Cytomegalovirus Reactivation Is Associated With Lower Rates of Hepatocellular Carcinoma Recurrence After Liver Transplantation

Abstract

In patients with hepatocellular carcinoma (HCC), undergoing liver transplantation (LT), cytomegalovirus reactivation (CMVr) may modulate the immune system to prevent tumor recurrence. In this multicenter retrospective study (2010–2015) involving 15 institutions, we assessed the effect of early CMVr in tumor recurrence rates among 771-LT HCC patients with tacrolimus-based immunosuppression (88% men, mean age 58 years). CMV prophylaxis was implemented for 19.7% of patients, while the rest were managed with preemptive therapy. The Milan criteria were met by 88% of patients. Microvascular invasion was present in 12.7% of explanted livers. The serum AFP level before transplantation was 5.1 (3–15) ng/mL. After a median follow-up of 7.4 years, 101 patients (13%) experienced HCC recurrence. CMVr occurred in 235 patients (30.5%) at a median of 41.5 days post-LT and 42 patients (5.6%) had CMV disease. Cumulative exposure to tacrolimus within the first 3 months after LT was similar among patients with and without CMVr. In a multivariate Cox regression analysis, factors associated with an increased rate of HCC recurrence included microvascular invasion [HR:2.82, CI95%:1.55–5.14; p 0.0001], donation after circulatory determination of death [HR:4.43,CI95%:1.52–12.9; p 0.006) and diameter of the main nodule at explant [HR:1.04, CI95%:1.02–1.06; p < 0.001]. Meanwhile CMVr [HR:0.46, CI95%:0.23–0.93, p 0.031] and MELD [HR:0.93, CI95%:0.87–0.99; p0.017] exhibited protective effects. In conclusion, early CMVr may protect against HCC recurrence. The underlying immune mechanisms warrant further investigation.