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Current Concepts in Pediatric Liver Transplantation
Abstract
Liver transplantation is the definitive treatment for end-stage liver disease in both children and adults. Advances over the last 2 decades have resulted in excellent patient and graft survival rates in what were previously cases of fatal disorders. These developments have been due to innovations in surgical technique, increased surgical experience, refinements in immunosuppressive regimens, quality improvements in intraoperative anesthetic management, better understanding of the pathophysiology of the liver diseases, and better preoperative and postoperative care. Remarkably, the use of split-liver and living-related liver transplantation surgical techniques has helped mitigate the well-recognized national organ shortage. This review will discuss the major aspects of pediatric liver transplantation as it pertains to indication for transplantation, recipient selection and listing for orthotopic liver transplantation, pre-orthotopic liver transplantation care of children, optimal timing of orthotopic liver transplantation, surgical technical considerations, postoperative care and complications, and patient and graft survival outcomes.
... When a living donor is available, the timing of liver transplant can be easily organized according to recipient status, markedly minimizing wait time and postoperative mortality risk. 16,17 The posttransplant outcomes of pediatric recipients with ALF are generally considered to be poor compared with pediatric recipients with chronic liver disease and adult recipients with ALF. 18,19 We predict that correct timing for liver transplant is one of the most important parameters for survival. ...
... The living-donor liver transplant presents a serious risk to the donor but allows the donor to actively participate in saving the life of a loved one. 16 In patients with ALF, cerebral edema leads to HE, coma, brain herniation, and eventually death; however, in infants and children, symptoms of HE may be subtle. Hepatic encephalopathy may not appear until the terminal stage and may not be essential to the diagnosis of ALF in children. ...
... Coagulopathy may determine hepatocellular failure in children with ALF and can be used to decide whether liver transplant is required. 16,21 Treating infections using wide-spectrum antibiotics is also important for successful outcomes, both before and after transplant. Plasmapheresis has been undertaken in an attempt to improve cerebral and systemic hemodynamics in ALF patients but was not found to significantly affect patient survival. ...
Objectives:
Acute liver failure is a rapidly progressive and life-threatening disease in children, whose clinical features differ from those of adults.
Materials and methods:
This is a review of a single center's experience with pediatric acute liver failure in a region with insufficient deceased donor support. The study is a retrospective review and analysis of 22 pediatric patients with acute liver failure between January 2007 and May 2013.
Results:
The cause of acute liver failure was indeterminate in 45.4% of cases. Listing for liver transplant was required in 72.7% of patients, whereas 27.3% developed spontaneous remission. In the patients placed on the liver transplant wait list, 75% underwent liver transplant and 25% died before undergoing liver transplant. The presence of ascites, high-grade encephalopathy, and laboratory findings including high lactate dehydrogenase and phosphorous levels and international normalized ratio were significant parameters in selecting patients needing liver transplants. All liver transplants were from living donors. One- and 3-year patient survival rates after liver transplant were 75% and 75%. No serious donor complications occurred.
Conclusions:
Living-donor liver transplant may be the only option to save the lives of pediatric patients with acute liver failure, especially in regions with insufficient deceased-donor support. Timely referral to a multidisciplinary transplant center, expedient evaluation of living donors, and appropriate timing of transplant are crucial for a successful outcome.
... Solid-organ transplantation is an established therapy for children with end-stage heart, lung, liver and kidney diseases. [1][2][3] The majority of pediatric transplant recipients survive into adulthood. 1,4 Pediatric liver transplant (LT) has significantly advanced over the past decade. ...
... [14][15][16] The use of calcineurin inhibitors (CNIs) such as tacrolimus (TAC) and cyclosporine A (CsA) result in a dramatic increase of patient and graft survival. 2,17,18 However, this was associated with nephrotoxicity. 2,12,15,[17][18][19][20][21][22] Because children have a greater cumulative exposure to CNIs, they are potentially at greater risk of severe renal dysfunction and end-stage renal disease (ESRD). ...
... 2,17,18 However, this was associated with nephrotoxicity. 2,12,15,[17][18][19][20][21][22] Because children have a greater cumulative exposure to CNIs, they are potentially at greater risk of severe renal dysfunction and end-stage renal disease (ESRD). 13,[23][24][25] Data on the incidence and risk factors of renal dysfunction among pediatric LT recipients are scanty and controversial. ...
