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 ¼ 483) were pooled with a random effects model; five single-arm studies (n ¼ 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) ¼ 1.00-3.29, P ¼ 0.05, I2 ¼ 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI ¼ 1.05-3.67, P ¼ 0.035, I2 ¼ 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P ¼ 0.04) but not with 450 mg of VGC daily (P ¼ 0.76). The risk of leukopenia with VGC was 1.87 (95% CI ¼ 1.03-3.37, P ¼ 0.04, I 2 ¼ 0%). In single-arm trials, the overall CMV disease rate was 12% (95% CI ¼ 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI ¼ 10%-38%, P ¼ 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.

Histopathology of viral infections of the lung

“…7,19 Given the severity of illness, prophylactic antiviral therapy with valganciclovir or ganciclovir is routinely administered to at-risk groups such as solid organ transplant recipients who are CMV seronegative and receive an organ from a CMV seropositive donor. 6,7 Mild disease usually resolves spontaneously and does not require treatment, whereas severe disease is potentially life-threatening and is treated with valganciclovir or ganciclovir. 19…”

“…CMV is the most common cause of viral pneumonia in the immunocompromised host and prophylactic antiviral therapy is commonly administered in patients who are at risk for reactivation. 6 RSV is also an important cause of morbidity and mortality in immunosuppressed patients. 7 Finally, some vaccinepreventable diseases such as measles pneumonia have increased in prevalence due to low vaccination rates in some populations and increased international travel.…”

Prevention of cytomegalovirus following solid organ transplantation: A literature review

“…Following this landmark trial, several single‐center studies sought to compare CMV disease in high‐risk liver recipients receiving oral ganciclovir vs. valganciclovir prophylaxis with conflicting results . A paper recently accepted for publication summarizes findings from five controlled studies and five single‐arm studies (n = 863) looking at the risk of CMV disease in liver recipients treated with prophylactic valganciclovir for three months . The overall relative risk of CMV disease with valganciclovir compared with ganciclovir was 1.81, a result that just reached statistical significance (95% CI, 1.00–3.29, p = 0.05) .…”

“…A paper recently accepted for publication summarizes findings from five controlled studies and five single‐arm studies (n = 863) looking at the risk of CMV disease in liver recipients treated with prophylactic valganciclovir for three months . The overall relative risk of CMV disease with valganciclovir compared with ganciclovir was 1.81, a result that just reached statistical significance (95% CI, 1.00–3.29, p = 0.05) . For high‐risk D+/R− patients, the risk was 1.96 (95% CI, 1.05–3.67 p = 0.035).…”

“…As an explanation for the inferiority of valganciclovir prophylaxis in liver transplant recipients observed across multiple studies, it has been hypothesized that the post‐transplanted liver may be inefficient at converting valganciclovir to ganciclovir. It has also been postulated that concurrent use of mycophenolate mofetil, which also requires the liver esterase for conversion to MPA, might be contributory .…”