title: 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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN; Somdech Phra Debaratana Medical Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Jackrapong
authors.initials: J
authors.lastname: Bruminhent
authors.forename: Charat
authors.initials: C
authors.lastname: Thongprayoon
authors.forename: Ross A
authors.initials: RA
authors.lastname: Dierkhising
authors.forename: Walter K
authors.initials: WK
authors.lastname: Kremers
authors.forename: Elitza S
authors.initials: ES
authors.lastname: Theel
authors.forename: Raymund R
authors.initials: RR
authors.lastname: Razonable
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014775:Virus Activation
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D007074:Immunoglobulin G