Unique characteristics of cryptococcosis identified after death in patients with liver cirrhosis: comparison with concurrent cohort diagnosed antemortem.

Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.

Micafungin versus amphotericin B lipid complex for the prevention of invasive fungal infections in high-risk liver transplant recipients.

BACKGROUND: Limited data exist regarding echinocandins as antifungal prophylaxis in liver transplant recipients. METHODS: The efficacy and safety of targeted prophylaxis with micafungin or amphotericin B lipid complex (ABLC) was assessed in a sequential cohort of high-risk patients (posttransplantation dialysis, retransplantation, or reoperation) and compared with those without high risk who did not receive prophylaxis. Outcomes were assessed at 90 days. RESULTS: Micafungin versus ABLC recipients were older (P=0.0065) and more likely to have hepatocellular carcinoma (P=0.025). High-risks, that is, dialysis (55.6% vs. 79.2%), retransplantation (5.6% vs. 12.5%), and reoperation (38.9% vs. 20.8%) did not differ between the two groups. Invasive fungal infections developed in 11.1% (2 of 18) of micafungin recipients, 8.3% (2 of 24) of ABLC recipients, and 3% (7 of 234) of patients without high risks (P=0.12). In nondialyzed patients, ABLC versus micafungin recipients had significantly higher serum creatinine on day 14 (P=0.04). However, renal and hepatic function, rejection, graft loss, and mortality did not differ for the two groups on day 90. CONCLUSIONS: Targeted prophylaxis with micafungin or ABLC decreased the risk of mycoses in high-risk recipients compared with that in low-risk recipients. Compared with ABLC, however, micafungin appeared to be associated with lower early-renal dysfunction and no additional risk of hepatic dysfunction.

Impact of rifaximin use for hepatic encephalopathy on the risk of early post-transplant infections in liver transplant recipients.

BACKGROUND: Whether the use of rifaximin for hepatic encephalopathy during liver transplant candidacy has an impact on post-transplant infections is not known. METHODS: We compared the frequency and spectrum of infections within 90 d post-transplant in liver transplant recipients who did and did not receive rifaximin for hepatic encephalopathy during transplant candidacy. RESULTS: Of 110 consecutive liver transplant recipients, 30 (27%) received rifaximin. Rifaximin users were more severely ill based on higher Model for End-Stage Liver Disease (MELD) score (p=0.005). When controlled for MELD (stratified by MELD<30, MELD≥30), the risk of infections was significantly lower in rifaximin vs. no rifaximin recipients (OR=0.269, 95% CI 0.078-0.0.934, p=0.026). Rifaximin use was not associated with a higher risk of multidrug resistant bacterial infections (OR=1.8, 95% CI 0.42-8.35, p=0.40). The probability of post-transplant survival at 90 d did not differ for patients with or without rifaximin use (0.90 for both groups, p=0.56). CONCLUSIONS: Rifaximin appeared to have a protective effect against early post-transplant infections in more severely ill liver transplant recipients. Rifaximin use did not select for multidrug resistant bacteria in these patients.

Impact of the duration of posttransplant renal replacement therapy on bacterial infections in liver transplant recipients.

Whether the duration of renal replacement therapy (RRT) after liver transplantation influences the rate and types of bacterial infections is not known. In this study, 47 of 299 consecutive liver transplant recipients (16%) required posttransplant RRT. The incidence of bacterial infections was higher in the RRT group versus the non-RRT group (8.84 versus 1.38 per 1000 patient days, P < 0.001). In the RRT group, 49% of the patients (23/47) required long-term RRT (≥30 days), and 51% (24/47) required short-term RRT (<30 days). Long-term RRT (hazard ratio = 2.27, 95% confidence interval = 1.16-4.47, P = 0.017) was a significant predictor of infections. Bacteremia and intra-abdominal infections were the most common sources of infections, and Enterobacteriaceae and enterococci were the predominant pathogens in both groups. The mortality rate for patients requiring RRT was higher than the rate for patients not requiring RRT (P < 0.001), but the mortality rates of the short-term RRT group and the long-term RRT group did not significantly differ (P = 0.654). In conclusion, although both short-term RRT and long-term RRT confer a higher risk of bacterial infections, only long-term RRT is a statistically significant predictor of these infections.

