Outcome 12 Leukopenia.

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Analysis 1.13

Comparison 1 Intervention versus control, Outcome 13 Renal failure.

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Analysis 1.14

Comparison 1 Intervention versus control, Outcome 14 Depression.

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Analysis 1.15

Comparison 1 Intervention versus control, Outcome 15 Rapid virological response.

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Analysis 1.16

Comparison 1 Intervention versus control, Outcome 16 Early virological response.

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Analysis 1.17

Comparison 1 Intervention versus control, Outcome 17 End of treatment virological response.

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Analysis 1.18

Comparison 1 Intervention versus control, Outcome 18 Sustained virological response.

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Analysis 1.19

Comparison 1 Intervention versus control, Outcome 19 Virological titre at maximal follow‐up.

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Analysis 1.20

Comparison 1 Intervention versus control, Outcome 20 Recurrence (hazard ratio).

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Analysis 1.21

Comparison 1 Intervention versus control, Outcome 21 Fibrosis worsening.

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Analysis 1.22

Comparison 1 Intervention versus control, Outcome 22 Fibrosis score at maximal follow‐up.

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Analysis 1.23

Comparison 1 Intervention versus control, Outcome 23 Activity worsening.

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Analysis 1.24

Comparison 1 Intervention versus control, Outcome 24 Activity score at maximal follow‐up.

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Comparison 1. Intervention versus control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 90‐day mortality Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Interferon versus control	1	81	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [0.41, 4.19]
1.2 HCV antibody versus placebo	2	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.15, 3.11]
1.3 HCV antibody (high dose) versus HCV antibody (low dose)	2	31	Risk Ratio (M‐H, Fixed, 95% CI)	2.75 [0.30, 25.35]
2 Mortality at maximal follow‐up Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.05, 5.59]
2.2 Interferon versus control	2	105	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.36, 2.08]
3 Mortality (hazard ratio) Show forest plot	1		Hazard Ratio (Fixed, 95% CI)	Subtotals only

3.1 Interferon versus control	1		Hazard Ratio (Fixed, 95% CI)	0.45 [0.13, 1.56]
4 90‐day retransplantation Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 HCV antibody versus control	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	1.71 [0.09, 32.93]
4.2 HCV antibody (high dose) versus HCV antibody (low dose)	1	12	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.15, 61.74]
5 Re‐transplantation at maximal follow‐up Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 Interferon versus control	2	105	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.22, 6.20]
6 Graft rejection requiring re‐transplantation Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 Interferon versus control	1	31	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Interferon and ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.3 Ribavirin and interferon versus interferon	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Graft rejection requiring steroids or equivalent drugs Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.20, 3.27]
7.2 Interferon versus control	3	136	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.68, 1.51]
7.3 Interferon and ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.4 Ribavirin and interferon versus interferon	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Graft rejection (others) Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.21 [0.01, 4.28]
8.2 Pegylated interferon and ribavirin versus control	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.10, 3.40]
8.3 Interferon versus control	1	31	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.4 Ribavirin versus control	1	19	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.23, 5.09]
8.5 Interferon and ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.6 Ribavirin and interferon versus interferon	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Cessation of treatment Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.44, 2.11]
9.2 Interferon versus control	1	81	Risk Ratio (M‐H, Fixed, 95% CI)	27.42 [1.66, 452.50]
9.3 Ribavirin versus control	1	19	Risk Ratio (M‐H, Fixed, 95% CI)	2.25 [0.10, 49.04]
9.4 HCV antibody versus placebo	2	42	Risk Ratio (M‐H, Fixed, 95% CI)	2.49 [0.52, 11.98]
9.5 HCV antibody (high dose) versus HCV antibody (low dose)	2	31	Risk Ratio (M‐H, Fixed, 95% CI)	1.97 [0.60, 6.45]
10 Reduction in dose Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

10.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	24.70 [1.53, 399.19]
10.2 Ribavirin versus control	1	19	Risk Ratio (M‐H, Fixed, 95% CI)	5.25 [0.31, 89.35]
10.3 Ribavirin and interferon versus interferon	1	44	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.91, 1.53]
10.4 HCV antibody versus placebo	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	5.71 [0.89, 36.82]
10.5 HCV antibody (high dose) versus HCV antibody (low dose)	1	12	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.64, 2.44]
11 Anaemia Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

11.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.09, 2.03]
11.2 Pegylated interferon and ribavirin versus control	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	8.0 [1.05, 60.86]
11.3 Ribavirin versus control	1	19	Risk Ratio (M‐H, Fixed, 95% CI)	6.75 [0.41, 110.01]
11.4 Interferon and ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	13.64 [0.88, 210.72]
12 Leukopenia Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

