Plasmapheresis and Intravenous Immune Globulin Improve Neurologic Outcome of Central Pontine Myelinolysis Occurring Post Orthotopic Liver Transplant.

OBJECTIVE: To report 2 cases of central pontine myelinolysis (CPM) post liver transplantation in which treatment with plasmapheresis and intravenous immune globulin improved expected neurologic outcome. CASE SUMMARY: Two patients who underwent orthotopic liver transplant developed CPM early in their postoperative course. Magnetic resonance imaging of the brain demonstrated severe demyelination of either the pons or the midbrain, respectively. Both patients developed significant neurologic abnormalities, including acute mental status changes, severe muscle weakness, spasticity, and/or prolonged paralysis. Pretransplant laboratory results indicated serum sodium levels fluctuating between 115 mEq/L and 152 mEq/L. Both patients received 6 days of plasmapheresis (PP) followed by 5 consecutive days of intravenous immune globulin (IVIG). Significant neurologic improvement was experienced at 2 and 4 weeks, respectively, after therapy was initiated. Complete resolution of neurologic symptoms was evident at 1 year follow-up. DISCUSSION: Currently, specific guidelines or recommendations for the treatment of CPM are practically nonexistent. CPM remains a neurologic complication that is difficult to treat and may result in permanent significant neurologic sequelae. The etiology and pathogenesis of this disease are unclear, although aggressive osmolar correction, particularly in the setting of hyponatremia, is the main risk factor. While patients may eventually show some improvement with supportive care, progress is often protracted, and complete resolution of symptoms is exceedingly rare. The severity of the midbrain lesions juxtaposed against the rapidity of symptom resolution in these 2 patients alludes to a potential therapeutic benefit after initiation of therapy with PP and IVIG. CONCLUSIONS: These cases suggest that prompt recognition of CPM and initiation of PP and IVIG may help modulate its progress and improve long-term neurologic outcome.

A real-time, telemetric method for continuous measurement of portal pressures.

The ability to longitudinally monitor portal and splanchnic pressures would greatly enhance the understanding of acute and chronic liver disease by helping to assess the immediate and long-term impact of therapeutic manipulations. However, a technique for measuring portal pressures in the ambulatory setting is not currently available. To overcome this difficulty, we utilized an approach that involved the implantation of a miniature telemetric device, equipped with a specially-designed pressure transmission catheter, into the spleen of an anesthetized mouse. Using this approach, portal pressures were measured continuously over 5 d in conscious, unrestrained animals, the availability of which will help facilitate studies of the portal circulation requiring long-term stability.

Liver transplantation for cholangiocarcinoma.

Liver transplantation for cholangiocarcinoma (CCA) remains a controversial subject. More than 15 years after, a novel protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation was first used in patients with unresectable hilar CCAs, these methods have yet to reach broad application. Results have confirmed that this approach leads to significantly lower recurrence rates and higher long-term survival rates than other existing treatment modalities. Despite this, protocols to treat patients with CCA are not widespread, and are available at only a handful of transplant programs. At these centers, treatment success may ultimately hinge on regional model for end-stage liver disease scores and waiting time for transplant. While acknowledging these factors as well as a severe organ shortage, it is important that the transplant community not overlook a potentially effective form of therapy for a previously untreatable disease.

The hepatoadrenal syndrome: a common yet unrecognized clinical condition.