Identifying a targeted population at high risk for infections after liver transplantation in the MELD era.

Impact of model for end-stage liver disease (MELD) scoring system on post-transplant infections and associated risk factors are unknown. Infections <90 d post-transplant were assessed in 277 consecutive liver transplant recipients from 1999 to 2008. "High-risk" factors for infections were pre-defined as MELD score >30, ICU stay >48 h prior to transplant, intraoperative transfusion ≥15 units, retransplantation, post-transplant dialysis, or reoperation. Of the 240 recipients in the MELD era (2002-2008), 48.5% had any high-risk factor. The OR for infection was 1.69, 2.00, 18.00, and 4.50 in recipients with any 1, 2, 3, and ≥4 high-risk factors, respectively (χ(2) for trend, p < 0.001). In logistic regression model, recipient age (OR 1.12, p < 0.05) and any high-risk factor (OR 2.42, p < 0.05) were associated with infections. Compared with 37 pre-MELD recipients, the overall infections and mortality at 12 months did not differ in the two eras. In Cox regression model, recipient age (OR 1.09, p < 0.05) and any high-risk factor (OR 2.42, p < 0.05) remained associated with infections. The overall frequency of infections did not increase in the MELD era. Pre-defined risk factors accurately predicted the risk of infections in these patients.

Preemptive therapy for cytomegalovirus based on real-time measurement of viral load in liver transplant recipients.

BACKGROUND: Real-time PCR has emerged as the preferred diagnostic assay for CMV. However, its utility as a preemptive therapy tool for CMV disease and related outcomes in liver transplant recipients has not been fully defined. METHODS: Patients comprised 117 consecutive liver transplant recipients who underwent CMV surveillance monitoring using real-time PCR. Preemptive therapy with valganciclovir was employed upon detection of viremia. Baseline viral load was considered high based on log values (median). RESULTS: CMV viremia developed in 54% (63/117) of the patients, including 77% of R-/D+, 63% of R+/D+, 43% of R+/D-, and 10% of R-/D- patients. Overall, 23% (15/63) of the patients had recurrent viremia; R- serostatus (p=0.065) but not initial viral load correlated with recurrent viremia (p=0.80). At 12 months post-transplant, CMV disease occurred in 0.85% (1/117) of the patients (R+/D+recipient). None (0/30) of the R-/D+patients had CMV disease. Patients with CMV viremia treated preemptively did not differ significantly from those who never developed CMV viremia with regards to bacterial or fungal infections, rejection, graft loss, mortality rate, and probability of survival at 12 months (p>0.05 for all variables). The above outcomes also did not differ for patients with high (>1.9 logs) vs. low viral load (<1.9 logs) (p>0.05 for all outcomes). CONCLUSIONS: Preemptive therapy guided by real-time PCR based monitoring led to outcomes in all patients or in those with high viral loads that were comparable to outcomes in patients who never developed viremia or had low viral loads, respectively. Late-onset CMV disease at 12 months was observed in <1% of all patients.

Pretransplant cryptococcosis and outcome after liver transplantation.

The posttransplant outcomes and optimal management of patients with end-stage liver disease who develop cryptococcosis prior to transplantation have not been defined. We discuss these issues in the context of successful liver transplantation and pretransplant cryptococcal disease. Our report suggests that liver transplantation may be cautiously considered under the umbrella of fluconazole therapy in patients with end-stage liver disease and pretransplant cryptococcosis, provided that disease control is achieved with adequate treatment before transplantation.

Impact of pretransplant infections on clinical outcomes of liver transplant recipients.

