Cytomegalovirus infection in liver transplant recipients: Updates on clinical management

Cytomegalovirus (CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years, and clinical guidelines have been recently updated. Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. A currently-recruiting randomized clinical trial is comparing the efficacy and safety of the two prevention strategies in the highest risk D+R- liver recipients. Drug-resistant CMV infection remains uncommon but is now increasing in incidence. This highlights the currently limited therapeutic options, and the need for novel drug discoveries. Immunotherapy and antiviral drugs with novel mechanisms of action are being investigated, including letermovir (AIC246) and brincidofovir (CMX001). This article reviews the current state of CMV management after liver transplantation, including the updated practice guidelines, and summarizes the data on investigational drugs and vaccines in clinical development.     

Management of cytomegalovirus infection and disease in liver transplant recipients

Cytomegalovirus(CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferredstrategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/Rliver transplant recipients, and such occurrence of lateonset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach(antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effective as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ(including liver) transplant recipients. The aim of this article is to provide a state-of-the art review of the epidemiology, diagnosis, prevention, and treatment of CMV infection and disease after liver transplantation.     

Current concepts on cytomegalovirus infection after liver transplantation

Cytomegalovirus (CMV) is the most common viral pathogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted allograft. In addition, CMV has been significantly associated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, one should also reduce the degree of immunosuppression. In one recent controlled clinical trial, valganciclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. In this article, the authors review the current state and the future perspectives of prevention and treatment of CMV disease after liver transplantation.     

Update on Cytomegalovirus Infections of the Gastrointestinal System in Solid Organ Transplant Recipients

Cytomegalovirus (CMV) infection of the gastrointestinal tract is the most common manifestation of tissue-invasive CMV disease, and is a significant cause of morbidity and mortality in the solid organ transplantation (SOT) recipient. In addition to the direct effects of the infection, its indirect effects on allograft function, risk for other opportunistic infections, and mortality are significant in this population. The most common clinical syndromes are esophagitis, colitis, and hepatitis; however, infection can occur anywhere in the gastrointestinal tract. Diagnosis is usually by histopathology or viral culture of tissue specimens; molecular assays also often have a role. Antivirals are the cornerstone of therapy for gastrointestinal tract CMV disease and complications such as recurrent infection and antiviral resistance are not uncommon. Prevention with antiviral prophylaxis or preemptive therapy is important. This review summarizes recent data regarding the clinical manifestations, diagnosis, treatment, and prevention of gastrointestinal tract CMV infection in the SOT population.     

Cytomegalovirus infection after liver transplantation： Current concepts and challenges

Cytomegalovirus （CMV） is a common viral pathogen that influences the outcome of liver transplantation. In addition to the direct effects of CMV syndrome and tissue-invasive diseases, CMV is associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. Risk factors for CMV disease are often interrelated, and include CMV D＋/R- serostatus, acute rejection, female gender, age, use of high-dose mycophenolate mofetil and prednisone, and the overall state of immunity. In addition to the role of CMV-specific CD4＋ and CD8＋ T lymphocytes, there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis. In one study, liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher levels of CMV replication and clinical disease. Because of the direct and indirect adverse effects of CMV disease, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component in improving the outcome of liver transplantation. In the majority of transplant centers, antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors （D＋/R-）. However, the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease. In several prospective and retrospective studies, the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D＋/R- liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention and novel drugs with unique modes of action are needed. Currently, a randomized controlled clinical trial is being perf     

High-dose acyclovir and pre-emptive ganciclovir in prevention of cytomegalovirus disease in pediatric patients following peripheral blood stem cell transplantation

Cytomegalovirus (CMV) disease remains an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). We evaluated high-dose acyclovir (HDACV) and pre-emptive ganciclovir to prevent CMV disease in 76 children who underwent peripheral blood stem cell transplantation (PBSCT) and were at risk for CMV reactivation and disease (both recipient and donor seropositive) from May 1998 to April 2003. All received HDACV from day -9 to 6 months post transplant in conjunction with weekly CMV pp65 antigenemia monitoring. The incidence of antigenemia in this cohort was 19.7%, at a median of 22 days post-PBSCT. The frequencies were 26.4 and 4.4% in allogeneic and autologous groups, respectively (P=0.03). Patients with nonmalignant disease had higher CMV antigenemia than those with malignant disease (30.8 vs 8.1%, P=0.02). Age at PBSCT, sex, graft-versus-host disease (GVHD) prophylaxis regimen and presence of acute GVHD did not affect the risk of CMV antigenemia. None of the patients who had positive pp65 antigenemia developed CMV disease during the study period. We conclude that pp65 antigenemia-guided HDACV and pre-emptive ganciclovir may prevent CMV disease in children undergoing PBSCT.     

