High-risk Liver Transplant Recipients Research Articles

Universal Prophylaxis With Fluconazole for the Prevention of Early Invasive Fungal Infection in Low-Risk Liver Transplant Recipients

Although antifungal prophylaxis in high-risk liver transplant recipients (LTR) seems to be clearly justified, the efficacy of universal prophylaxis (UP) including low-risk patients is controversial. From the study cohort RESITRA-REIPI, which prospectively analyzed 1010 LTR (September 2003 to February 2005) in 12 Spanish hospitals, we compared the incidence of early invasive fungal infection (IFI, first 90 days) between centers performing or not UP with fluconazole (for a minimum of 7 days) in low-risk LTR (none of the following: posttransplant renal failure, urgent transplant/retransplant, or choledochojejunostomy). Three of 12 centers used UP. A total of 799 LTR were considered as low-risk patients (206 included in the UP group and 593 did not). We reported a total of 11 episodes of early IFI (six due to Candida albicans, one due to C. guillermondii, and three due to Aspergillus fumigatus) in 10 patients (incidence: 1.2%), with two cases of death attributable to IFI (18%) in both patients with invasive aspergillosis. There were no differences in the incidence of IFI between the patients receiving or not UP (4/206:1.9% vs. 6/593:1%, respectively; P=0.36). IFI is infrequent in LTR not fulfilling major high-risk factors criteria, and prophylaxis with fluconazole in this low-risk group does not seem to be justified.

Candidiasis invasora en un receptor de trasplante hepático: tratamiento antifúngico de rescate precoz

Background : Some liver transplant recipients could be at risk for candidemia or invasive candidiasis during the immediate postoperative period after transplantation. Prophylaxis is the best strategy to reduce the incidence of invasive fungal infection caused by Candida species in high-risk liver transplant recipients (HR-LTR), but in cases of suspected breakthrough invasive fungal infection due to Candida, both a rapid diagnosis process and early antifungal treatment are the most important factors impacting on the prognosis. Clinical case We report a case of early rescue treatment with anidulafungin in a HR-LTR with complicated postoperative course. We discuss risk factors, prophylaxis, sensitivity of biomarkers, and characteristics of antifungal management. Conclusions : Early rescue antifungal treatment using candins improves the prognosis in HR-LTR suffering from invasive candidiasis.

Invasive Aspergillosis in Solid Organ Transplant Recipients

This chapter discusses the current status and evolving trends in the epidemiology, risk factors, diagnostic laboratory assays, and the approach to antifungal prophylaxis and treatment of invasive aspergillosis in Solid Organ Transplant (SOT) recipients. Most invasive fungal infections in these high-risk patients occur within the first month posttransplant; the median time to onset of invasive aspergillosis after renal replacement therapy and retransplantation was 13 and 28 days, respectively, in one study. Other factors associated with invasive aspergillosis in liver transplant recipients include transplantation for fulminate hepatic failure, cytomegalovirus (CMV) infection, and prolonged intensive care unit stay. A retrospective survey documented invasive pulmonary aspergillosis in 7.5% (19/251) of lung transplant recipients, of whom 47% (9/19) had disseminated aspergillosis. In a survey of antifungal prophylactic strategies in lung transplant units in the United States, aerosolized amphotericin B was the most frequently employed antifungal prophylactic agent. In order of preference, the prophylactic agents used in lung transplant centers in this study were inhaled amphotericin B (61%), itraconazole (46%), parenteral amphotericin formulations (25%), and fluconazole (21%); many centers used more than one agent. Preemptive therapy, where antifungal prophylaxis is directed towards lung transplant recipients colonized with Aspergillus spp. immediately before or within 6 to 9 months after transplantation, is another approach to the prevention of invasive aspergillosis in lung transplant recipients.

