Search

Background Elevated serum iron levels have been associated with infectious outcomes in various patient populations but, to our knowledge, have never been studied after liver transplantation. Methods The relationship between serum iron levels and infectious outcomes after liver transplantation was evaluated in a nested case-control study using prospectively collected data and serum samples. Unadjusted and adjusted hazard ratios were calculated for each iron marker predictor variable (iron level, unsaturated iron-binding capacity, total iron-binding capacity, transferrin saturation, and ferritin level) and time to development of each of 6 outcomes (cytomegalovirus [CMV] disease, invasive fungal infection, bacteremia, invasive fungal infection or bacteremia, any infection, and 1-year mortality rate). Results Serum measurements (n = 109) corresponding to increased levels of serum iron were independently associated with an increased risk of any infection and death. After adjusting for the number of red blood cell transfusions, donor CMV-seropositive status, and fungal colonization, ferritin level was independently associated with the development of any infection (hazard ratio, 1.09; 95% confidence interval, 1.04-1.14). After adjusting for the number of red blood cell transfusions, development of CMV disease, and administration of intravenous steroids for treatment of rejection, ferritin level was also was independently associated with death (hazard ratio, 1.11; 95% confidence interval, 1.04-1.18). Similar results were found for unsaturated iron binding capacity for the same 2 outcomes. Conclusions A better understanding of iron metabolism and its relationship to infection could help guide future infection prognosis, prevention, and management efforts in this high-risk population. more...

Predictors of recurrent cytomegalovirus (CMV) disease after the first episode of successfully treated CMV disease in orthotopic liver transplant recipients were studied. Recurrent CMV disease was defined as disease diagnosed > 14 days after the end of a minimum 8-day course of ganciclovir therapy for the first episode and was classified as early or late if it occurred within or after 90 days, respectively, after completion of ganciclovir treatment. Eleven (27%) of 41 patients had recurrent CMV disease (nine early recurrences and two late recurrences). Death was more likely to occur in patients with recurrent CMV disease than in those without it (55% vs. 13%, respectively; P = .006). Initial episodes of multiorgan CMV disease (P = .001) and CMV pneumonia (P = .012) were associated with early recurrence. Multivariate analysis showed that multiorgan CMV disease was independently associated with early recurrence (P = .003; odds ratio, 13.5; 95% confidence interval, 2.4-76.8). Recognition of risk factors for recurrent CMV disease may help identify patients for whom a more intensive therapeutic or diagnostic approach is needed. more...

The role of markers of cytomegalovirus (CMV) infection, such as the isolation of CMV, the presence of CMV antigenemia, or detection of viral DNA by polymerase chain reaction (PCR) assay, as predictors of subsequent CMV disease has been examined in recent studies. We studied the value of performing surveillance cultures of blood, urine, and throat specimens in a cohort of 156 liver transplant recipients who had participated in clinical trials and had received ganciclovir only for documented CMV disease. Cultures of urine and throat specimens for detection of CMV were performed every week, and cultures of blood specimens were performed every other week for the first 2 months after transplantation, then monthly for 6 months. Eighty-nine (57%) of 156 patients developed CMV infection, 41 (46%) of whom developed clinical CMV disease (36 had organ involvement and five had CMV syndrome). Fifty (32%) of 156 patients had positive blood cultures, 35 (22%) had positive urine cultures, and 41 (26%) had positive throat cultures. The positive and negative predictive values of surveillance cultures for predicting CMV disease were as follows: blood cultures, 46% and 83%, respectively; urine cultures, 26% and 74%, respectively; and throat cultures, 32% and 76%, respectively. These data indicate that such cultures are not useful in predicting CMV disease in liver transplant recipients. Future studies should examine the value of alternative markers, such as CMV antigenemia or the detection of viral DNA by PCR, for predicting CMV disease in this setting. more...

To define predictors of bacteremia and to assess the potential role of exposure to cytomegalovirus (CMV) as a risk factor for bacteremia in liver transplant recipients, an intention-to-treat analysis of data for 146 orthotopic liver transplant recipients who participated in a multicenter, randomized, intervention trial was undertaken. Fifty-eight episodes of bacteremia occurred in 40 (27.4%) of 146 patients within 1 year after transplantation. Bacteremia was diagnosed a median of 39.5 days (range, 1-325 days) after transplantation. One-year mortality rates were higher among patients with bacteremia than among those without bacteremia (47.5% [19 of 40] vs. 18% [19 of 106], respectively; P = .001). A time-dependent multivariate analysis of variables that were significantly (P < or = .05) associated with bacteremia in the univariate analysis showed that donor CMV seropositivity (relative risk [RR], 3.4; 95% confidence interval [CI], 1.6-6.6; P = .0005), age of younger than 16 years (RR, 2.6; 95% CI, 1.3-5.2; P < .0059), and a major abdominal operation after transplantation excluding retransplantation (RR, 3.8; 95% CI, 1.8-8.0; P = .0004) were independently associated with bacteremia. These epidemiologic data suggest that exposure to CMV from the donated organ is an independent risk factor for bacteremia in orthotopic liver transplant recipients. more...

Primary cytomegalovirus (CMV) infection in liver transplant recipients generally occurs following transmission via a CMV-seropositive donor organ. Occasionally primary infection arises in recipients of CMV-seronegative donor organs through blood transfusions. We studied the differences in clinical manifestations of primary CMV infection associated with these two modes of transmission, among 40 liver transplant recipients who had documented primary CMV infection post-transplantation. Thirty-one of 40 patients received a CMV-seropositive donor organ; CMV infection in the other nine patients was transfusion related. Symptomatic CMV disease (22 of 31 vs. 4 of 9; P = .06), CMV hepatitis (20 of 31 vs. 1 of 9; P = .007), invasive fungal disease (13 of 31 vs. 0 of 9; P = .03), and death (16 of 31 vs. 1 of 9; P = .06) were more likely to occur in patients with donor organ-associated primary CMV infection. The incubation period between transplantation and onset of CMV infection, a possible marker for viral load, was shorter in recipients of donor organ-transmitted CMV infection (median, 44 vs. 137 days; P = .004). Controlling for potential confounders such as immunosuppression did not alter these associations. Primary CMV infection associated with the donor organ has a more profound impact than primary infection associated with transfusion. These differences may be due to dissimilarities in the viral load associated with donated livers and transfused blood products. more...