Lung transplant infection

Lung transplantation has become an accepted therapeutic procedure for the treatment of end‐stage pulmonary parenchymal and vascular disease. Despite improved survival rates over the decades, lung transplant recipients have lower survival rates than other solid organ transplant recipients. The morbidity and mortality following lung transplantation is largely due to infection‐ and rejection‐related complications. This article will review the common infections that develop in the lung transplant recipient, including the general risk factors for infection in this population, and the most frequent bacterial, viral, fungal and other less frequent opportunistic infections. The epidemiology, diagnosis, prophylaxis, treatment and outcomes for the different microbial pathogens will be reviewed. The effects of infection on lung transplant rejection will also be discussed.     

Cardiovascular risk,atherosclerosis and metabolic syndrome after liver transplantation: a mini review

Liver transplantation is the standard of care for acute and chronic end-stage liver disease. Advances in medical therapy and surgical techniques have transformed the long-term survival of liver-transplant (LT) recipients. The prevalence of post-transplant cardiovascular complications has been rising with increased life expectancy after liver transplantation. Currently, deaths related to cardiovascular complications are one of the main causes of long-term mortality in LT recipients, as cardiovascular disease is the reason of 19–42% of non-liver-related mortality after transplant. On the other hand, metabolic syndrome is common among LT recipients before and after transplantation. In fact, their components (abdominal obesity, diabetes mellitus, hypertension and dyslipidemia) are often exacerbated by transplant-specific factors, such as immunosuppression, inappropriate diet, smoking and a sedentary lifestyle, and add a significant risk of developing atherosclerosis. These aspects are discussed in this article.     

Late primary cytomegalovirus infection presenting with acute inflammatory demyelinating polyneuropathy in a heart transplant recipient: a case report and review of the literature

Cytomegalovirus (CMV) infection is well recognized as a cause of morbidity and mortality in heart transplant recipients. Primary CMV infection can occur early post transplant in at‐risk recipients with donor‐derived infection, or any time after transplantation in community‐acquired infection. We describe a unique case of primary CMV infection occurring 14 years after cardiac transplantation. In addition to end‐organ CMV disease, this patient developed a post‐infectious neurologic phenomenon, acute inflammatory demyelinating polyneuropathy. This entity has rarely been reported in the solid organ transplant population.     

Cardiovascular risk factors following orthotopic liver transplantation: predisposing factors,incidence and management

Background: Liver transplantation is the standard of care for acute and chronic causes of end‐stage liver disease. Advances in medical therapy and surgical techniques have led to improvement of patient and graft survival rates following orthotopic liver transplantation. However, the prevalence of post‐transplant cardiovascular complications has been rising with increased life expectancy after liver transplantation. Aims: To determine the incidences, risk factors, and treatment for hypertension, hyperlipidaemia, diabetes, and obesity in the post‐liver transplantation population. Methods: We performed a review of relevant studies available on the PubMed database that provided information on the incidence, risk factors and treatment for cardiovascular complications that develop in the post‐liver transplantation population. Results: Current immunosuppressive agents have improved patient and graft survival rates. However, long‐term exposure to these agents has been associated with development of systemic and metabolic complications including hypertension, hyperlipidaemia, diabetes mellitus and obesity. Cardiovascular disease remains one of the most common causes of death in liver transplant patients with functional grafts. Conclusions: Liver transplant recipients have a higher risk of cardiovascular complications compared with the nontransplant population. Post‐transplant cardiac risk stratification and aggressive treatment of cardiovascular complications, including modification of risk factors and tailoring of immunosuppressive regimen, is imperative to prevent serious complications.     

Hepatitis C infection in transplantation

This review emphasizes the role of HCV in the transplant setting. Prolonged HCV infection results in end-stage liver disease and as such represents a common indication for liver transplantation. Recurrence of infection is almost universal after transplantation in those with viremia before transplantation. Acquired disease is uncommon but nevertheless important, particularly in organ populations in whom screening for infection is not routine. The natural history of post-transplantation disease suggests that the effect on graft or patient survival is minor, at least during short-term follow-up. Long-term follow-up is needed, as well as more detailed study of the factors contributing to severity of post-transplantation disease. Kidney transplant recipients are commonly infected with HCV prior to transplantation. HCV infection after transplantation is associated with an increased risk of liver disease and infectious complications, but its effect on survival is still controversial. Similarly, observations in recipients of other solid organ transplants, such as heart and lung, and bone marrow patients suggest that HCV infection usually is not a major cause of mortality in the first 5 to 10 years of follow-up. Many issues still need to be addressed. The most important is the identification of factors that contribute to disease progression. Finally, effective therapies to eradicate infection and prevent disease progression are awaited.     

