Publication: Biopsy-proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal.
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Identifiers
Date
2015-12-18
Authors
Rodriguez-Peralvarez, Manuel
Rico-Juri, Jose M
Tsochatzis, Emmanuel
Burra, Patrizia
De la Mata, Manuel
Lerut, Jan
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Abstract
Biopsy-proven acute cellular rejection (ACR) is the primary efficacy endpoint in most randomized trials evaluating immunosuppression in liver transplantation. However, ACR is not a major cause of graft loss, and a certain grade of immune activation may be even beneficial for long-term graft acceptance. Validated criteria to select candidates for liver biopsy are lacking, and routine clinical practice relies on liver tests, which are inaccurate markers of ACR. Indeed, both the agreement among clinicians to select candidates for liver biopsy and the correlation between the clinical suspicion of ACR and histological findings are poor. In randomized trials evaluating immunosuppression protocols, this concern grows exponentially due to the open-label and multicenter nature of most studies. Therefore, biopsy-proven ACR is a suboptimal efficacy endpoint given its limited impact on prognosis and the heterogeneous diagnosis, which may increase the risk of bias. Chronic rejection and/or graft loss would be more appropriate endpoints, but would certainly require larger studies with prolonged surveillances. An objective method to select candidates for liver biopsy is therefore urgently needed, and only severe episodes of histological ACR should be considered as potentially harmful. Emerging surrogate markers of ACR and antibody-mediated rejection require further investigation to determine their clinical role.
Description
MeSH Terms
Biomarkers
Biopsy
Graft rejection
Graft survival
Humans
Immunosuppression therapy
Liver
Liver failure
Liver transplantation
Randomized controlled trials as topic
Treatment outcome
Biopsy
Graft rejection
Graft survival
Humans
Immunosuppression therapy
Liver
Liver failure
Liver transplantation
Randomized controlled trials as topic
Treatment outcome
DeCS Terms
Biomarcadores
Biopsia
Fallo hepático
Rechazo de injerto
Resultado del tratamiento
Supervivencia de injerto
Terapia de inmunosupresión
Trasplante de hígado
Biopsia
Fallo hepático
Rechazo de injerto
Resultado del tratamiento
Supervivencia de injerto
Terapia de inmunosupresión
Trasplante de hígado
CIE Terms
Keywords
Acute cellular rejection, Liver biopsy, Liver transplantation, Randomized controlled trial, Transaminases
Citation
Rodríguez-Perálvarez M, Rico-Juri JM, Tsochatzis E, Burra P, De la Mata M, Lerut J. Biopsy-proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal. Transpl Int. 2016 Sep;29(9):961-73