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.