Diabetes and cardiovascular disease following kidney transplantation

Kidney transplantation is being performed more frequently for individuals with end stage renal disease (ESRD) due to improved survival and quality of life compared to long-term dialysis. Though rates decrease after transplant, cardiovascular disease (CVD) remains the most common cause of death after kidney transplant. New-onset diabetes after transplant (NODAT), a common complication following kidney transplantation, and pre-transplant diabetes both significantly increase the risk for CVD. Several other risk factors for CVD in kidney transplant recipients have been identified; however, optimal therapy for controlling the risk factors of CVD after kidney transplantation, including NODAT and pre-transplant diabetes, is not well defined. In the following review we will discuss the role of traditional and non-traditional risk factors in CVD after kidney transplant and the mechanisms involved therein. We will also examine the current literature regarding treatment of these risk factors for the prevention of CVD. Finally, we will review the current recommendations for pre- and post-transplant cardiovascular evaluation and management.     

Cardiovascular mortality in liver and kidney transplant recipients: A retrospective analysis from a single institution

Previous studies have demonstrated cardiovascular causes to be among the leading causes of death after liver (LT) and kidney transplantation (KT). Although both recipient populations have unique pre-transplant cardiovascular burdens, they share similarities in post-transplant exposure to cardiovascular risk factors. The aim of this study was to compare cardiovascular mortality after LT and KT.We analyzed causes of death in 370 consecutive LT and 207 KT recipients from in-hospital records at a single tertiary transplant center. Cardiovascular causes of death were defined as cardiac arrest, heart failure, pulmonary embolism, or myocardial infarction.After a median follow-up of 36.5 months, infection was the most common cause of death in both cohorts, followed by cardiovascular causes in KT recipients and graft-related causes in LT recipients in whom cardiovascular causes were the third most common. Cumulative incidence curves for cardiovascular mortality computed with death from other causes as the competing risk were not significantly different (P = .36). While 1-year cumulative cardiovascular mortality was similar (1.6% after LT and 1.5% after KT), the estimated 4-year probability was higher post-KT (3.8% vs. 1.6%). Significant pre-transplant risk factors for overall mortality after KT in multivariable analysis were age at transplantation, left ventricular ejection fraction <50%, and diastolic dysfunction grade 2 or greater, while significant risk factors for cardiovascular mortality were peripheral artery disease and left ventricular ejection fraction <50%. In the LT group no variables remained significant in a multivariable model for either overall or cardiovascular mortality.The present study found no significant overall difference in cardiovascular mortality after LT and KT. While LT and KT recipients may have similar early cardiovascular mortality, long-term risk is potentially lower after LT. Differing characteristics of cardiovascular death between these two patient populations should be further investigated.     

Incidence and management of mycobacterial infection in solid organ transplant recipients

Although advances in surgical technique, immunosuppressive regimens, and medical management have led to improved survival and quality of life after solid organ transplantation, infection continues to represent a major cause of morbidity and mortality in transplant recipients. Immunosuppressive therapy after transplantation compromises cell-mediated immunity in particular, leaving the patient at risk for opportunistic as well as routine community-acquired infections. Mycobacterial infection is a rare but important complication of solid organ transplantation, presenting significant risk to the patient and challenges in terms of treatment. The available literature consists predominantly of case reports and institutional experiences. This article examines both Mycobacterium tuberculosis and nontuberculous mycobacterial infection in the transplant setting.     

Respiratory Viral Infections in Pediatric Solid Organ and Hematopoietic Stem Cell Transplantation

Respiratory viruses are common in children, including pediatric recipients of both solid organ transplantation and hematopoietic stem cell transplantation. The prevalence and risk factors in each of these groups are reviewed. Furthermore, associated morbidity and mortality in pediatric transplant recipients with respiratory viral infections are addressed. The literature on specific prevention and treatment options for respiratory syncytial virus, adenovirus, influenza, and other respiratory viruses in pediatric solid organ and hematopoietic stem cell transplant recipients is reported.     