OBJECTIVE: Adrenal failure is common in critically ill patients, particularly those with sepsis. As liver failure and sepsis are both associated with increased circulating levels of endotoxin and proinflammatory mediators and reduced levels of apoprotein-1/high-density lipoprotein, we postulated that adrenal failure may be common in patients with liver disease. DESIGN: Clinical study. SETTING: Liver transplant intensive care unit. PATIENTS: The study cohort included 340 patients with liver disease. INTERVENTIONS: Based on preliminary observational data, all patients admitted to our 28-bed liver transplant intensive care unit (LTICU) undergo adrenal function testing. An honest broker system was used to extract clinical, hemodynamic, medication, and laboratory data on patients admitted to the LTICU from March 2002 to March 2004. A random (stress) cortisol level <20 microg/dL in a highly stressed patient (respiratory failure, hypotension) was used to diagnose adrenal insufficiency. In all other patients, a random cortisol level <15 microg/dL or a 30-min level <20 microg/dL post-low-dose (1 microg) cosyntropin was considered diagnostic of adrenal insufficiency. Patients were grouped as follows: a) chronic liver failure; b) fulminant hepatic failure; c) patients immediately status post-orthotopic liver transplantation receiving a steroid-free protocol of immunosuppression; and d) patients status post-remote liver transplant (>/=6 months). The decision to treat patients with stress doses of hydrocortisone was at the discretion of the treating intensivist and transplant surgeon. MEASUREMENTS AND MAIN RESULTS: Two-hundred and forty-five (72%) patients met our criteria for adrenal insufficiency (the hepatoadrenal syndrome). Eight (33%) patients with fulminant hepatic failure, 97 (66%) patients with chronic liver disease, 31(61%) patients with a remote history of liver transplantation, and 109 (92%) patients who had undergone liver transplantation under steroid-free immunosuppression were diagnosed with adrenal insufficiency. The high-density lipoprotein level at the time of adrenal testing was the only variable predictive of adrenal insufficiency (p < .0001). In vasopressor-dependent patients with adrenal insufficiency, treatment with hydrocortisone was associated with a significant reduction (p = .02) in the dose of norepinephrine at 24 hrs, whereas the dose of norepinephrine was significantly higher (p = .04) in those patients with adrenal failure not treated with hydrocortisone. In vasopressor-dependent patients without adrenal insufficiency, treatment with hydrocortisone did not affect vasopressor dose at 24 hrs. One hundred and forty-one patients (26.4%) died during their hospitalization. The baseline serum cortisol was 18.8 +/- 16.2 microg/dL in the nonsurvivors compared with 13.0 +/- 11.8 microg/dL in the survivors (p < .001). Of those patients with adrenal failure who were treated with glucocorticoids, the mortality rate was 26% compared with 46% (p = .002) in those who were not treated. In those patients receiving vasopressor agents at the time of adrenal testing, the baseline cortisol was 10.0 +/- 4.8 microg/dL in those with adrenal insufficiency compared with 35.6 +/- 21.2 microg/dL in those with normal adrenal function. Vasopressor-dependent patients who did not have adrenal failure had a mortality rate of 75%. CONCLUSIONS: Patients with liver failure and patients post-liver transplantation have an exceedingly high incidence of adrenal failure, which may be pathophysiologically related to low levels of high-density lipoprotein. Treatment of patients with adrenal failure may improve outcome. High baseline serum cortisol levels may be a maker of disease severity and portend a poor prognosis.

Indirect outcomes associated with cytomegalovirus (opportunistic infections, hepatitis C virus sequelae, and mortality) in liver-transplant recipients with the use of preemptive therapy for 13 years.

BACKGROUND: The effect of preemptive therapy on indirect sequelae associated with cytomegalovirus (CMV) in liver-transplant recipients has not been clearly delineated. METHODS: Thirteen years of outcome with the use of preemptive therapy were assessed in a cohort of 216 consecutive liver-transplant recipients. RESULTS: The incidence of major infections (31% vs. 44.3%), bacterial infections (31% vs. 39.2%), bacteremia (19% vs. 29.1%), or fungal infections (3.4% vs. 7.6%) did not differ significantly for patients with CMV infection who received preemptive therapy compared with those who never developed CMV infection and did not receive antiviral prophylaxis for CMV (P>0.20 for all variables). The rate of opportunistic infections also did not differ when patients were stratified by primary CMV infection, reactivation infection, or no CMV infection. Recurrent hepatitis C virus (HCV) hepatitis occurred in 55.6% of the patients with CMV treated with preemptive therapy and 49.8% of those without CMV infection (P>0.20). The probability of survival at 6 months, 12 months, 2 years, and 3 years was also comparable for the two groups. CONCLUSIONS: Liver-transplant recipients with CMV infection, including high-risk R-/D+ patients, when followed using the preemptive therapy approach had no significant difference in meaningful outcomes such as opportunistic superinfections, HCV recurrence rates, rejection, and survival when compared with the patients in whom CMV infection never developed and who did not receive antiviral prophylaxis for CMV.

Efficacy of valganciclovir administered as preemptive therapy for cytomegalovirus disease in liver transplant recipients: impact on viral load and late-onset cytomegalovirus disease.