Cytomegalovirus viral load monitoring after allogeneic bone marrow transplantation in patients receiving antiviral prophylaxis

Cytomegalovirus viral load measurement is a powerful new tool for monitoring of CMV disease; however, the optimal strategy for use is unknown. Weekly plasma CMV viral loads and CMV-related outcomes were monitored in 46 consecutive allogeneic bone marrow transplantation (BMT) recipients receiving standardised antiviral prophylaxis. A total of 412 CMV viral loads were quantitated in the first 100 days post transplantation with 77 positive samples (19%) in 20 patients (43%). No patient with all negative CMV viral load results developed CMV disease. Two of three patients with highly positive CMV viral loads (first positive < or =30 days post transplant, maximum viral load > or =5000 copies/ml, and > or =50% of samples positive) developed CMV disease. A total of 17 patients with positive CMV viral loads, who did not meet the criteria for highly positive, did not develop CMV disease. CMV viral load detection was higher in recipients who were CMV sero-positive. In conclusion, CMV disease did not occur in the setting of a persistently negative CMV viral load. A positive CMV viral load result occurred commonly after allogeneic BMT, even in patients receiving antiviral prophylaxis.     

Prevention of cytomegalovirus infection and disease after lung transplantation: results using a unique regimen employing delayed ganciclovir

BACKGROUND: Many lung transplant programs employ lengthy regimens of IV ganciclovir therapy to prevent disease due to cytomegalovirus (CMV). In 1994, we introduced a regimen of delayed ganciclovir prophylaxis for CMV infection. This consisted of 2 weeks of IV ganciclovir therapy, initiated 3 to 4 weeks after transplantation, with subsequent viral monitoring and preemptive therapy as needed. When not receiving ganciclovir, patients received oral acyclovir, 800 mg tid, for 6 months. CMV-seronegative patients with seropositive donors also received four doses of CMV hyperimmune globulin. This study analyzes the CMV outcomes of 54 patients who received the delayed regimen compared to 33 historical control subjects who received only acyclovir prophylaxis (n = 28) or oral acyclovir and 2 to 4 weeks of ganciclovir early after transplantation (n = 5). METHODS: CMV detection was by shell vial culture or IgG seroconversion; after 1996, CMV detection was by blood antigenemia. The diagnosis of CMV disease also required a typical clinical syndrome or pathologic evidence of CMV. The main outcome was the actuarial incidence of CMV infection and disease. In order to account for the effect of other important risk factors for CMV infection, the time to CMV infection and disease was also studied as dependeant variables in a Cox proportional-hazard analysis, with the delayed regimen and other important risk factors as independent variables. RESULTS: The delayed regimen reduced the actuarial incidence of CMV infection from 80 to 48% (p < 0.001) and CMV disease from 31 to 10% (p < 0.01). No seropositive patient receiving the delayed regimen developed CMV disease. Twelve of the 54 patients in the study group required additional IV antiviral treatment, but the total use of ganciclovir averaged only 18 days per patient. In a Cox proportional-hazards model, the use of delayed ganciclovir was the only factor that showed a significant association with freedom from CMV infection (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.24 to 0.75; p = 0.003) and CMV disease (HR, 0.29; 95% CI, 0.10 to 0.86; p = 0.03). CONCLUSION: A regimen of CMV prophylaxis employing 2 weeks of IV ganciclovir initiated 3 to 4 weeks after lung transplantation followed by virologic monitoring and preemptive therapy as needed provides good protection against CMV disease.     