12.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [0.45, 3.73]
12.2 Interferon versus control	1	24	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.27, 94.34]
13 Renal failure Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

13.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.09, 2.03]
14 Depression Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

14.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	1.79 [0.48, 6.77]
14.2 Pegylated interferon and ribavirin versus control	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
15 Rapid virological response Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

15.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.76, 1.03]
15.2 Pegylated interferon and ribavirin versus control	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.86, 1.01]
16 Early virological response Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

16.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.71, 1.01]
16.2 Pegylated interferon and ribavirin versus control	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.72, 0.98]
17 End of treatment virological response Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

17.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.71, 1.01]
17.2 Interferon versus control	1	81	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.39, 1.04]
17.3 Ribavirin and interferon versus interferon	1	44	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.63, 1.03]
17.4 HCV antibody versus placebo	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.74, 1.35]
17.5 HCV antibody (high dose) versus HCV antibody (low dose)	1	12	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.75, 1.34]
18 Sustained virological response Show forest plot	8		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

18.1 Pegylated interferon versus control	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.81, 1.05]
18.2 Pegylated interferon and ribavirin versus control	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.71, 0.96]
18.3 Interferon versus control	2	55	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.70, 1.39]
18.4 Ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.56, 1.30]
18.5 Interferon and ribavirin versus control	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.73, 1.22]
18.6 Ribavirin and interferon versus interferon	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.59, 1.20]
18.7 HCV antibody versus placebo	3	58	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.84, 1.19]
18.8 HCV antibody (high dose) versus HCV antibody (low dose)	3	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.85, 1.17]
19 Virological titre at maximal follow‐up Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

19.1 Pegylated interferon versus control	1	54	Mean Difference (IV, Fixed, 95% CI)	0.20 [‐1.35, 1.75]
20 Recurrence (hazard ratio) Show forest plot	2		Hazard Ratio (Fixed, 95% CI)	Subtotals only

20.1 Interferon versus control	2		Hazard Ratio (Fixed, 95% CI)	0.87 [0.61, 1.24]
21 Fibrosis worsening Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

21.1 HCV antibody versus placebo	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.17, 4.43]
21.2 HCV antibody (high dose) versus HCV antibody (low dose)	1	12	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.02, 6.86]
22 Fibrosis score at maximal follow‐up Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

22.1 Pegylated interferon versus control	1	54	Mean Difference (IV, Fixed, 95% CI)	‐0.50 [‐1.21, 0.21]
23 Activity worsening Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

23.1 Ribavirin versus control	1	19	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.67, 1.78]
23.2 HCV antibody versus placebo	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	1.75 [0.51, 5.98]
23.3 HCV antibody (high dose) versus HCV antibody (low dose)	1	12	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.50, 3.55]
24 Activity score at maximal follow‐up Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

24.1 Pegylated interferon versus control	1	54	Mean Difference (IV, Fixed, 95% CI)	‐1.70 [‐4.06, 0.66]

Comparison 1. Intervention versus control

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Referencias

References to studies included in this review

Belli 2001 {published data only}

Chalasani 2005 {published data only}

Charlton 2007 {published data only}

Davis 2005 {published data only}

Mazzaferro 2003 {published data only}

Reddy 2002 {published data only}

Schiano 2006 {published data only}

Sheiner 1998 {published data only}

Shergill 2005 {published data only}

Singh 1998 {published data only}

Willems 2002 {published data only}

References to studies excluded from this review

Beckebaum 2003 {published data only}

Boillot 1995 {published data only}

Casanovas 2004 {published data only}

Castedal 2003 {published data only}

Catalano 2003 {published data only}

Ceccherini 2003 {published data only}

Charlton 2002 {published data only}

Garcia‐Retortillo 2004 {published data only}

Mazzaferro 1997 {published data only}

Samuel 2004a {published data only}

Samuel 2004b {published data only}

Taltavull 2004 {published data only}

Additional references

Afdhal 2004

Berenguer 2003

Bombuy 2004

Brok 2010

Cameron 2006

Cescon 2006

Corno 2006

DeMets 1987

DerSimonian 1986

Dieterich 2003

Eason 2001

Egger 1997

Forman 2002

Ghobrial 1999

Gluud 2010

Gurusamy 2009

Higgins 2002

Higgins 2009

Jain 2002

Kamath 2001

Kjaergard 2001

Koneru 2005

Lim 2006

Macaskill 2001

Moher 1998

Newell 1992

NHS UK Transplant

OPTN/SRTR 2005

Parmar 1998

RevMan 2008 [Computer program]

Royle 2003

Schulz 1995

Sharvadze 2006

Sharvadze 2007

Shiffman 2006

Sugo 2003

Sweeting 2004

Tierney 2007

Wood 2008

Yilmaz 2007

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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