Increased incidence of cytomegalovirus infection in high-risk liver transplant recipients receiving valganciclovir prophylaxis versus ganciclovir prophylaxis

Optimal measures for the prevention of cytomegalovirus (CMV) in high-risk orthotopic liver transplant (OLT) patients are unknown. The charts of high-risk OLT recipients with 12 months of follow-up who were transplanted over a 44-month period were reviewed. The incidence of CMV disease in CMV-seropositive donor/CMV-seronegative recipient patients receiving valganciclovir or ganciclovir prophylaxis was compared. Sixty-six patients met the inclusion criteria and were treated with 1 of 3 prophylactic regimens: valganciclovir (900 mg daily; 27 patients), oral ganciclovir (1000 mg every 8 hours; 17 patients), or intravenous ganciclovir (6 mg/kg daily; 22 patients). Eight CMV cases occurred, all after completion of the prophylaxis. The combined incidence of CMV disease with intravenous and oral ganciclovir was lower than the incidence in valganciclovir recipients (P = 0.056; relative risk, 4.33; 95% confidence interval, 0.94-19.87). CMV disease occurred in 22.2% of valganciclovir recipients, 4.5% of intravenous ganciclovir recipients, and 5.9% of oral ganciclovir recipients. In conclusion, late-onset CMV disease occurred more frequently among high-risk liver transplant recipients treated with valganciclovir prophylaxis. The 4-fold higher incidence of CMV disease in our study supports the avoidance of valganciclovir for prophylaxis in high-risk OLT patients. Liver Transpl 15:963-967, 2009. (c) 2009 AASLD.

Prophylaxis With Caspofungin for Invasive Fungal Infections in High-Risk Liver Transplant Recipients

The aim of this prospective, multicenter, noncomparative, open-label trial was to evaluate the prophylactic use of caspofungin in adult liver transplant recipients at high risk of developing invasive fungal infections (IFI). Patients received caspofungin for at least 21 days. A successful treatment outcome was defined as the absence of breakthrough IFI during the first 100 days after the onset of caspofungin. According to study design, 71 patients were included. In the modified intention-to-treat analysis, successful treatment outcome was obtained in 88.7%. Two patients developed IFI: a Mucor and a Candida albicans surgical wound infections, respectively. Six more patients discontinued caspofungin because of drug-related altered liver function. No clinical side effects were related to caspofungin. Altered analytical data compatible with grade IV toxicity, irrespective of caspofungin attribution, were observed in 27.7% of patients at the end of caspofungin prophylaxis and in 15.4% of patients in safety visit (14 days after ending caspofungin administration) (P=0.13). Eight patients died, six during caspofungin administration and two during follow-up period, but none were attributed to IFI or caspofungin toxicity. These results show that caspofungin could be considered an efficacious and well-tolerated drug as antifungal prophylaxis in high-risk liver transplant recipients.

Splenic artery occlusion for small-for-size syndrome: Better late than never but early is the best

Splenic artery occlusion for small-for-size syndrome: Better late than never but early is the best

Outcomes of antifungal prophylaxis in high‐risk liver transplant recipients

Antifungal prophylaxis for liver transplant recipients (LTRs) is common among patients considered at high risk of infection, but optimal prophylaxis duration and drug has not been defined. This study aimed to assess the effects of 14 days of antifungal therapy prophylaxis in reducing proven invasive fungal infections (IFI) in high-risk subjects. Eligible subjects who met 2 or more risk criteria were randomized 1:1 to the treatment arms (liposomal amphotericin B or fluconazole) and were followed for 100 days post transplantation for evidence of IFI. The study was designed to enroll 300 subjects, but was closed early for insufficient enrollment. A total of 71 subjects were enrolled and randomized. Two-thirds of subjects completed 14 days of study therapy. Ten subjects developed proven or probable IFI with Candida species (9 subjects) and Cryptococcus neoformans (1 subject); rates were similar in the 2 treatment arms. Eleven subjects died, but no death was attributed to study drug or IFI. In summary, high-risk LTRs tolerated antifungal prophylaxis well, and rates of IFI were lower than previously reported in untreated high-risk LTRs.

Dysregulated expression of T-helper cell responses and susceptibility to infections in high-risk liver transplant recipients