BACKGROUND: The efficacy of valganciclovir used as preemptive therapy for cytomegalovirus (CMV) disease in liver transplant recipients is not known. METHODS: Between 1996 and 2004, surveillance testing using CMV antigenemia was performed at weeks 2, 4, 6, 8, 10, 12, and 16 posttransplant. A total of 28.8% (17/59) of the patients from 2001 to 2004 with antigenemia who received valganciclovir as preemptive therapy were compared with 26.2% (21/80) of the patients from 1996 to 2000 who received oral ganciclovir as preemptive therapy. RESULTS: The mean decline in the antigenemia level after initiation of valganciclovir and oral ganciclovir was 80.5% versus 50.7% at 1 week, 99.5% versus 89.4% at 2 weeks, and 100% versus 97.7% at 4 weeks, respectively. A higher proportion of patients who received valganciclovir (64.7%) belonged to the high-risk group (R-/D+) than patients who received oral ganciclovir (33.3%, P=0.10). Recurrent shedding was documented in 47.1% (8/17) of the patients in the valganciclovir group and 28.6% (6/21) of the patients in the oral ganciclovir group (P>0.20). Recurrent shedding correlated significantly with R-/D+ CMV serostatus and baseline CMV antigenemia level, regardless of the study group. No patient in either group developed CMV disease during or after the period of surveillance monitoring. The incidence of opportunistic infections and patient outcome did not differ for the valganciclovir group versus the oral ganciclovir group or patients without CMV infection (P>0.20). CONCLUSION: Antigenemia-directed valganciclovir as preemptive therapy seems to be effective for the prevention of CMV disease in liver transplant recipients, including high-risk patients.

Use of alemtuzumab and tacrolimus monotherapy for cadaveric liver transplantation: with particular reference to hepatitis C virus.

We have proposed that the mechanisms of alloengraftment and variable acquired tolerance can be facilitated by minimum posttransplant immunosuppression. It was further suggested that the efficacy of minimalistic treatment could be enhanced by preoperative recipient conditioning with an antilymphoid antibody preparation. A total of 76 adults (38 hepatitis C virus [HCV], 38 HCV) were infused with 30 mg alemtuzumab before primary cadaveric liver transplantation and maintained afterward on daily monotherapy unless breakthrough rejection mandated additional agents. In stable patients, the intervals between tacrolimus doses were lengthened ("spaced weaning") after approximately 4 months. Eighty-four contemporaneous nonlymphoid-depleted liver recipients (58 HCV, 26 HCV) were treated with conventional postoperative immunosuppression. The overall incidence of rejection was similar with the two strategies of immunosuppression. With follow-ups of 14 to 22 months, patient and primary graft survival in HCV cases are 97% and 90%, respectively, with alemtuzumab depletion plus minimal immunosuppression versus 71% and 70%, respectively, under conventional immunosuppression. In HCV recipients, current patient and graft survival in the alemtuzumab-pretreated group are 71% and 70% versus 65% and 54%, respectively, under conventional treatment. With both strategies of immunosuppression, the adverse effect of preexisting HCV on survival parameters and graft function already was significant at the 1-year milestone, but its extent was not evident until the second year. With or without HCV, 62% of the 64 surviving lymphoid-depleted patients are on spaced immunosuppression, and four patients receive no immunosuppression. Lymphoid depletion with alemtuzumab and minimalistic maintenance immunosuppression is a practical strategy of liver transplantation in HCV recipients but not HCV recipients.

Bacteremias in liver transplant recipients: shift toward gram-negative bacteria as predominant pathogens.

During the 1990s, gram-positive bacteria emerged as major pathogens after liver transplantation. We sought to determine whether the pathogens associated with bacteremias in liver transplant recipients have changed. Patients included 233 liver transplant recipients transplanted between 1989 and 2003. The proportion of all infections due to bacteremias increased significantly over time (P <.0001). Of other major infections, a trend toward a decrease in fungal infections (P =.089) and a significant decrease in cytomegalovirus (CMV) disease (P =.0004) were documented. Whereas the proportion of bacteremias due to gram-negatives increased from 25% in the period of 1989-1993 to 51.8% in 1998-03, that of gram-positive bacteria decreased from 75% in the period of 1989-93 to 48.2% in the period of 1998-2003. Methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent pathogens in bacteremic patients. The incidence of bacteremias due to MRSA and Pseudomonas aeruginosa has remained unchanged (P <.20); however, that due to enteric gram-negative bacteria, particularly Klebsiella pneumoniae has increased (P =.02). Klebsiella pneumoniae isolates in the current quartile were not clonally related. In conclusion, bacteremias as a proportion of all infections in liver transplant recipients have increased significantly over time, due in part to a decline in infections due to other major pathogens, e.g., fungi, primarily Candida species, and CMV. Gram-negative bacteria have emerged as predominant pathogens in bacteremic liver transplant recipients.