The economic value of valacyclovir prophylaxis in transplantation

Cytomegalovirus (CMV) infection and disease, with its extensive direct and indirect consequences, adds considerably to the cost of patient management in both solid organ and bone marrow transplantation. Antiviral prophylaxis for CMV infection can offer cost advantages over preemptive therapy and "wait-and-treat" approaches. Valacyclovir has demonstrated efficacy for CMV prophylaxis in renal, heart, and bone marrow transplantation and is cost-effective when compared with placebo in renal transplant recipients at high risk of CMV infection. In reducing CMV infection and disease, valacyclovir prophylaxis appears to be associated with reductions in indirect effects of CMV (acute graft rejection, other opportunistic infections) and, if these effects are considered, the potential exists for even greater savings to be made with valacyclovir therapy. Benefits of valacyclovir in transplantation extend beyond CMV to other herpesviruses and may be increased in some clinical situations by prolonging prophylaxis beyond 3 months.     

Cidofovir as primary pre-emptive therapy for post-transplant cytomegalovirus infections.

Pre-emptive antiviral therapy for CMV infection following allogeneic stem cell transplantation is an effective strategy for preventing CMV disease. This entails the logistic difficulty of daily intravenous therapy with ganciclovir or foscarnet to clinically asymptomatic patients. Cidofovir (CDV) is effective against CMV in vitro and has the practical advantage of weekly administration. However, there are limited data on the pre-emptive use of CDV in CMV infections. We carried out a pilot study exploring the efficacy and toxicity of CDV as primary pre-emptive therapy for CMV infections monitored by PCR-based assays. CDV was used at 5 mg/kg with probenecid and hydration, weekly for a maximum of 4 weeks, followed by fortnightly maintenance treatment. Four patients were treated with CDV and two of them responded. Both the non-responders developed CMV disease. There was no renal toxicity noted in any of the patients, but three patients had severe vomiting and one developed uveitis, which precluded maintenance treatment in the two responders. Following failure of CDV, foscarnet was effective in controlling the CMV infection in both patients, although the infection recurred in both. Thus, larger randomised studies are required before CDV can be recommended as a primary pre-emptive therapy for post-transplant CMV infections.     

Management of cytomegalovirus infection in solid organ transplantation

Cytomegalovirus (CMV) infections are among the most common infections that occur following solid organ transplantation. CMV disease ranges from asymptomatic viremia, to CMV syndrome, to tissue-invasive disease. As CMV prophylaxis, treatment, diagnostics, and overall awareness have improved, the general trend has been towards earlier diagnosis of CMV disease and more mild clinical presentations in solid organ transplant recipients. Major stumbling blocks remain in the areas of duration of prophylaxis for the individual recipient, in the identification of which patients might need secondary prophylaxis, in the treatment of resistant virus, and in the possible use of the adoptive transfer of CMV-specific T cells. Several guidelines have been published during the past few years regarding the management of CMV in solid organ transplant recipients. This Review covers CMV diagnostics, methods for the prevention of CMV infection, treatment of both regular and drug-resistant CMV, as well as future directions for CMV management and research.     

Cytomegalovirus antigenemia and outcome of patients treated with pre-emptive ganciclovir: retrospective analysis of 241 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation

CMV disease remains a major infectious complication after allogeneic hematopoietic stem cell transplantation (HSCT). To investigate the relationship between CMV antigenemia, treatment with ganciclovir (GCV), and outcome, we retrospectively analyzed 241 consecutive patients at risk for CMV infection who underwent allogeneic HSCT. Antigenemia-guided pre-emptive strategy with GCV was used for all patients. CMV antigenemia developed in 169 patients (70.1%), and CMV disease in 18 patients (7.5%). Multivariate analysis showed that acute GVHD (grades II-IV) was the only risk factor for developing antigenemia, and acute GVHD and advanced age for CMV disease. GCV use, as well as acute GVHD and advanced age, significantly increased the risk for bacterial and fungal infection after engraftment. Those who developed CMV antigenemia had a poorer outcome than those who did not (log-rank, P=0.0269), although the development of CMV disease worsened the outcome with only borderline significance (log-rank, P=0.0526). In conclusion, detection of antigenemia proved to be a poor prognostic factor for HSCT patients, which may be attributed to a combination of factors, including CMV disease itself, the effect of treatment, and a host status that allows for reactivation of CMV. Optimal pre-emptive strategy needs to be determined.     

