Management Of Liver Transplant Recipients Research Articles

An overview of unresolved issues in the perioperative management of liver transplant patients.

Over the past decade, the field of solid organ transplantation has undergone significant changes, with some of the most notable advancements occurring in liver transplantation. Recent years have seen substantial progress in preoperative patient optimization protocols, anesthesia monitoring, coagulation management, and fluid management, among other areas. These improvements have led to excellent perioperative outcomes for all surgical patients, including those undergoing liver transplantation. In the last few decades, there have been numerous publications in the field of liver transplantation, but controversies related to perioperative management of liver transplant recipients persist. In this review article, we address the unresolved issues surrounding the anesthetic management of patients scheduled for liver transplantation.

Main factors influencing long-term outcomes of liver transplantation in 2022.

Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.

Indocyanine green clearance test in liver transplantation: defining cut-off levels for graft viability assessment during organ retrieval and for the prediction of post-transplant graft function recovery - the Liver Indocyanine Green (LivInG) Trial Study Protocol

IntroductionViability assessment of the graft is essential to lower the risk of liver transplantation (LT) failure and need for emergency retransplantation, however, this still relies mainly on surgeon’s experience. Post-LT...

Pregnancy Outcomes After Liver Transplantation: A Systematic Review and Meta-Analysis.

Liver transplantation (LT) remains the gold standard for treatment of end-stage liver disease. Given the increasing number of liver transplantation in females of reproductive age, our aim was to conduct a systematic review and meta-analysis evaluating pregnancy outcomes after LT. MEDLINE, Embase, and Scopus databases were searched for relevant studies. Study selection, quality assessment, and data extraction were conducted independently by 2 reviewers. Estimates of pregnancy-related outcomes in LT recipients were generated and pooled across studies using the random-effects model. A comprehensive search identified 1,430 potential studies. Thirty-eight studies with 1,131 pregnancies among 838 LT recipients were included in the analysis. Mean maternal age at pregnancy was 27.8 years, with a mean interval from LT to pregnancy of 59.7 months. The live birth rate was 80.4%, with a mean gestational age of 36.5 weeks. The rate of miscarriages (16.7%) was similar to the general population (10%-20%). The rates of preterm birth, preeclampsia, and cesarean delivery (32.1%, 12.5%, and 42.2%, respectively) among LT recipients were all higher than the rates for the general US population (9.9%, 4%, and 32%, respectively). Most analyses were associated with substantial heterogeneity. Pregnancy outcomes after LT are favorable, but the risk of maternal and fetal complications is increased. Large studies along with consistent reporting to national registries are necessary for appropriate patient counseling and to guide clinical management of LT recipients during pregnancy.

Current Challenges in the Post-Transplant Care of Liver Transplant Recipients in Germany.

Improving long-term patient and graft survival after liver transplantation (LT) remains a major challenge. Compared to the early phase after LT, long-term morbidity and mortality of the recipients not only depends on complications immediately related to the graft function, infections, or rejection, but also on medical factors such as de novo malignancies, metabolic disorders (e.g., new-onset diabetes, osteoporosis), psychiatric conditions (e.g., anxiety, depression), renal failure, and cardiovascular diseases. While a comprehensive post-transplant care at the LT center and the connected regional networks may improve outcome, there is currently no generally accepted standard to the post-transplant management of LT recipients in Germany. We therefore described the structure and standards of post-LT care by conducting a survey at 12 German LT centers including transplant hepatologists and surgeons. Aftercare structures and form of cost reimbursement considerably varied between LT centers across Germany. Further discussions and studies are required to define optimal structure and content of post-LT care systems, aiming at improving the long-term outcomes of LT recipients.

Clinical Relevance of Kidney Biopsy in Patients Qualified for Liver Transplantation and After This Procedure in the Model for End-stage Liver Disease (MELD) Era: Where Are We Today?