Cryptococcus neoformans Infection in Patients With Cirrhosis, Including Liver Transplant Candidates.

We reviewed the cases of patients with cirrhosis, including liver transplant candidates, at our institution in the last 3 years (n = 5) and those individually described in the literature (n = 28), to assess unique characteristics and outcome of cryptococcosis in these patients. Sixty-four percent (21/33) of the patients had no other recognized immunosuppression. Peritonitis (in 45%, 15/33 of the patients) with modest pleocytosis in the ascitic fluid, was the most common presenting feature. Median time to detection of Cryptococcus in the ascitic fluid cultures was 6 days. Overall mortality rate was 81% (26/32); death was deemed attributable to cryptococcosis in 24/26 patients who died. Evaluation of culture-negative neutrocytic ascites in febrile cirrhotic patients warrants consideration of cryptococcal peritonitis.

Impact of evolving trends in recipient and donor characteristics on cytomegalovirus infection in liver transplant recipients.

BACKGROUND: This study determines whether the recipient and donor characteristics that influence the cytomegalovirus (CMV) infection rate after liver transplantation have changed. METHODS: The recipient and donor characteristics that may affect the rate of CMV infection were assessed in 232 liver transplant recipients at our institution during a 14-year period (1989-2003). RESULTS: Since 1989, the age of recipients (P=0.0001) and donors (P=0.0001) has increased significantly. Pretransplant CMV seropositivity in recipients has decreased significantly (P=0.0001, 86.4% [1989-1992] to 53.7% [2000-2003]), whereas donor CMV seropositivity has remained unchanged (P>0.20). As a result, there has been a significant increase in the proportion of high-risk (CMV recipient-/donor+) patients (P=0.012); 10.6% of recipients from 1989 to 1992 versus 24.1% of recipients from 2000 to 2003 were CMV recipient-/donor+. The Child-Pugh scores of recipients have remained unchanged over time. However, the proportion of patients undergoing transplantation while being cared for in the intensive care unit has decreased significantly over time (P=0.0002). Despite an increase in the rate of CMV infection (P=0.09), the incidence of CMV disease has decreased significantly (P=0.0004). CONCLUSIONS: The proportion of high-risk patients (CMV recipient-/donor+) has increased significantly over time, attributable largely to a declining rate of CMV seropositivity in recipients before transplantation. These data have implications for guiding prophylactic practices and resource use after liver transplantation.

Lack of efficacy of mupirocin in the prevention of infections with Staphylococcus aureus in liver transplant recipients and candidates.

BACKGROUND: Infections with Staphylococcus aureus are a significant problem in patients in liver transplant units. An association between prior nasal carriage with and subsequent infections has been documented previously in liver transplant recipients and patients with cirrhosis. However, the role of decolonization with mupirocin applied intranasally for the prevention of S. aureus infections in these patients has not been determined. METHODS: S. aureus nasal carriage was prospectively sought in 70 consecutive liver transplant candidates. Mupirocin two times per day for 5 days was administered to the carriers. Follow-up nasal cultures to document decolonization were performed 5 days after the final application of mupirocin. The primary endpoint was the development of S. aureus infections. RESULTS: Thirty-one of 70 patients (44%) were found to be nasal carriers and 27 of 31 nasal carriers (87%) were successfully decolonized. However, 12 of 27 patients (37%) successfully decolonized became recolonized with S. aureus, and an additional nine patients who were initially noncarriers became newly colonized with S. aureus during the study period. Despite the use of mupirocin, 16 of 70 patients (23%) developed an infection with S. aureus. No isolate was found to be mupirocin resistant. CONCLUSION: Elimination of S. aureus nasal carriage by mupirocin did not prevent S. aureus infections in patients in our liver transplant unit.

Safety and efficacy of isoniazid chemoprophylaxis administered during liver transplant candidacy for the prevention of posttransplant tuberculosis.