Background Liver transplant recipients requiring dialysis have poor outcomes including higher risk of infection, and allograft rejection. The role of T-helper cell cytokine responses in the pathogenesis of infections in these patients has not been fully defined. Methods Cases were 11 dialyzed liver transplant recipients. Controls (2 for each case) were patients who were transplanted next to the case but did not require dialysis at any time before or after transplantation. Cytokine responses were assessed in sera collected immediately before transplantation. Data were analyzed for candidate cytokines for pro-inflammatory Th1 (IL-1β, IL-12p70, and IFN-γ), and Th17 (IL-12p40, IL-17), and anti-inflammatory Th2 phenotypes (IL-4, IL-5, IL-10, and IL-13). Results Cases were more likely to have an increase in any of the Th1 or Th1 and Th17 cytokines than the controls ( p = 0.016 and p = 0.04, respectively). Major infections developed in 27% of the study population; these included 46% of the cases and18%, of the controls ( p = 0.09). Patients with infections vs. those without these were more likely to have an increase in any of the Th2 cytokines ( p = 0.005). CMV viremia occurred in 30% of the patients and was significantly associated with Th1 responses even when adjusted for CMV recipient/donor serostatus or any major infection (OR 3.2, 95% CI 0.96–10.73, p = 0.05). Conclusions Requirement of dialysis was characterized by a state of heightened expression of inflammatory responses. However, patients developing infections preferentially expressed Th2 phenotype that may act as a negative regulator of protective inflammatory responses. An enhanced expression of inflammatory mediators may serve to promote CMV infection in liver transplant recipients.

Reply: Effect of prophylaxis on fungal infection and costs for high-risk liver transplant recipients

to determine the efficacy of pro-phylactic amphotericin B (AMPH) in high-risk livertransplantrecipients.Intheirstudy,fungiwereisolatedfrom 37 anatomic sites in 31 patients defined to havefungal infections (28 in the no-prophylaxis group and 3in the AMPH group). The authors concluded that “fail-ure to offer prophylaxis conferred a 4-fold greater risk offungal infection.” However, their definition of fungalinfection may have overestimated the number of truefungal infections (particularly in the no-prophylaxisgroup) by potentially using the isolation of

Avoiding calcineurin inhibitors in the early post‐operative course in high‐risk liver transplant recipients: The role of extracorporeal photopheresis

The aim of this work is to report on the results of a single-center, prospective study on the feasibility of calcineurin-inhibitor (CNI)-staggered immunosuppression by use of extracorporeal photopheresis (ECP) in liver transplant (LT) recipients at risk of renal and neurological complications. Patients were matched on a 1:1 basis with historical controls on standard CNI immunosuppression. ECP patients were treated with ECP plus antimetabolites and/or steroids, while CNIs were withheld until clinically indicated. Thirty-six patients were evaluated: 18 ECP patients and 18 controls. ECP was tolerated in 100% of cases. CNI were introduced at a median of 8 days (4-55) in 17 ECP patients, while one patient was on a fully CNI-sparing regimen 22 months after LT. Acute rejection occurred in 27.7% patients in ECP (5/18) versus 16.7% in controls (3/18) (P = ns) with a shorter time to rejection in ECP (36 +/- 31.3 days vs. 83.6 +/- 65.6 days; P = ns). All rejection episodes were amenable to medical treatment. Neurological and renal complications occurred in 22.2% (4/18) of patients in either group, but led to in-hospital mortality in 3 patients among controls versus 1 in ECP (P = ns). One-, 6-, and 12-month survival rates were 94.4, 88.1, and 88.1% in ECP versus 94.4, 77.7, and 72.2% among controls (P < 0.0001). ECP seems to allow for management of high-risk LT recipients in the early post-transplant course and reduction of CNI-related mortality. Continued data validation is favored to assess the impact of ECP on long-term graft and patient survival.

Effect of prophylaxis on fungal infection and costs for high-risk liver transplant recipients

We sought to determine whether the prophylactic use of amphotericin B products (conventional amphotericin B and liposomal amphotericin B) reduces the incidence of fungal infections in high-risk liver transplant recipients, and if so, whether this lowers the cost of care. The study sample comprised 232 adult orthotopic liver transplants performed from 1994 to 2005 at a single center for patients classified as being at high risk for fungal infections. High-risk patients who received transplants with a prophylaxis regimen of amphotericin B (n=58 transplants) were compared with high-risk patients who received no prophylaxis (n=174 transplants). Fungal infections occurred in 3 transplants (5.17%) of those who received amphotericin B and 28 transplants (16.09%) in those without prophylaxis (P=0.0432). Regression models were used to analyze fungal infection and costs for the 232 high-risk transplants. Failure to offer prophylaxis conferred a 4-fold greater risk of fungal infection (P=0.046) compared with those who received amphotericin B. A fungal infection in a high-risk recipient increased mean costs by 46.48%. The indirect effect of prophylaxis (operating through infection reduction) is estimated to reduce overall costs in high-risk patients by 8.73%.