Whether pretransplant nonviral infections influence outcomes after transplantation in liver transplant recipients in the current era is not well defined. One hundred consecutive patients undergoing liver transplantation in 2005-2008 were studied. Demographics, posttransplant clinical events, and mortality were compared between recipients with and without infections within 12 months before transplantation. In all, 32% of the patients (32/100) developed 45 episodes of pretransplant infections, which included spontaneous bacterial peritonitis (35.6%), bloodstream infections (28.9%), cellulitis (13.3%), pneumonia (8.9%), urinary tract infections (6.7%), and other infections (6.7%). Compared with 68 recipients without pretransplant infections, those with infections had a higher Model for End-Stage Liver Disease score and a lower likelihood of transplantation from home and required longer and more frequent hospital care before and after transplantation (P < 0.05). Mortality at 90 (9.4% versus 2.9%) and 180 days (15.6% versus 10.3%) post-transplant did not differ significantly between recipients with and without pretransplant infections (P = not significant). A higher Model for End-Stage Liver Disease score (P < 0.05) and posttransplant infections (P < 0.05 and P < 0.001), but not pretransplant infections, were associated with posttransplant mortality at 90 and 180 days. In conclusion, pretransplant infections that have been adequately treated do not pose a significant risk for poor outcomes, including posttransplant mortality.

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-1beta, IL-12p70, and IFN-gamma), 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.

Protothecosis after liver transplantation.

Prototheca species are unicellular algae of low virulence that are rarely associated with human infections. We report a liver transplant recipient with disseminated protothecosis and review the literature on this unusual opportunistic infection in transplant recipients. Of 9 cases, including ours, 5 had a localized infection, and 4 had disseminated protothecosis. Seven cases were due to Prototheca wickerhamii, and 2 were due to Prototheca zopfii. Overall mortality in transplant recipients with Prototheca infections was 88% (7/8). All 4 cases of disseminated protothecosis died despite therapy with amphotericin B. Posttransplant protothecosis is a rare but significant infection that is associated with a grave prognosis.

Valganciclovir as preemptive therapy for cytomegalovirus in cytomegalovirus-seronegative liver transplant recipients of cytomegalovirus-seropositive donor allografts.

The efficacy of valganciclovir as preemptive therapy for the prevention of cytomegalovirus (CMV) disease and its impact on indirect sequelae of CMV were assessed in recipient-negative/donor-positive (R-/D+) liver transplant recipients. Of 187 consecutive liver transplant recipients at our institution since July 2001, 36 (19.2%) belonged to the R-/D+ group. Surveillance tests for CMV were performed on all patients at weeks 2, 4, 6, 8, 10,12, and 16. In all, 27 patients with asymptomatic viremia received preemptive therapy with valganciclovir. At a total follow-up of 62.8 patient years (median: 19 months, range: 3 months to 5.6 years), no episodes of CMV disease were documented in these patients. The incidence of rejection, retransplantation, and bacterial or fungal infections and the probability of survival did not differ for R-/D+ patients and all non-R-/D+ patients treated preemptively with valganciclovir (P > 0.20 for all variables). Thus, preemptive therapy with valganciclovir in R-/D+ patients was not associated with CMV disease during the period of surveillance monitoring or at anytime thereafter (late-onset CMV disease). The indirect outcomes with the use of valganciclovir in R-/D+ patients were comparable to the outcomes of other subgroups of liver transplant recipients receiving preemptive therapy.

Impact of the MELD score on waiting time and disease severity in liver transplantation in United States veterans.

Organ allocation for liver transplantation (LT) in the United States is based on the Model for End-Stage Liver Disease (MELD) score. The MELD score prioritizes organ distribution to sicker patients. There is limited data on the effect of this policy on transplantation in the Veterans Affairs (VA) healthcare system. The aim of this study was to determine the impact of the MELD score on U.S. veteran patients undergoing LT. Comparison of MELD scores and waiting time of LT recipients before and after the introduction of the MELD system was done. A total of 192 LT recipients were analyzed. Blood type, diagnosis, listing MELD score, and Child-Turcotte-Pugh (CTP) score at transplant did not differ although MELD era recipients were older (mean 54.3 vs. 51.3 yr, P = 0.009). Mean waiting time decreased from 461 days (pre-MELD) to 252 days (MELD era) (P = 0.004). Mean MELD score at LT increased from 23.4 (MELD era) compared to 20.3 (pre-MELD) (P = 0.01). In conclusion, waiting time for LT in U.S. veterans has decreased significantly in the MELD era. The MELD score of patients transplanted in the MELD era is significantly higher and patients are still being listed at a high MELD score. The MELD system has lead to sicker veterans being transplanted with shorter waiting times.