Chronic kidney disease (CKD) has been recognized as an increasingly common complication of liver transplantation (OLTx). Post-transplant renal dysfunction contributes to long-term morbidity and mortality following OLTx and is a very important issue in the management of liver transplant recipients. Its etiology is multifactorial and can be determined by kidney biopsy, which is too rarely done in this patient group. In the clinical context of patients with liver cirrhosis, accurate and reliable evaluation of the renal injury is crucial.We performed a review of kidney biopsies in patients with symptoms of CKD (proteinuria/hematuria/elevated creatinine) before and after liver transplantation in the published literature.Kidney biopsies were performed either before or after liver transplantation using percutaneous technique. There are few reports on transjugular kidney biopsy. Biopsy results prevented unnecessary modification of immunosuppressive therapy or selection of candidates for liver transplantation.In our opinion, kidney biopsy is a clinically relevant diagnostic approach to recognize kidney disease before and after liver transplantation, it also helps with the management of kidney disease in this population, and it is safe. Kidney biopsy should be offered more often in liver transplant patients to ensure appropriate therapy in concomitant CKD in this population. Our decisions today will impact clinical outcomes in the future.

Splanchnic and systemic circulation cross talks: Implications for hemodynamic management of liver transplant recipients.

The interaction between splanchnic and systemic circulation has many hemodynamic and renal consequences during liver transplant. In a patient with liver cirrhosis, splanchnic vasodilatation causes arterial steal from the systemic circulation into the splanchnic bed, which decreases the effective blood volume. Moreover, rapid volume loading in these patients has less impact on the cardiac output because a higher proportion of infused fluid is shifted to the splanchnic area. Thus, in dissection phase, the traditional approach of volume loading to maintain intraoperative hemodynamic stability not only seems ineffective, but it may also aggravate surgical bleeding. Two approaches of volume therapy have been mentioned to maintain hemodynamic stability during liver transplantation: splanchnic volume reduction by volume restriction with or without phlebotomy to maintain low central venous pressure (CVP), and splanchnic decongestion using splanchnic vasoconstrictors. After reperfusion, an increase in the central blood volume was thought to have a deleterious effect on the new graft function; however, the precise central venous pressure value that causes hepatic congestion after reperfusion is unknown.

Intraoperative anesthetic management of the liver transplant recipient with portopulmonary hypertension.

Liver transplantation in patients with portopulmonary hypertension (POPH) is associated with increased perioperative risk. Important recent advances in the management of liver transplantation recipients with POPH are discussed. The presence of POPH at the time of liver transplantation should not be a contraindication for liver transplantation, as POPH is common and may be related to volume overload and/or high cardiac output (CO). Available data suggest that patients with mild POPH (25-35 mmHg) can safely undergo liver transplantation surgery. In more severe cases, treatment of POPH with a combination of vasoactive drugs may lead to successful liver transplantation with normalization of POPH. The key to successful intraoperative anesthetic management is maintaining the right ventricular preload and avoiding right ventricular dysfunction. Techniques include diuresis, intraoperative hemodialysis, venovenous bypass, or extracorporeal membrane oxygenation. Apart from the surgical and anesthetic techniques used, factors that contribute to increased pulmonary vascular resistance have to be avoided and the continuation of the vasodilators into the intraoperative and postoperative periods is crucial. The current article provides a review of the current challenges and advances in the management of liver transplantation recipients with POPH from the anesthetic point of view.

Liver Transplant Immunology 2: Application to Liver Allograft Immunity

The liver is a multifunctional organ responsible for complex metabolic and immune functions. Although not a classic lymphoid organ, the liver is enriched with traditional immune cells as well as parenchymal and nonparenchymal cells that play a key role in immune homeostasis. Due to its location and unique anatomic structure, the liver must finely balance immunity and tolerance to avoid undue inflammation in the setting of constant antigenic exposure from portal blood flow while maintaining appropriate immunity against pathogens. Since the first successful liver transplantation in humans in 1967 at the University of Colorado, our knowledge of hepatic immunity and tolerance, in the context of both liver disease and liver transplantation, has evolved dramatically. With these advancements, therapeutic modalities have been developed that have revolutionized the care of liver transplant recipients. In Part 2: Application to Liver Allograft Immunity, we apply the basic principles of liver immunology and allorecognition to our current management of liver transplant recipients in the context of both immunosuppression and the holy grail of transplantation, operational tolerance. This review contains 4 figures, 3 tables, and 32 references Key Words: adaptive immunity; allograft rejection; allograft tolerance; allorecognition; antigen presenting cells; immunosuppression; innate immunity; liver transplantation; T lymphocytes

Management of the critically ill liver failure patient: surpassing our limitations to reach transplantation.