Question of using valganciclovir for cytomegalovirus (CMV) infection prophylaxis in post–liver transplant recipients

We read the article by Park et al. with great interest.1 The authors retrospectively studied the efficacy of low-dose oral valganciclovir (n = 49) compared with the standard dose of ganciclovir (n = 60) for the prevention of cytomegalovirus (CMV) disease in adult liver transplant recipients. The authors found 2 patients in each group with CMV disease within 1 year of follow-up. Both patients in the ganciclovir group were high risk for CMV (donor positive, recipient negative), while in valganciclovir group, 1 patient was high-risk and 1 was low risk.1 Absorption of valganciclovir has been found to be 10 times higher than oral ganciclovir, with bioavailability of nearly 60% in healthy volunteers and in patients who are human immunodeficiency virus positive with CMV. Based on these findings, we agree that the greater absorption and antiviral activity of valganciclovir offers an attractive option for prophylaxis against CMV after solid-organ transplantation.2-4 However, when we analyzed 203 consecutive post–liver transplant recipients treated with prophylactic valganciclovir between July 2001 and May 2003, we found an overall rate of 17% symptomatic CMV, when either the donor or the recipient was exposed to CMV. It was 25.9% in the high-risk group, (donor positive, recipient negative, based on CMV serology). Some of the patients developed CMV even while on valganciclovir prophylaxis.5, 6 Since our publication, we have screened more high-risk recipients for CMV during and after valganciclovir prophylaxis and have found a higher rate than the rate published earlier. In concurrence with our findings, a double-blind, prospective trial was conducted by Roche laboratories (manufacturers of valganciclovir and ganciclovir) in 372 posttransplantation patients with high risk for CMV disease (heart, n = 56; liver, n = 177; kidney, n = 120; and kidney/pancreas, n = 11) comparing valganciclovir and ganciclovir prophylaxis. The overall results at 6 months suggested that the rate of CMV disease (including invasive CMV) was 12.1% with valganciclovir prophylaxis compared to 15.2% with ganciclovir. However, in liver transplant recipients, the rate of invasive CMV disease was 12% in the valganciclovir group compared to 3% in oral ganciclovir group. Based on these findings, valganciclovir was not recommended for CMV prophylaxis in high-risk liver transplant recipients.7 One fails to understand why liver transplant recipients had higher rates of CMV compared to kidney or heart transplant recipients under valganciclovir prophylaxis. Both mycophenolate mofetil and valganciclovir require esterase to convert them into active forms (mycophenolic acid and ganciclovir, respectively). Post–liver transplant recipients often have initial hepatic and/or bowel dysfunction, and therefore the enzyme may be quantitatively deficient or qualitatively ineffective. Improved absorption of valganciclovir over time has been reported in liver transplant recipients. Also, valganciclovir could be competing with mycophenolate mofetil for esterase to be converted to active ganciclovir. Previous pharmacokinetic studies on valganciclovir were performed 21 to 180 days after liver transplant.2-4 There is a lack of pharmacokinetic data in the early post–transplant period. In the present report, it is possible that the authors might have found a lower rate of CMV because not all patients were screened for CMV disease after discontinuation of prophylaxis. In addition, because of the retrospective nature of the study, some patients might have been missed, as some patients might not have presented to their clinic or might not have been documented adequately. It is particularly important to note that the overall rate of CMV disease was only 4% in the entire group,1 much lower than that observed by others. We feel that the findings of this retrospective study, which indicates that valganciclovir provides adequate prophylaxis for liver transplant recipients, should be treated with caution in clinical practice until more prospective clinical trials are conducted. It is important to have a high degree of suspicion for CMV infection during and, particularly, after discontinuation of valganciclovir prophylaxis. Ashok Jain*, Ravi Mohanka*, Mark Orloff*, Peter Abt*, Charlotte Ryan , Adel Bozorgzadeh*, * Department of Surgery, Division of Transplantation, University of Rochester Medical Center, Rochester, NY, Department of Pathology, University of Rochester Medical Center, Rochester, NY.

