Risk of cytomegalovirus disease in high-risk liver transplant recipients on valganciclovir prophylaxis: a systematic review and meta-analysis.

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, I(2) = 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, I(2) = 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, I(2) = 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.

Impact of sarcopenia on mortality in patients undergoing liver re-transplantation.

BACKGROUND: Sarcopenia, which is a loss of skeletal muscle mass, has been reported to increase post-transplant mortality and morbidity in patients undergoing the first liver transplant. Cross-sectional imaging modalities typically determine sarcopenia in patients with cirrhosis by measuring core abdominal musculatures. However, there is limited evidence for sarcopenia related outcomes in patients undergoing liver re-transplantation (re-OLT). AIM: To evaluate the risk of mortality in patients with pre-existing sarcopenia following liver re-OLT. METHODS: This is a retrospective study of all adult patients who had undergone a liver re-OLT at the University of Nebraska Medical Center from January 1, 2007 to January 1, 2017. We divided patients into sarcopenia and no sarcopenia groups. "TeraRecon AquariusNet 4.4.12.194" software was used to evaluate computed tomography or magnetic resonance imaging of the patients done within one year prior to their re-OLT, to calculate the Psoas muscle area at L3-L4 intervertebral disc. We defined cutoffs for sarcopenia as < 1561 mm2 for males and < 1464 mm2 for females. The primary outcome was to compare 90 d, one, and 5-year survival rates. We also compared complications after re-OLT, length of stay, and re-admission within 30 d. Survival analysis was performed with Kaplan-Meier survival analysis. Continuous variables were evaluated with Wilcoxon rank-sum tests. Categorical variables were evaluated with Fisher's exact tests. RESULTS: Fifty-seven patients were included, 32 males: 25 females, median age 50 years. Two patients were excluded due to incomplete information. Overall, 47% (26) of patients who underwent re-OLT had sarcopenia. Females were found to have significantly more sarcopenia than males (73% vs 17%, P < 0.001). Median model for end stage liver disease at re-OLT was 28 in both sarcopenia and no sarcopenia groups. Patients in the no sarcopenia group had a trend of longer median time between the first and second transplant (36.5 mo vs 16.7 mo). Biological markers, outcome parameters, and survival at 90 d, 1 and 5 years, were similar between the two groups. Sarcopenia in re-OLT at our center was noted to be twice as common (47%) as historically reported in patients undergoing primary liver transplantation. CONCLUSION: Overall survival and outcome parameters were no different in those with and without the evidence of sarcopenia after re-OLT.