Patients with liver failure and liver-related diseases are often critically ill. Here, we review advances in donor organ management, tools for patient selection and highlight ICU management of liver transplant (LT) recipients. A focused discussion on the impact each of these factors have on critical care management of liver failure patients is presented. Artificial liver assist devices to increase donor organ utilization are broadening the potential for transplantation of critically ill patients. Additionally, prognostication tools continue to improve and identify patients salvageable with transplantation despite severely deranged physiology. Most importantly, early recognition of liver failure combined with proactive critical care management reduces the incidence of failure-to-rescue and increases the likelihood of transplantation. Liver transplantation is often the only hope for cure, and despite the presence of profound physiologic disturbances surgery remains the goal. In this review, we cover topics key in ICU management of LT recipients. A focused discussion on development of artificial liver assist devices to increase donor organs, prognostic scoring systems to define appropriate transplant recipients, critical care management of liver failure physiology, and bridging modalities and supportive measures are presented.

Intraoperative management of liver transplant recipients having severe renal dysfunction: results of 42 cases.

PurposeWhereas continuous renal replacement therapy (CRRT) has been utilized during liver transplantation (LT), there was a lack of evidence to support this practice. We investigated the adverse events at the perioperative periods in recipients of LT who received preoperative CRRT without intraoperative CRRT.MethodsWe retrospectively reviewed medical records of adult patients (age ≥ 18 years) who received LT between December 2009 and May 2015. Perioperative data were collected from the recipients, who received preoperative CRRT until immediately before LT, because of refractory renal dysfunction.ResultsOf 706 recipients, 42 recipients received preoperative CRRT. The mean (standard deviation) Model for end-stage liver disease score were 49.6 (13.4). Twenty-six point two percent (26.2%) of recipients experienced the serum potassium > 4.5 mEq/L before reperfusion and treated with regular insulin. Thirty-eight point one percent (38.1%) of recipients were managed with sodium bicarbonate because of acidosis (base excess < −10 mEq/L throughout LT). All patients finished their operations without medically uncontrolled complications such as severe hyperkalemia (serum potassium > 5.5 mEq/L), refractory acidosis, or critical arrhythmias. Mortality was 19% at 30 day and 33.3% at 1 year.ConclusionAlthough intraoperative CRRT was not used in recipients with severe preoperative renal dysfunction, LT was safely performed. Our experience raises a question about the need for intraoperative CRRT.

Quality of life and adherence in liver transplant recipients.

The assessment of quality of life (QoL) after transplantation represents an ancillary tool to evaluate the efficacy of solid organ transplantation, in addition to graft and patient survival rates and complication. The global assessment of QoL after transplantation usually confirms the improvement when compared to pre-transplant setting. However, whereas significant improvement in physical activity has been widely reported, several studies have demonstrated that social domain and cognitive function do not reach the level of general population after surgery. Post-transplant adherence depends on several factors, including patient personality, level of education, understanding of disease, complexity of medical prescriptions, family support. The evaluation of post-transplant adherence includes adherence to medical prescriptions, in particular to immunosuppressive regimens. QoL and adherence represent crucial issues in the long-term management of liver transplant recipients. Therefore, the transplant professionals should be able to identify risk factors of poor adherence and limited quality of life, in adult and pediatric liver transplant recipients.

Abdominal emergencies after liver transplantation: Presentation and surgical management.