Prospective Interventional Study to Evaluate the Efficacy and Safety of Liposomal Amphotericin B as Prophylaxis of Fungal Infections in High-Risk Liver Transplant Recipients

Introduction Invasive fungal infections are a life-threatening complication in transplant recipients. The prevalence of fungal infection after orthotopic liver transplantation (OLT) is 5% to 42%. The most common isolated pathogens are Candida and Aspergillus species. High-risk liver transplant recipients are more susceptible to the development of invasive fungal infections, with prevalence >40% and mortality rates of 78% to 100%. The strategy for fungal prophylaxis in this population has not been defined. Patients and methods Among 100 consecutive OLT followed for 28 months, 21 recipients (15 men, overall mean age of 48.5 years, range 23–65 years) were considered to be high risk for the development of fungal infections when they presented at least one of the following criteria: acute liver failure, assisted ventilation >7 days, retransplantation, relaparotomy, antibiotic therapy >14 days, transfusion requirements >20 red blood cells units, and/or biliary leakage. This group received intravenous liposomal amphotericin B (1 mg/kg/d for 7–10 days). Results One-year survival in the high-risk group was 80%. Prevalence of invasive fungal infection was 9.5%. No Candida infection was observed. Two patients developed Aspergillus infection: an abdominal aspergillosis treated with percutaneous drainage and liposomal amphotericin B (5 mg/kg/d) showed a favorable clinical outcome. The other patient who developed brain aspergillosis died 25 days after OLT. Adverse events related to the drug were hypokalemia (n = 2), back pain (n = 3), and renal dysfunction (n = 2). None of these events required withdrawal of the prophylaxis regimen. Conclusion In our series, prophylaxis with liposomal amphotericin B in high-risk liver graft recipients showed a low rate of severe fungal infections. More studies are needed in order to determine the highest risk population and the best drug dosage.

Low‐dose amphotericin for prevention of serious fungal infection following liver transplantation

This study advances previously performed clinical studies of antifungal prophylaxis and prospectively evaluates the efficacy of low-dose amphotericin B preparations for the prevention of invasive fungal infection (IFI) in high-risk liver transplant (LT) recipients. High-risk LT patients were recruited and randomised to openly receive intravenously either conventional amphotericin B (amB) at a dose of 15 mg daily, or liposomal amphotericin B (amBisome) 50 mg daily. Prophylaxis was continued until discharge from the intensive care unit (ICU), until patient death, or until time of conversion to high-dose amBisome for treatment of suspected or confirmed IFI. During the study period, 360 adult LTs were performed; 132 patients were eligible for 149 recruitment episodes into the trial, and 83 patients were recruited for 92 episodes. Of the 92, 48 patient episodes were randomised to receive amBisome prophylaxis, and 44 to receive amB. IFI was uncommon, diagnosed for 3 patients in the amBisome group, and for 2 in the amB group. Furthermore, Aspergillus was isolated on a single occasion during 92 episodes of prophylaxis. Fungal colonisation scores did not differ significantly between the 2 groups. There was a significant difference in the rates of survival to ICU discharge between the 2 groups (79.6% amBisome vs. 59.5% amB, P=0.038). Renal function measures including creatinine clearance at commencement and conclusion of prophylaxis, and at 12 months post transplant were not statistically different between the 2 groups. The use of amphotericin B, liposomal or non-liposomal preparations at low doses, for prophylaxis of IFI in high-risk LT patients, is associated with a low incidence of serious fungal infection. In this randomised study, low-dose amBisome prophylaxis was associated with an increased likelihood of successful discharge from the ICU.

Independent risk factors and natural history of renal dysfunction in liver transplant recipients

