Delayed-onset primary cytomegalovirus disease after liver transplantation

Abstract

Clinical practice guidelines recommend antiviral prophylaxis to cytomegalovirus (CMV) donor-positive/recipient-negative (Dϩ/RϪ) liver transplant recipients. We assessed the outcome of this strategy by determining the incidence, clinical features, and risk factors of CMV disease among CMV Dϩ/RϪ liver transplant recipients who received antiviral prophylaxis. Sixty-seven CMV Dϩ/RϪ liver transplant recipients (mean age Ϯ standard deviation: 49.5 Ϯ 11.4 years; 75% male) received oral ganciclovir [n ϭ 9 (13%)] or valganciclovir [n ϭ 58 (87%)] prophylaxis for a median duration of 92 days (interquartile range: 91-100). No breakthrough CMV disease was observed during antiviral prophylaxis. However, primary CMV disease was observed in 2%, 25%, 27%, 27%, and 29% of patients at 1, 3, 6, 12, and 24 months, respectively, after antiviral prophylaxis was stopped. The incidence of delayed-onset primary CMV disease was similar between those who received oral ganciclovir and valganciclovir. Nine (47%) patients had CMV syndrome, 8 (42%) had gastrointestinal CMV disease, and 2 (11%) had CMV hepatitis. Female patients (P ϭ 0.01) and younger age at transplant (P ϭ 0.03) were associated with an increased risk, whereas diabetes mellitus (P Ͻ 0.001) was significantly associated with a lower risk of delayed-onset primary CMV disease. Allograft loss or mortality occurred in 8 (12%) patients during the median follow-up period of 3.31 (range: 0.8-5.9) years. No significant association was observed between CMV disease and patient and allograft survival. In conclusion, CMV disease remains a common complication in CMV Dϩ/RϪ liver transplant patients during the contemporary era of antiviral prophylaxis. Female patients and younger patients are at increased risk of delayed-onset primary CMV disease.

Current concepts on cytomegalovirus infection after liver transplantation

“…In our analysis of 67 CMV D+/R li ver transplant recipients who recei ved 3 mo of oral ganciclovir and valganciclovir prophylaxis, the two year incidence of CMV disease was 29%. The incidence of delayedonset CMV disease was not significantly dif ferent between patients who recei ved oral ganciclovir or valganciclovir (22% vs 28%; P = 0.63) [3] . Thus, one out of every four CMV D+/R li ver transplant recipients will de velop CMV disease after cessation of anti viral prophylaxis.…”

“…The incidence is markedly reduced in li ver transplant recipients who recei ved 3 mo of prophylaxis with valganciclovir or oral ganciclovir. Re cent studies have reported CMV disease incidence rates of 12%30% in CMV D+/R, and < 10% in CMV R+ li ver transplant recipients who recei ved 3 mo of anti viral prophylaxis [3,4,9,1113] . The onset of disease in these patients occurs most commonly during first 3 mo after completing anti viral prophylaxis; hence, the term "delayedonset (also termed lateonset) CMV disease" to indicate that the on set has been delayed by anti viral prophylaxis (Figure 1) [3] .…”

“…Other factors associated with CMV dis ease after li ver transplantation include cold ischemia time, bacterial and fungal infections and sepsis, the amount of blood loss, fulminant hepatic failure as the indication for liver transplantation, age, female gender, Hispanic race, and renal insufficiency [2,3,20,57] .…”

“…Thus, one out of every four CMV D+/R li ver transplant recipients will de velop CMV disease after cessation of anti viral prophylaxis. Delayedonset CMV disease most commonly presented as CMV syndrome, with fever and bone marrow sup pression [3] . In less than half of the patients, CMV mani fested as tissueinvasive disease, and frequently effected the gastrointestinal tract [3] .…”

“…Delayedonset CMV disease most commonly presented as CMV syndrome, with fever and bone marrow sup pression [3] . In less than half of the patients, CMV mani fested as tissueinvasive disease, and frequently effected the gastrointestinal tract [3] . Factors such as age [3] , female gender [3,78] , renal dysfunction [78] , and allograft rejection [13] predisposed to the development of delayedonset primary CMV disease.…”