Hepatic iron content and the risk of Staphylococcus aureus bacteremia in liver transplant recipients.

Iron is a critical nutrient source and contributes to staphylococcal pathogenesis. We assessed the role of hepatic explant iron overload as a risk factor for Staphylococcus aureus bacteremia in liver transplant recipients. Seven of 13 cases with S aureus bacteremia (53.8%) had hepatic explant iron concentrations that exceeded normal limits (grade > or = 2). Length of posttransplant intensive care unit stay (P= .013) and hepatocellular carcinoma as underlying liver disease (P = .04), but not hepatic explant iron concentration, correlated with a higher risk of S aureus bacteremia after transplantation. However, noncarriers (patients without S aureus nasal carriage) who developed S aureus bacteremia were more likely to have high hepatic iron content; 4 of 7 (57%) noncarriers with high-grade iron content developed S aureus bacteremia but no noncarriers with low-grade iron content did (P = .07). All noncarriers who became infected had high iron content (grade > or = 2) of the hepatic explant. A readily quantifiable assessment of hepatic iron at the time of transplantation can potentially identify patients without carriage who may be at risk for early S aureus bacteremia.

Alternative therapy use in liver transplant recipients.

BACKGROUND: The extent of use of alternative therapies and the psychosocial variables predictive of their use have not been well defined in liver transplant recipients. OBJECTIVE: To determine types of alternative therapies used by liver transplant recipients and to assess psychosocial, behavioral, and quality of life variables associated with the use of alternative therapies in these patients. METHODS: Assessment of types of alternative therapies used, demographic characteristics, satisfaction with social support, coping styles, sense of personal control (mastery), quality of life, and health beliefs in 32 liver transplant recipients. RESULTS: Overall, 34.4% of the liver transplant recipients used a form of alternative therapy. Herbal products were used by 45% of the alternative therapy users and included milk thistle (silymarin), eclipta, and green beet leaf-all considered "hepatic tonics". Alternative therapy users tended to have greater problem-focused coping skills than nonusers (P = .08). Nineteen percent of the patients incurred annual out-of-pocket expense of at least dollars 100 for alternative therapies. Patients incurring out-of-pocket expenses reported better overall health (P = .02), were more likely to be employed (P = .025), and had higher mastery scores (P = .01). CONCLUSIONS: Use of alternative therapies is common after liver transplantation. Herbal products used by liver transplant recipients are disease specific; that is, they claim to promote liver health.

Invasive aspergillosis in the recipients of liver retransplantation.

Retransplantation is a major risk factor for invasive aspergillosis in liver transplant recipients. However, the risk for invasive aspergillosis with time elapsed since retransplantation, clinical characteristics, and outcome of patients who develop this infection after retransplantation of the liver has not been defined. Patients comprised 17 liver retransplant recipients with invasive aspergillosis between 1990 and 2004. Retransplantation was considered early if it was performed within 30 days and late if performed after 30 days of the first or primary transplant. Retransplant recipients comprised 25% of all cases of invasive aspergillosis after liver transplantation. Fifty-three percent of the Aspergillus infections occurred within 30 days, and 76% within 90 days of retransplantation. In all, 53% (9/17) of the patients were late retransplant recipients. Late compared to early retransplant recipients with invasive aspergillosis were more likely to have central nervous system involvement with invasive aspergillosis (56% vs. 0%, P = 0.03). Mortality rate was 100% for late and 63% for early retransplant recipients with Aspergillus infections. In conclusion, time-varying risk for invasive aspergillosis after retransplantation has implications relevant for guiding antifungal prophylaxis. Given a greater risk for disseminated infection and poor outcome in late retransplant recipients with aspergillosis, potent and aggressive antifungal therapy should be considered upfront in these patients.