BACKGROUND: Optimal timing of initiation of isoniazid chemoprophylaxis in liver transplant recipients who test positive on the tuberculin skin test has not been defined. We sought to determine whether isoniazid prophylaxis administered during liver transplant candidacy was safe and effective for the prevention of posttransplantation tuberculosis. METHODS: During a 9-year period, 18 liver transplant candidates with tuberculin skin test greater than 5 mm or recent conversion to positive tuberculin skin test were identified and received isoniazid chemoprophylaxis for 12 months. For each case, a control matched with the patient for underlying liver disease and age (within 5 years of the case) was included. Liver function tests were assessed monthly. The median follow-up was 55 months and ranged up to 107 months for the cases. RESULTS: At baseline, the cases had a total bilirubin of 2.2 mg/dL, alanine aminotransferase of 106 IU/L, prothrombin time of 14.2 sec, and serum albumin of 2.9 gm/dL (mean values). Hepatic function tests did not differ significantly for the cases at 3, 6, 9, and 12 months when compared with those at baseline or between the cases and controls at each of the above time points. Discontinuation of prophylaxis was not required in any of the patients. The outcome (proportion of patients who underwent transplantation or were dead or alive at the last follow-up) and survival time for the cases did not differ significantly from those of the controls (P >0.20). CONCLUSION: In liver transplant candidates at risk for infection after transplantation, isoniazid chemoprophylaxis used during candidacy was well tolerated and did not adversely effect hepatic function or outcome as compared with the control patients.

Voriconazole inhibition of the metabolism of tacrolimus in a liver transplant recipient and in human liver microsomes.

The purpose of this study was to assess the effect of voriconazole on the blood tacrolimus concentration in a liver transplant recipient and to examine the interaction between voriconazole and tacrolimus by using human liver microsomes. Two subjects were enrolled in the clinical study: one received voriconazole, and the other received a placebo. Tacrolimus metabolism was evaluated in human liver microsomes at various concentrations in the absence and presence of various concentrations of voriconazole. Coadministration of voriconazole and tacrolimus resulted in elevated (nearly 10-fold-higher) trough tacrolimus blood concentrations in the liver transplant patient. In the in vitro study, voriconazole at a concentration of 10.4 +/- 4.3 micro g/ml inhibited the metabolism of tacrolimus by 50%. Clinically relevant concentrations of voriconazole inhibited the metabolism of tacrolimus in human liver microsomes. Close monitoring of the blood concentration and adjustment in the dose of tacrolimus are warranted in transplant recipients treated with voriconazole.

Bleeding complications precipitated by unrecognized Gingko biloba use after liver transplantation.

Because of its neurocognitive enhancing effects, Gingko biloba has emerged as amongst the most commonly used herbal products. We report a liver transplant recipient with potentially life-threatening toxicity resulting from Gingko biloba use. Seven days after a second liver transplantation for recurrent hepatitisB virus infection, subphrenic hematoma was documented in a 59-year-old Korean patient. Failure to control bleeding with CT-guided drainage necessitated exploratory laparotomy for the evacuation of a large subphrenic hematoma. Three weeks later, an episode of vitreous hemorrhage was documented. Unbeknownst to his care providers, the patient had been consuming Gingko biloba throughout the postoperative period. No further bleeding episodes occurred after the cessation of Gingko biloba use. Unrecognized use of herbal products may be associated with serious side effects and adverse clinical sequelae in transplant recipients. Given their increasing popularity, the use of herbal products should be routinely sought as part of the history in transplant recipients.

Pharmacokinetics of cefoperazone and sulbactam in liver transplant patients.