Renal dysfunction is common after liver transplantation. However, there are only limited data on the predictors and natural history of renal dysfunction after liver transplantation. In this study, we determined independent predictors and the natural history of renal dysfunction in 172 consecutive liver transplant recipients. Survival and time to development of permanent renal dysfunction (renal dysfunction defined as a sustained decrease in estimated glomerular filtration rate (GFR) of > 30 mL/min/1.73 m 2 from baseline for at least 6 months, severe renal failure defined as absolute GFR <30 mL/min/1.73 m 2 for at least 6 months) were determined using the Kaplan-Meier method. Cox regression analysis was used to test the independent effect of a given set of variables on time to development of such an event. Nine percent of patients required immediate dialysis, 35% developed permanent renal dysfunction, and 7% developed severe renal failure. The rate of decline in renal dysfunction was maximal, 6.5 mL/min/1.73 m 2 /mo, at 1 month after liver transplantation. Pre-existing diabetes mellitus, major surgical infection, and waiting time on the transplant list were independent risk factors for immediate dialysis. Presence of serum creatinine > 1.2 mg/dL at any time before liver transplantation and a baseline GFR <70 mL/min/1.73 m 2 were independent predictors of permanent renal dysfunction. Diabetes mellitus, coronary artery disease, and primary graft nonfunction predicted the development of severe renal failure. GFR stabilized around 9 months, and presence of decreased GFR > 30mL/min/1.73 m 2 from baseline at 9 months predicted development of permanent renal dysfunction. An absolute GFR of <30mL/min/1.73 m 2 occurring as early as 3 months after liver transplantation predicted severe renal failure. Severe renal failure was associated with a significantly lower survival by Cox regression analysis. We have identified risk factors and the natural history of permanent renal dysfunction and severe liver failure in liver transplant recipients. These observations may be useful in the development of nonnephrotoxic immunosuppressive regimens for high-risk liver transplant recipients. ( Liver Transpl 2003;9:741-747.)

Prevention and treatment of epstein–barr virus‐associated lymphoproliferative disorders in recipients of bone marrow and solid organ transplants

Prevention and treatment of epstein–barr virus‐associated lymphoproliferative disorders in recipients of bone marrow and solid organ transplants

Research agenda for pediatric gastroenterology, hepatology and nutrition: transplantation. Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the Children's Digestive Health and Nutrition Foundation.

Research agenda for pediatric gastroenterology, hepatology and nutrition: transplantation. Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the Children's Digestive Health and Nutrition Foundation.

Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requiring renal replacement therapy.

Posttransplant renal replacement therapy has been shown to be an independently significant risk factor for invasive fungal infections after liver transplantation. We assessed the efficacy of a lipid preparation of amphotericin B as prophylaxis for invasive fungal infections, directed toward liver transplant recipients requiring renal replacement therapy. A total of 148 patients transplanted between 1990 and 1997 received no antifungal prophylaxis. Since 1997, 38 patients underwent liver transplantation; antifungal prophylaxis with a lipid preparation of amphotericin B was used in patients requiring renal replacement therapy. Fifteen percent (22 of 148) of the patients transplanted before 1997 required renal replacement therapy. In this cohort, the incidence of invasive fungal infections (36% vs. 7%, P=0.0007) and invasive aspergillosis (14% vs. 2%, P=0.02) was significantly higher in patients who required renal replacement therapy compared with those who did not. Since 1997, 29% (11 of 38) of the patients required renal replacement therapy and received antifungal prophylaxis. Invasive fungal infections occurred in 36% (8 of 22) of the patients who received no prophylaxis (patients before 1997), and 0% (0 of 11, P=0.03) in those who received antifungal prophylaxis (since 1997). Antifungal prophylaxis was independently associated with protection from fungal infection (P=0.017). No reduction in mortality with antifungal prophylaxis was documented. Prophylaxis with a lipid preparation of amphotericin B was associated with a significant reduction in invasive fungal infections in high-risk liver transplant recipients, i.e., those requiring renal replacement therapy. However, no beneficial effect on survival could be documented.

Prophylactic antifungal therapy in the intensive care unit.

Antifungal prophylaxis is regularly used during treatment of patients with some cancers, as subgroups with high rates of invasive fungal infections are readily identified; for these patients, prophylaxis has been shown to be of value. High-risk liver transplant recipients also benefit from antifungal prophylaxis. Although the idea of extending this concept to the prevention of candidal infections in the larger population of critically ill patients who are seen in the intensive care unit (ICU) and who do not have neutropenia is attractive, implementation of this strategy is difficult because of the widely varying characteristics of patients in the ICU. Two studies have shown the benefit of such prophylaxis, but the benefit was shown only in selected groups of patients who had an unusually high risk for invasive candidiasis. Although the concept is sound, broad-scale implementation of antifungal prophylaxis would be premature and costly, both financially and with regard to resistance and toxicity. Investigations are needed to define and prove the utility of predictive tools for the identification of patients in the ICU who would benefit from prophylaxis.

Prophylactic antiviral therapy in CMV high-risk liver transplant recipients

Prophylactic antiviral therapy in CMV high-risk liver transplant recipients