With an increasing number of liver transplantation (LT) and an enhanced overall survival, LT recipients are more likely to be admitted in emergency departments of general hospitals. Yet, in LT recipients, common but also benign symptoms may reveal a LT-related (or not) severe condition. To improve management of LT recipients by emergency physicians and general surgeons and potentially improve long-term outcomes, a clinical review was performed. Overall, CT scan and blood tests should be systematically performed. Immunosuppressive side effects should be excluded using blood tests. LT-related complications are more likely to occur during the first three months after LT, including mainly bile leak, arterial aneurysm, and pseudoaneurysm. Patients should be referred in emergency to tertiary centers. Non-LT-related complications and common abdominal conditions may also be diagnosed in LT recipients. Except in case of diffuse peritonitis or in hemodynamically unstable patients when surgical procedure should be performed, most conditions should be reassessed regarding the immunosuppressive treatment and the adhesive abdominal cavity.

Long-term management of liver transplant recipients: A review for the internist.

Outcomes and long-term survival rates after liver transplantation have significantly improved over the last 5 decades, but the improved longevity is accompanied by long-term complications such as metabolic syndrome, obesity, cardiovascular disease, cancer, and bone disease. After the first year, the primary care physician assumes a greater role and provides most of the patient's care. This review provides a source for primary care physicians in managing the long-term medical complications seen in these patients.

National assessment of early biliary complications after liver transplantation: economic implications.

Despite improvement in surgical technique and medical management of liver transplant recipients, biliary complications remain a frequent cause of posttransplant morbidity and graft loss. Biliary complications require potentially expensive interventions including radiologic procedures and surgical revisions. A national data set linking transplant registry and Medicare claims data for 12,803 liver transplant recipients was developed to capture information on complications, treatments, and associated direct medical costs up to 3 years after transplantation. Biliary complications were more common in recipients of donation after cardiac death compared to donation after brain death allografts (23% vs. 19% P<0.001). Among donation after brain death recipients, biliary complications were associated with $54,699 (95% confidence interval [CI], $49,102 to $60,295) of incremental spending in the first year after transplantation and $7,327 in years 2 and 3 (95% CI, $4,419-$10,236). Biliary complications in donation after cardiac death recipients independently increased spending by $94,093 (95% CI, $64,643-$124,542) in the first year and $12,012 (95% CI, $-1,991 to $26,016) in years 2 and 3. This national study of biliary complications demonstrates the significant economic impact of this common perioperative complication and suggests a potential target for quality of care improvements.

The combination of MELD score and ICG liver testing predicts length of stay in the ICU and hospital mortality in liver transplant recipients.

BackgroundEarly prediction of outcome would be useful for an optimal intensive care management of liver transplant recipients. Indocyanine green clearance can be measured non-invasively by pulse spectrophometry and is closely related to liver function.MethodsThis study was undertaken to assess the predictive value of a combination of the model of end stage liver disease (MELD) score and early indocyanine plasma disappearance rates (ICG-PDR) for length of stay in the intensive care unit (ICU), length of stay in the hospital and hospital mortality in liver transplant recipients.ResultsFifty consecutive liver transplant recipients were included in this post Hoc single-center study. ICG-PDR was determined within 6 hours after ICU admission. Endpoints were length of stay in the ICU, length of hospital stay and hospital mortality. The combination of a high MELD score (MELD >25) and a low ICG-PDR clearance (ICG-PDR < 20%/minute) predicts a significant longer stay in the ICU (p = 0.004), a significant longer stay in the hospital (p < 0.001) and a hospital mortality of 40% vs. 0% (p = 0.003).ConclusionThe combination of MELD scores and a singular ICG-PDR measurement in the early postoperative phase is an accurate predictor for outcome in liver transplant recipients. This easy-to-assess tool might be valuable for an optimal intensive care management of those patients.

