The authors concluded that interferon-based treatments for hepatitis C virus-related liver disease have poor efficacy and safety in renal transplant patients. However, the evidence was limited and came from a small number of observational studies that were often retrospective. Recommendations about the need for further research appear justified.

To evaluate the efficacy and safety of interferon (IFN)-based treatments for hepatitis C virus (HCV)-related liver disease in renal transplant patients.

MEDLINE, Current Contents, the Cochrane Library and selected specialist journals were searched for published peer-reviewed studies; the search terms were reported. In addition, reference lists in reviews and published clinical trials were screened. English and non-English language reports were eligible. Abstracts and interim reports were excluded.

Study designs of evaluations included in the review

Clinical trials were eligible for inclusion. In the included studies, the duration of follow-up ranged from 5.25 to 84 months after the start of IFN treatment.

Specific interventions included in the review

Studies of IFN either alone or in combination with ribavirin were eligible for inclusion. IFN was always administered subcutaneously. The patients also received a variety of immunosuppressive drugs.

Participants included in the review

It was clear that studies of renal transplant patients with hepatitis C were to be included. Studies of previously treated patients, nonresponders or relapsers were excluded, as were studies of patients on maintenance dialysis. The mean age of patients in the included studies ranged from 36 to 48 years, and most were men (range: 54 to 100%). Half of the included studies were conducted in Asian countries (Japan, Hong Kong and Taiwan). In all but one study, in which patients had acute de novo hepatitis, the patients had chronic hepatitis C.

Outcomes assessed in the review

Studies that reported adequate data about the sustained virological response (SVR) and/or drop-out rate were eligible for inclusion. SVR was defined as the disappearance of HCV viraemia by polymerase chain reaction at least 6 months after completion of treatment. Viral response had to be measured using the polymerase chain reaction method. The review also assessed sustained biochemical response, which was defined as the normalisation of alanine aminotransferase levels at least 6 months after treatment completion.

How were decisions on the relevance of primary studies made?

It appears that more than one reviewer selected the studies and reached agreement about inclusions.

The authors did not state that they assessed validity.

Two reviewers independently extracted the data and resolved any disagreements by consensus. The response rates were extracted or calculated on an intention-to-treat basis.

How were the studies combined?

Pooled SVR and drop-out rates with 95% confidence intervals (CIs) were calculated using the DerSimonian and Laird random-effects model. Publication bias was assessed using the rank correlation test of Begg and Mazumdar and the regression asymmetry test of Egger.

How were differences between studies investigated?

Heterogeneity was assessed using the Cochran Q test and the I-squared statistic.
Potential sources of heterogeneity were discussed. Summary estimates were calculated for some subgroups. Meta-regression was used to examine the influence of a range of variables on the summary estimates. The analyses were repeated using a fixed-effect model.

Twelve studies (n=102) were included: one non-randomised controlled trial (n=14) and 11 cohort studies (6 prospective and 5 retrospective). The sample size ranged from 3 to 14.

Nine studies evaluated IFN alone and three evaluated IFN plus ribavirin.

The overall pooled SVR rate was 18% (95% CI: 7, 29; range: 5 to 50) and the drop-out rate was 35% (95% CI: 20, 50; range: 4 to 88) Significant heterogeneity was observed for both analyses (SVR: Q statistic, p=0.08 and I-squared 45%; drop-out rate: p=0.0014 and I-squared 76%).

Overall, 39 patients (38%) dropped out. The reasons for withdrawal were graft dysfunction (n=28; 72%), fever or flu-like symptoms (n=5; 5%), sepsis (n=2; 2%) and depression, encephalopathy and haematological changes (n=1 for each).

There was no evidence of significant publication bias (p-values ranged from 0.266 to 0.150 for Begg’s test and from 0.099 to 0.105 for Egger’s test). The results of the subgroup and meta-regression analyses were also reported.

IFN-based treatments after renal transplant have poor efficacy and safety. There is a need for safer and more effective treatments.

The review addressed a clear question with clear inclusion criteria. Several relevant sources were searched and non-English language reports were eligible, but no attempts were made to minimise publication bias. The potential for publication bias was assessed and none was found. Methods were used to minimise reviewer error and bias in the selection of studies and extraction of data. Study validity was not assessed and several studies were retrospective in design, so the results from these studies and any synthesis might not be reliable. The data were pooled using meta-analyses. However, there was significant heterogeneity between the studies for both primary outcomes, which could indicate that pooling the data was not appropriate. The authors acknowledged the limitations of the evidence in their discussion. The authors’ conclusions reflect the limited evidence from a small number of observational studies. Their recommendations about the need for further research appear justified.

Practice: The authors stated that clinicians need to balance the benefits of IFN treatment after renal transplant against the risk of graft rejection.

Research: The authors stated the need for more effective and safer treatments for renal transplant patients with HCV.

Project Glomerulonephritis.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.