Lungentransplantation

Lung transplantation has become the standard therapy for selected patients with end-stage pulmonary disease who have no other available therapeutic options. Due to the broadening of indications for lung transplantation and a less restrictive selection of candidates, there is an imbalance between the large number of candidates waiting for an organ and the limited donor pool. This fact was addressed by the extension of donor selection criteria and by the development of new strategies for organ management. Because of the high risk of acute and chronic rejection, lung recipients require intensive immunosuppression, which increases the risk of infections. During the 30 years follow-up after the first successful lung transplant, perioperative mortality has been reduced due to the improvement of surgical techniques, organ preservation and medicinal therapy. Whereas infections represent the main cause of death during the first year after transplantation, chronic graft failure is the main problem of long-term survival.     

Nosocomial infections within the first month of solid organ transplantation

Infections remain a common complication of solid organ transplantation. Early postoperative infections remain a significant cause of morbidity and mortality in solid organ transplant (SOT) recipients. Although significant effort has been made to understand the epidemiology and risk factors for early nosocomial infections in other surgical populations, data in SOT recipients are limited. A literature review was performed to summarize the current understanding of pneumonia, urinary tract infection, surgical‐site infection, bloodstream infection, and Clostridium difficult colitis, occurring within the first 30 days after transplantation.     

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991–92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community‐acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre‐intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high‐risk solid organ transplant patients.     

Effects of Smoking on Solid Organ Transplantation Outcomes

Tobacco smoking is the leading preventable cause of death worldwide. Both donor and recipient smoking have been shown to increase graft loss and mortality in solid organ transplant recipients in many studies. Only in lung transplants is smoking a universal contraindication to transplantation. Transplant centers implement different policies regarding smoking recipients and allografts from smoking donors. Due to scarcity of available allografts, the risks of smoking have to be weighed against the risks of a longer transplant waitlist period. Although transplant centers implement different strategies to encourage smoking cessation pre- and post-transplant, not many studies have been published that validate the efficacy of smoking cessation interventions in this vulnerable population. This article summarizes the results of studies investigating prevalence, impact on outcomes, and cessationinterventions for smoking in the transplant population. We report herein a review of the elevated risks of infection, malignancy, graft loss, cardiovascular events, and mortality in solid organ transplant populations.     

Treatment issues surrounding hepatitis C in renal transplantation: a review

Hepatitis C infection is prevalent in candidates for and recipients of solid organ transplants. In the renal transplant population, HCV infection has been shown to decrease long-term patient and graft survival. The outcomes of HCV in recipients of other solid organ transplants are yet to be established and prospective studies will be needed in the future. In the absence of effective and safe antiviral treatment for HCV infection in renal, heart, and lung transplant recipients, the management of these patients remains a challenge and has led to an increased focus on identifying and treating hepatitis C in patients prior to transplantation. Interferon-based therapy for HCV prior transplantation appears to improve outcomes after transplantation. On the other hand, post-transplant interferon therapy is associated with an increased risk of graft rejection. Given the paucity of information on HCV treatment in solid organ transplant recipients, there is a great need for large-scale, multi-centre randomized controlled trials to determine the optimal approach to HCV infection in this population. This article will summarize the current peer-reviewed literature focusing on the efficacy of amantadine, ribavirin and both standard and pegylated interferon in the treatment of chronic hepatitis C in renal, transplant recipients.     

Prevention of cardiovascular disease in adult recipients of kidney transplants

Although advances in immunosuppression, tissue typing, surgery, and medical management have made transplantation a routine and preferred treatment for patients with irreversible renal failure, successful transplant recipients have a greatly increased risk of premature mortality because of cardiovascular disease and malignancy compared with the general population. Conventional cardiovascular risk factors such as hyperlipidaemia, hypertension, and diabetes are common in transplant recipients, partly because of the effects of immunosuppressive drugs, and are associated with adverse outcomes. However, the natural history of cardiovascular disease in such recipients differs from that in the general population, and only statin therapy has been studied in a large-scale interventional trial. Thus, the management of this disease and the balance between management of conventional risk factors and modification of immunosuppression is complex.     