Cytomegalovirus infection and disease after liver transplantation

Cytomegalovirus is the single most important pathogen in clinical transplantation. Although much progress has been made in our understanding of the molecular biology and epidemiology of CMV infection and in our ability to diagnosis and treat CMV disease, it remains a major cause of morbidity but is no longer a major cause of mortality after liver transplantation. Risk factors for CMV disease after liver transplantation include donor and recipient serologic status, the use of antilymphocyte therapy, and retransplantation. CMV disease occurs early after transplantation, and the most frequent site of disease is the hepatic allograft. We have treated 79 patients with intravenous ganciclovir, with ultimate control of disease achieved in 69 patients (87.3%). Preliminary results using intravenous immunoglobulin and oral acyclovir for CMV prophylaxis in high-risk patients have been encouraging. In addition to producing clinical syndromes, CMV may have direct immunologic effects and is a marker of the net state of immunosuppression.     

Surveillance of cytomegalovirus infection in haematopoietic stem cell transplantation patients

OBJECTIVES: The aim of this study was to describe our experience in the control of active CMV infection following HSCT using two strategies of CMV infection treatment: ganciclovir universal prophylaxis at low doses and pre-emptive therapy with ganciclovir. METHODS: The surveillance was based on the monitoring of antigenaemia (AGM) and on a nested polymerase chain reaction (N-PCR) for the detection of CMV in both strategies. Forty-five recipients with malignant diseases and with a risk for CMV disease received universal prophylaxis (Group A). The non-treated group consisted of 24 patients, most of them with non-malignant diseases who did not receive universal prophylaxis (Group B). RESULTS: In Group A, the incidence of positive AGM was 51%, with a positive PCR of 68.9%. In Group B, the AGM positivity was 66.7% and that of N-PCR was 66.7%. CMV disease occurred in 6/55 patients (10.9%), with 2/36 (5.5%) from Group A and 4/19 (21%) from Group B. Two of these six patients (33.3%) died of CMV disease. CONCLUSIONS: Our result suggests that AGM and N-PCR can be used as markers for assessing the monitoring and the introduction pre-emptive therapy. This approach could prove to be more cost-effective than ganciclovir universal prophylaxis for treating CMV infection.     

Risk factors for late cytomegalovirus infection after allogeneic stem cell transplantation using HLA-matched sibling donor: donor lymphocyte infusion and previous history of early CMV infection

An increased incidence of late cytomegalovirus (CMV) infection has been reported during the last decade since the introduction of ganciclovir (GCV) prophylaxis or GCV pre-emptive therapy. Given that a donor lymphocyte infusion (DLI) can induce more severe GVHD, this may predispose a patient to late CMV infection. In all, 64 patients (median age 36, M/F 38/26) underwent allogeneic stem cell transplantation (SCT) using a matched sibling donor with bone marrow (n=9) or peripheral blood stem cells (n=55). The overall incidence of CMV infection, early and late CMV infection was 46.9 (30/64), 42.2 (27/64), and 16.4% (9/55), respectively. Early CMV infection was treated with GCV pre-emptive therapy that produced a 92.6% success rate. Among the 20 patients who received 35 DLIs, late CMV infection developed in eight (42.1%) of 19 evaluable cases with a median onset at 127 days post transplant. Risk factors for late CMV infection in a logistic regression analysis included DLIs (P=0.001) and a previous history of CMV infection (P=0.006). In conclusion, late CMV infection was strongly associated with DLIs and a previous history of early CMV infection. Accordingly, extended surveillance of CMV antigenemia is recommended for patients receiving DLIs or who have a previous history of CMV infection.     

Diagnostic approaches to cytomegalovirus infection in bone marrow and organ transplantation

Cytomegalovirus (CMV) continues to be a clinical problem, impairing the overall success rate of transplantation, either through direct involvement of a variety of end-organs or by inducing indirect effects such as graft rejection. We review here how the virus manages to evade host immune responses and replicate extensively in allograft recipients. Recent studies show that the quantity of CMV (viral load) is related directly to the development of CMV disease. We review how clinically significant levels of CMV viral load can be defined and summarize the results of studies showing that a high CMV viral load is the major determinant of CMV disease, explaining the previously reported risk factors of pre-transplant serostatus and the post-transplant detection of CMV viremia. Note     

Cytomegalovirus-specific cellular immune responses and viremia in recipients of allogeneic stem cell transplants

The immune suppression inherent in allogeneic stem cell transplantation (SCT) offers a favorable environment for infection by opportunistic agents, such as human cytomegalovirus (CMV). Despite the application of potent antiviral prophylaxis, patients remain at risk for CMV infection until adequate immunity is restored. CMV-specific CD8(+) T cell counts were monitored, using HLA-A2 tetrameric complexes, to establish the level of immune response to the viral phosphoprotein UL83 in patients after allogeneic SCT. Correlating this with viral replication and clinical status shows that the level of tetramer-positive T cells provides an assessment of CMV immune reconstitution after stem cell transplantation. Most patients with seropositive donors did reconstitute long-term CMV immunity, unless prolonged immunosuppression to control graft-versus-host disease was induced. Together with polymerase chain reaction testing, this technique provides measurable parameters that can be a guide to therapeutic decision making and can form the basis of CMV immunotherapy.     