Impact of an aggressive infection control strategy on endemic Staphylococcus aureus infection in liver transplant recipients.

BACKGROUND: Methicillin-resistant Staphylococcus aureus has emerged as a leading pathogen in transplant recipients and has become endemic in many institutions where transplantation is performed. The role of active surveillance programs based on the detection of colonization in the prevention of S. aureus infection in liver transplant recipients has not been defined. METHODS: A total of 47 consecutive patients who underwent liver transplantation during 1996-1999 were compared with 97 patients who received a liver transplant during 2000-2004 after implementation of an intensive intervention program that included use of surveillance cultures to detect nasal and rectal colonization, use of cohorting and contact isolation precautions, and decolonization with intranasal mupirocin therapy. RESULTS: The rate of new acquisition of S. aureus colonization of nares after transplantation decreased from 45.6% (21 of 46 patients) during the preintervention period to 9.9% (9 of 91 patients) during the postintervention period (P<.001). An increased length of hospital stay (odds ratio, 1.03; 95% confidence interval, 1.01-1.05; P<.002) was associated with new carriage acquisition, and transplantation during the postintervention period (odds ratio, 0.21; 95% confidence interval, 0.08-0.51; P<.001) was independently protective against new carriage. The rate of infection due to S. aureus decreased from 40.4% (19 of 47 patients) during the preintervention period to 4.1% (4 of 97 patients) during the postintervention period (P<.001), and the rate of bacteremia decreased from 25.5% (12 of 47 patients) to 4.1% (4 of 97 patients), respectively (P<.001). Overall, S. aureus infections occurred more frequently among patients with new carriage than among patients who were carriers at the time of transplantation (P<.001) or patients who were noncarriers (P<.001). CONCLUSIONS: Use of active surveillance cultures to detect colonization and implementation of targeted infection control interventions proved to be effective in curtailing new acquisition of S. aureus colonization and in decreasing the rate of S. aureus infection that was endemic in our population of liver transplant recipients.

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.

Who among cytomegalovirus-seropositive liver transplant recipients is at risk for cytomegalovirus infection?

A vast majority of the transplant recipients are cytomegalovirus (CMV)-seropositive (R+). We sought to assess variables predictive of CMV infection, specifically in R+ liver transplant recipients. Study patients comprised 182 consecutive liver transplant recipients who survived at least 14 days after transplantation. Surveillance testing was used to detect CMV infection. Pre-emptive therapy was employed for the prevention of CMV disease, however, no antiviral prophylaxis was used for CMV infection. CMV infection developed in 32.5% (38 of 117) of R+ patients, 84.6% (33 of 39) of R-/D+, and 3.8% (1 of 26) of R-/D- patients. In R+ patients, Hispanic race (21.6% vs. 7.8%, P = 0.06), donor CMV seropositivity (73.7% vs. 45.6%, P = 0.005), and hepatocellular carcinoma (23.7% vs. 6.3%, P = 0.05) correlated with a higher risk of CMV infection. In a multivariate model, Hispanic race (OR: 3.5, 95% CI: 1.03-11.6, P = 0.045), donor CMV serostatus (OR: 4.0, 95% CI: 1.6-10.2, P = 0.003) and hepatocellular carcinoma (OR: 5.8, 95% CI: 1.6-20.5, P = 0.006) were all significant independent predictors of CMV infection. The aforementioned variables did not portend a higher risk of CMV infection in R-/D+ patients; donor CMV seropositivity overwhelmed all other risk factors in R- patients (P < 0.00001). In conclusion, CMV-seropositive liver transplant recipients at risk for CMV infection can be identified based on readily assessable variables. Preventive strategies may be selectively targeted toward these patients.

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.