Risk factors for cytomegalovirus reactivation after liver transplantation: can pre-transplant cytomegalovirus antibody titers predict outcome?

Abstract

Despite preexisting cytomegalovirus (CMV) immunity, CMV-seropositive liver transplantation (LT) patients remain at risk of CMV infection. We hypothesized that the pre-transplant CMV antibody titer correlates with the risk of CMV reactivation. We conducted a retrospective study of CMV-seropositive LT recipients who did not receive anti-CMV prophylaxis from 2007 to 2013. The pre-transplant CMV immunoglobulin G (IgG) titer, which was measured with an enzyme-linked fluorescent immunoassay, was assessed as a risk factor for CMV reactivation with multivariate Cox proportional hazards models. The population consisted of 225 CMV-seropositive LT patients with a median age of 57 years (interquartile range, 47-62 years). The CMV titer distributions were as follows: <60 (40%) and ≥60 AU/mL (60%). The Kaplan-Meier estimates for CMV infection were 17% at 3 months, 18% at 6 months, and 19% at 12 months after transplantation. In a univariate analysis, a marginally significant increased risk of CMV infection was seen in LT recipients with a pre-transplant CMV IgG titer<60 AU/mL versus ≥60 AU/mL [hazard ratio (HR), 1.79; 95% confidence interval (CI), 0.98-3.28 (P=0.06)]. This risk was statistically significant in the subgroup of recipients who received allografts from CMV-seropositive donors [HR, 2.21; 95% CI, 1.15-4.26 (P=0.02)]. In a multivariate analysis, a pre-transplant CMV IgG titer<60 AU/mL was significantly associated with CMV infection [HR, 3.11; 95% CI, 1.60-6.03 (P<0.001)]. The other risk factors were high body mass index, donor CMV seropositivity, prolonged cold ischemic time, use of an interleukin-2 receptor antagonist for induction therapy, and high numbers of post-transplant infections. A lower pre-transplant CMV antibody titer is significantly associated with CMV infection after LT. Quantitative measurement of CMV-specific humoral immunity may have a potential role in improving the CMV prevention strategy in CMV-seropositive LT recipients.