Risk of cytomegalovirus disease in high-risk liver transplant recipients on valganciclovir prophylaxis

A systematic review and meta-Analysis

Andre C Kalil, Cezarina Mindru, Jean F. Botha, Wendy J. Grant, David F Mercer, Marco A Olivera-Martinez, Megan A. McCartan, Timothy M McCashland, Alan Norman Langnas, Diana F Florescu

Research output: Contribution to journalReview article

23 Citations (Scopus)

Abstract

Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-Arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I2 = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I2 = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I2= 0%). In single-Arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients. Liver Transpl, 2012. © 2012 AASLD.

Original languageEnglish (US)
Pages (from-to)1440-1447
Number of pages8
JournalLiver Transplantation
Volume18
Issue number12
DOIs
StatePublished - Dec 1 2012

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Cytomegalovirus
Meta-Analysis
Liver
Confidence Intervals
Leukopenia
valganciclovir
Transplant Recipients
Off-Label Use
Ganciclovir
United States Food and Drug Administration
Tissue Donors

ASJC Scopus subject areas

  • Surgery
  • Hepatology
  • Transplantation

Cite this

@article{bf40405397724cb2bca1c1aa0ea91bbb,
title = "Risk of cytomegalovirus disease in high-risk liver transplant recipients on valganciclovir prophylaxis: A systematic review and meta-Analysis",
abstract = "Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-Arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95{\%} confidence interval (CI) = 1.00-3.29, P = 0.05, I2 = 0{\%}]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95{\%} CI = 1.05-3.67, P = 0.035, I2 = 0{\%}). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95{\%} CI = 1.03-3.37, P = 0.04, I2= 0{\%}). In single-Arm trials, the overall CMV disease rate was 12{\%} (95{\%} CI = 9{\%}-16{\%}, P < 0.001), and the rate for high-risk patients was 20{\%} (95{\%} CI = 10{\%}-38{\%}, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients. Liver Transpl, 2012. {\circledC} 2012 AASLD.",
author = "Kalil, {Andre C} and Cezarina Mindru and Botha, {Jean F.} and Grant, {Wendy J.} and Mercer, {David F} and Olivera-Martinez, {Marco A} and McCartan, {Megan A.} and McCashland, {Timothy M} and Langnas, {Alan Norman} and Florescu, {Diana F}",
year = "2012",
month = "12",
day = "1",
doi = "10.1002/lt.23530",
language = "English (US)",
volume = "18",
pages = "1440--1447",
journal = "Liver Transplantation",
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number = "12",

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TY - JOUR

T1 - Risk of cytomegalovirus disease in high-risk liver transplant recipients on valganciclovir prophylaxis

T2 - A systematic review and meta-Analysis

AU - Kalil, Andre C

AU - Mindru, Cezarina

AU - Botha, Jean F.

AU - Grant, Wendy J.

AU - Mercer, David F

AU - Olivera-Martinez, Marco A

AU - McCartan, Megan A.

AU - McCashland, Timothy M

AU - Langnas, Alan Norman

AU - Florescu, Diana F

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-Arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I2 = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I2 = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I2= 0%). In single-Arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients. Liver Transpl, 2012. © 2012 AASLD.

AB - Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-Arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I2 = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I2 = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I2= 0%). In single-Arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients. Liver Transpl, 2012. © 2012 AASLD.

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