Immunosuppression Based on Everolimus in Liver Transplant Recipients With Severe Early Post-transplantation Neurotoxicity

The immunosuppressive management of liver transplant recipients suffering early calcineurin inhibitor–induced neurotoxicity is a challenge in daily clinical practice. We have assessed the use of everolimus as the main immunosuppressant in patients presenting severe neurotoxicity in the early post-transplantation period. From October 1988 to October 2012, 10 patients in our center received everolimus because of severe neurotoxicity in the 1st 3 months after transplantation. We analyzed several variables associated with this treatment, including patient characteristics, time from liver transplantation to conversion to everolimus, immunosuppression regimens before and after conversion, treatment efficacy, adverse events, and discontinuation after conversion. Median follow-up after conversion to everolimus was 27 months (range, 1–63 mo). Neurotoxic events were: akinetic mutism in 4 patients, repeated convulsions in 3, cerebrovascular accident in 1, Guillain-Barré syndrome in 1, and disabling tremor in 1. Treatment with calcineurin inhibitors was discontinued in all patients. Post-conversion regimens consisted of everolimus plus mycophenolate mofetil (MMF) plus steroids in 7 patients, everolimus plus MMF in 1, everolimus plus steroids in 1, and everolimus alone in 1. Liver function was maintained for ≥1 month in all patients except 1, who presented a severe rejection that was treated with steroid bolus and Neoral cyclosporine. Neurologic function was fully recovered in 8 patients. In 1 patient with akinetic mutism and another with convulsions, tacrolimus was reintroduced at 2 months and 1 month, respectively, after resolution of the neurotoxic event. Everolimus is feasible and effective as the main immunosuppressant in patients suffering severe neurotoxicity during the 1st 3 months after transplantation. It allows neurologic function to be recovered while maintaining adequate liver function.

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 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 such occurrence of late-onset 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.

Dietitians' practices and perspectives on nutrition priorities for liver transplant recipients

AbstractAimTo describe current practice and priorities of dietitians during the acute (≤3 months) and long‐term (≥6 months) management of liver transplant recipients.MethodsTen liver transplant dietitians (10/14, 71%) in Australia, New Zealand, UK and USA responded to an online survey. The survey graded nutrition priorities on a Likert scale, recorded barriers to service delivery and workforce allocation for nutrition services (ratio of full‐time equivalent: annual transplant rate).ResultsJust over half (n = 6, 60%) reported routine dietary assessment post‐liver transplant. The majority (90%, n = 9) also provide initial dietary education in the acute setting. Thirty percent (n = 3) routinely provide ongoing acute follow up; however, no sites provide routine follow up after 6 months. Dietitian‐to‐transplant patient ratios demonstrated a broad range of resource allocation across sites 1:244 (1:39–1:1410). 70% (n = 7) reported lack of funding as a major barrier. Protein and energy requirements (n = 10, 100%) were identified as the main clinical focus in the acute period. Prevention of post‐transplant weight gain and diabetes were identified as priority areas during the acute period by 60% of respondents (n = 6) and long‐term management by all respondents (n = 10, 100%).ConclusionThis international survey identified inconsistent resourcing of nutrition services post‐liver transplantation, with lack of funding the main barrier to providing long‐term care. While the majority of liver transplant dietitians prioritise prevention of excessive weight gain, long‐term follow up is limited. Further research is needed to investigate the optimal management of liver transplant recipients.

Living donor liver transplantation for patients immunized against human leukocyte antigen

The clinical features and perioperative management of liver transplant recipients who are already sensitized against human leukocyte antigen (HLA) prior to transplantation are not yet clear. Medical records of living donor liver transplant recipients were reviewed and clinical features of the patients possessing anti-HLA antibodies were studied. Among the 470 consecutive living donor liver transplant recipients, 6 patients (1.3%) had preformed anti-HLA antibodies. A review of the postoperative courses of these patients revealed that the problems included platelet transfusion refractoriness (PTR) due to immune-mediated destruction of platelet and thrombotic microangiopathy (TMA). PTR was observed in patients with anti-HLA class I antibodies and only HLA-matched platelet concentrate (HLA-matched PC) relieved thrombocytopenia. Intravenous gammaglobulin had an additive effect to HLA-matched PC in some cases, and platelet transfusion from close relatives might be a substitute for HLA-matched PC in life-threatening situations. Although the etiology of TMA is unremarkable, the incidence was high (67%, 4/6) compared with that in patients who were not sensitized against HLA (5.6%, 26/464; p < 0.01). Of the four patients, three were complicated with late-onset TMA. Considering these clinical features, careful preparation and postoperative management are needed for liver transplant candidates with anti-HLA antibodies.