The authors evaluated the pharmacokinetics of cefoperazone and sulbactam in 9 liver transplant patients. Cefoperazone and sulbactam were administered as an intravenous infusion over 30 minutes every 12 hours for six doses, and multiple blood samples were collected immediately after the first dose (administered during the surgery) and after the last dose. The concentrations of cefoperazone and sulbactam in serum and, when possible, in urine and bile collected over one dosing interval were measured by high-pressure liquid chromatography. The concentration of cefaperazone ranged from 436 to 4118 microg/ml, and sulbactam ranged from 3.3 to 8.7 microg/ml in the bile samples. The intraoperative clearance of cefoperazone (0.53+/-0.18 ml/min/kg) was significantly higher than the postoperative clearance (0.21+/-0.23 ml/min/kg). The half-life of cefaperazone, although not statistically significantly different, was prolonged in all patients during the postoperative period. The clearance of sulbactam (1.51+/-0.51 ml/min/kg) was lower than what is reported in patients with normal renal function but was comparable to what has been reported in patients with renal impairment and in critically ill patients. There were no significant differences in any of the pharmacokinetic parameters of sulbactam during and after surgery. The pharmacokinetic parameters of cefoperazone and sulbactam were significantly altered in liver transplant patients compared to what has been reported in normal subjects but were similar to what has been reported in patients with liver and renal impairment. There was a significant impairment in the biliary excretion of cefoperazone during the postoperative period in liver transplant patients. Although the percentage of the dose of cefoperazone excreted in the bile was drastically reduced, the biliary concentrations were generally high and above the MIC for most organisms. Given that both renal and hepatic elimination of cefoperazone is decreased, leading to a lower clearance and longer half-life in liver transplant patients, lower doses (1-2 g per day) of cefoperazone may be sufficient in liver transplant patients during the immediate postoperative period.

Impact of human herpesvirus-6 on the frequency and severity of recurrent hepatitis C virus hepatitis in liver transplant recipients.

A role of tumor necrosis factor-alpha (TNF-alpha) In the immunopathogenesis of hepatitis C virus (HCV) infection has been proposed. The novel herpes virus, human herpes virus-6 (HHV-6), is amongst the most potent inducers of cytokines, including TNF-alpha. The impact of HHV-6 viremia on the progression of recurrent HCV hepatitis was assessed in 51 HCV-positive liver transplant recipients. The frequency of recurrent HCV hepatitis did not differ between patients with HCV viremia (47.6%, 10/21) as compared with those without HCV viremia (46.7%, 14/30, p = 0.9). However, the patients with HHV-6 viremia had a significantly higher fibrosis score upon HCV recurrence than those without HHV-6 viremia (mean 1.5 vs. 0.3, p = 0.01). An association between cytomegalovirus (CMV) viremia and HCV recurrence was not documented; 50% (15/30) of the patients with CMV viremia and 42.8% (9/21) of those without CMV viremia had recurrent HCV hepatitis (p > 0.5). Receipt of ganciclovir (administered upon the detection of CMV viremia) was associated with lower total Knodell score (mean 5.2 vs. 6.9, p = 0.05) and a trend towards lower fibrosis score (mean 0.44 vs. 1.00, p = 0.12) in patients with recurrent HCV hepatitis. Thus, HHV-6 viremia in HCV-positive liver transplant recipients identified a subgroup of patients at increased risk for early fibrosis upon HCV recurrence.

Trends in invasive fungal infections in liver transplant recipients: correlation with evolution in transplantation practices.

BACKGROUND: The incidence of invasive fungal infections, particularly invasive candidiasis, after liver transplantation is strongly influenced by surgical factors and technical complexity of the surgery. We assessed the temporal trends in invasive fungal infections in the context of evolution in liver transplantation practices, technical developments, and other risk factors. METHODS: Demographic and clinical characteristics of the patients, transplantation-related variables, and rates of infection were longitudinally analyzed over the last 10 years in 190 consecutive liver transplant recipients at our institution. Trends for categorical data were evaluated using the Cochran-Armitage trend test and for continuous variables using analysis of variance with linear contrast. RESULTS: A decrease in the length of operation (P=0.03), intraoperative transfusion requirements (P=0.0001), cold ischemic time (P<0.0001), use of roux-en-Y biliary anastomosis (P=0.0015), rate of biopsy proven rejection (P<0.0001), and retransplantation (P=0.056) was documented over the successive years. A significant decline in Child-Pugh score (P=0.02) and in the proportion of patients transplanted as UNOS 2a occurred (P=0.0001). Although the incidence of cytomegalovirus infection remained unchanged, a significant increase in the frequency of primary cytomegalovirus infection (P=0.045), and a decrease in cytomegalovirus disease (P=0.0006) was documented. Over the same time period, a significant decrease in the incidence of invasive candidiasis (P=0.015), and an insignificant increase in the rate of invasive aspergillosis (P=0.20) occurred. CONCLUSION: Notable technical developments in liver transplantation practices and risk profiles of patients have occurred over the decade. These variables may have a role in influencing the evolving trends in invasive fungal infections in liver transplant recipients.