Medical management of the liver transplant recipient

Long-term survival of liver transplant recipients has become the rule rather than the exception. As a result, the medical complications of long-term survival, including atherosclerotic cardiovascular disease, metabolic bone disease, and de novo malignancy, have accounted for an increasing proportion of late morbidity and mortality. Risk factors for these complications begin before transplant and are potentially modifiable but are exacerbated by the requirement for immunosuppressive medications after transplantation. Surveillance and early intervention programs administered by transplant hepatologists and other medical subspecialists may improve long-term outcomes in liver transplant recipients by ameliorating risk factors for atherosclerosis, bone fractures, and cancer.     

Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir.

The natural history of cytomegalovirus (CMV) disease associated with solid organ transplantation has been modified as a result of the widespread use of antiviral prophylaxis. Anecdotal reports have indicated a reduction of CMV disease at the expense of its later occurrence after completion of ganciclovir prophylaxis. The present study investigated the occurrence of CMV disease and its risk factors among 37 liver and kidney transplant recipients with CMV D+/R- status who received oral ganciclovir during the first 100 days posttransplantation. CMV disease occurred in 9 patients (24.3%) at a median of 144 days posttransplantation (range, 95-190 days). Allograft rejection was found to be strongly associated with the occurrence of late-onset CMV disease (risk ratio, 6.6; 95% confidence interval, 1.4-32.1; P=.02). Thus, CMV D+/R- solid organ transplant recipients receiving 3 months of oral ganciclovir who develop allograft rejection during the period of antiviral prophylaxis may benefit from extended and/or enhanced antiviral prophylaxis to prevent late-onset CMV disease.     

Solid,non-skin,post-liver transplant tumors: Key role of lifestyle and immunosuppression management

Liver transplantation has been the treatment of choice for end-stage liver disease since 1983. Cancer has emerged as a major long-term cause of death for liver transplant recipients. Many retrospective studies that have explored standardized incidence ratio have reported increased rates of solid organ cancers post-liver transplantation; some have also studied risk factors. Liver transplantation results in a two to five-fold mean increase in the rate of solid organ cancers. Risk of head and neck, lung, esophageal, cervical cancers and Kaposi’s sarcoma is high, but risk of colorectal cancer is not clearly demonstrated. There appears to be no excess risk of developing breast or prostate cancer. Environmental risk factors such as viral infection and tobacco consumption, and personal risk factors such as obesity play a key role, but recent data also implicate the role of calcineurin inhibitors, whose cumulative and dose-dependent effects on cell metabolism might play a direct role in oncogenesis. In this paper, we review the results of studies assessing the incidence of non-skin solid tumors in order to understand the mechanisms underlying solid cancers in post-liver transplant patients and, ultimately, discuss how to prevent these cancers. Immunosuppressive protocol changes, including a calcineurin inhibitor-free regimen, combined with dietary guidelines and smoking cessation, are theoretically the best preventive measures.     

Treatment of hepatitis C in potential kidney and heart transplant patients

Hepatitis C virus (HCV) is common in certain solid organ transplant recipients, most notably in those undergoing liver or kidney transplantation. Infection typically antedates transplantation but may have been acquired at the time of transplantation via infected blood products or organs. A more rapid and aggressive course of HCV-related infection and liver disease is the major concern in organ transplant recipients compared with immunocompetent patients. HCV-related liver disease is an important cause of morbidity and mortality in patients with end-stage renal disease treated by dialysis or transplantation. The outcome of HCV infection in renal and liver transplant recipients has been extensively investigated, whereas literature on HCV-related liver disease among patients with orthotopic heart transplantation is scanty. This article reviews the literature concerning the treatment of HCV-related liver disease in renal and orthotopic heart transplantation.     

New-onset diabetes after transplantation: risk factors and clinical impact

With improvements in patient and graft survival, increasing attention has been placed on complications that contribute to long-term patient morbidity and mortality. New-onset diabetes after transplantation (NODAT) is a common complication of solid-organ transplantation, and is a strong predictor of graft failure and cardiovascular mortality in the transplant population. Risk factors for NODAT in transplant recipients are similar to those in non-transplant patients, but transplant-specific risk factors such as hepatitis C (HCV) infection, corticosteroids and calcineurin inhibitors play a dominant role in NODAT pathogenesis. Management of NODAT is similar to type 2 diabetes management in the general population. However, adjusting the immunosuppressant regimen to improve glucose tolerance must be weighed against the risk of allograft rejection. Lifestyle modification is currently the strategy with the least risk and the most benefit.