Antral mass due to cytomegalovirus infection requiring gastrectomy in a liver transplant recipient

Abstract: The incidence of cytomegalovirus (CMV) infection after liver transplantation (LT) has decreased in recent years. Advances in immunosuppression and CMV prophylaxis have improved the management of CMV disease. Organ involvement is infrequent and gastrointestinal CMV disease is quite rare. Few cases of an antral mass due to CMV infection have been described; those reported to date have mostly been in patients with acquired immunodeficiency syndrome. We describe a case of a CMV‐seronegative liver transplant patient who received a seropositive liver graft. Owing to gastrointestinal complaints, CMV prophylaxis was stopped one month after LT. The patient developed an antral mass due to CMV infection and an anastomotic biliary stricture. Antigenemia became negative with ganciclovir, but this treatment did not eliminate the mass. Ganciclovir resistance was ruled out as well as other causes of antral mass, especially malignancy. The patient finally required gastrectomy and hepaticojejunostomy. We conclude that CMV disease is less common today but should be included in the diagnosis of gastrointestinal mass after transplantation.     

Emerging Cytomegalovirus Management Strategies After Solid Organ Transplantation: Challenges and Opportunities

Cytomegalovirus (CMV) remains as one of the most common pathogens after solid organ transplantation (SOT). During the past year, management guidelines were updated, and numerous studies were published—all collectively emphasizing the ongoing efforts to improve management of CMV after SOT. Improvement in laboratory diagnostics was aided by the WHO international calibration standard for nucleic acid testing, which allows for meaningful comparison of viral load values among laboratories. The potential translation of methods for assessing CMV-specific cellular immunity could provide tools for CMV risk assessment and management. Efforts continue to optimize antiviral strategies for CMV disease prevention and treatment. CMV vaccines continue to be tested in various stages of clinical trials. Novel anti-CMV drugs are being developed, including agents that have been used as compassionate therapy for treatment of drug-resistant CMV. In this article, the authors review recent developments on CMV and discuss their implications in CMV management after transplantation.     

Impact of targeted oral ganciclovir prophylaxis for transplant recipients of livers from cytomegalovirus-seropositive donors

OBJECTIVES: Symptomatic cytomegalovirus (CMV) infection can cause significant morbidity and occasional mortality after liver transplantation. In a previous audit, we showed that donor CMV seropositivity (D+) was a risk factor for symptomatic infection, and we estimated the likely clinical and financial impact of 14 weeks of oral ganciclovir prophylaxis given to recipients of CMV-seropositive organs. In August 2001, we adopted this policy of targeted oral ganciclovir prophylaxis for recipients of CMV-seropositive livers. METHOD: The additional costs of adopting targeted prophylaxis policy for 1 year, patient and doctor compliance with the new strategy, and its clinical impact were analysed. RESULTS: Targeted prophylaxis reduced the incidence of symptomatic CMV infection from 9.5% (in the earlier cohort that did not receive prophylaxis) to 5.8% (P = NS). Symptomatic infection was not observed in CMV-seropositive recipients of CMV-seropositive donor livers (P = 0.06 for comparison of the 2 cohorts), but the incidence of symptomatic infection in the CMV-seronegative recipients of CMV-seropositive organs did not change. However, symptomatic infection appeared to be less severe and was delayed by ganciclovir prophylaxis (median time from transplantation to symptom onset 96 vs. 39 days without prophylaxis). Death attributable to CMV infection was not observed in the cohort that received prophylaxis. The additional cost associated with implementation of the prophylaxis strategy was 108,068 pounds sterlings. CONCLUSION: Targeted CMV prophylaxis with oral ganciclovir reduces the incidence and severity of symptomatic infection and appears to be a cost-effective means of improving outcome following liver transplantation.