The aim of this review is to define the incidence of renal dysfunction among pediatric liver transplant (LT) survivors, to identify the associated risk factors and to outline the therapeutic options. Renal dysfunction is a common problem after pediatric LT. The measured glomerular filtration rate is considered the "gold-standard" for assessment of renal function. Renal dysfunction in pediatric LT recipients is multifactorial. Renal-sparing immunosuppressive strategies are essential to reverse renal dysfunction and to prevent end-stage renal disease.
... Interviewees who were unwilling to participate in the trial said they would only allow a procedure if they were "100% sure that it would work." Ironically, these same parents are awaiting a treatment that does not have a 100% chance of success: post-transplant survival is 90% at one yr (21), and at 10 yr, there is a 12% retransplantation rate due to hepatic artery thrombosis, chronic rejection, or primary graft dysfunction (22). Significant surgical complications include biliary duct complications (11.8% incidence), portal vein thrombosis (5.2% incidence), and hepatic artery thrombosis (7.3% incidence) (21)(22)(23). ...
... Ironically, these same parents are awaiting a treatment that does not have a 100% chance of success: post-transplant survival is 90% at one yr (21), and at 10 yr, there is a 12% retransplantation rate due to hepatic artery thrombosis, chronic rejection, or primary graft dysfunction (22). Significant surgical complications include biliary duct complications (11.8% incidence), portal vein thrombosis (5.2% incidence), and hepatic artery thrombosis (7.3% incidence) (21)(22)(23). Opportunistic infections associated with immune suppression (40% incidence) are also a risk to survival (21). The apparent underestimation of liver transplant risk may be due to connotations of the treatment's status as "standard," and hence a misperception of risk tolerance due to the "known" nature of these risks. ...
... Significant surgical complications include biliary duct complications (11.8% incidence), portal vein thrombosis (5.2% incidence), and hepatic artery thrombosis (7.3% incidence) (21)(22)(23). Opportunistic infections associated with immune suppression (40% incidence) are also a risk to survival (21). The apparent underestimation of liver transplant risk may be due to connotations of the treatment's status as "standard," and hence a misperception of risk tolerance due to the "known" nature of these risks. ...
We examined factors that affect decision-making for families presented with a phase I clinical trial of hepatocyte transplant as a potential alternative to liver transplant for their children among two groups: (i) families who were actually offered enrollment in the hepatocyte trial and; (ii) families whose children had liver transplants before the trial was available. We conducted semi-structured interviews about actual and hypothetical decision-making regarding trial participation and used grounded theory analysis to identify common themes. The most common motivator for participation was decline in the child's health. The most common deterrent was lack of data from prior hepatocyte transplants, particularly when compared with data available about liver transplant. Interviewees' point of comparison for evaluating relative benefits and risks of hepatocyte transplant oscillated between the alternative of doing nothing while waiting for a liver (the relevant alternative) vs. the alternative of getting a liver. These results suggest that families' reluctance to participate may result from misconceptions about severity of the child's disease, underestimating risks of liver transplant, or confusion about the role of hepatocyte transplant in the treatment pathway. Clarification of available treatment alternatives and associated risks as part of informed consent may improve the quality of decision-making regarding trial enrollment.
... Indeed, acute complications requiring biopsy assessment are now uncommon but not negligible (and, subtle), while histologic diagnosis of long-term conditions is more frequently required and may be challenging. To this end, a multidisciplinary approach to PLTx is essential, and pathologists can notably contribute in almost every step of the procedure 9,10 . In particular, pathologists are involved in diagnosing and grading native diseases, evaluating donor organ status and performance, identifying early signs of organ injury and differentiating transplant-related conditions [e.g., acute and chronic rejection, post-transplant lymphoproliferative disorder (PTLD)] from liver native disease recurrence and de novo diseases. ...
... Pediatric conditions leading to PLTx are quite vast and heterogenous but classically distinguished in cholestatic diseases, metabolic and genetic disorders (either hepato-specific or systemic), acute liver failure scenarios (including drug induced liver injury) 16 and primary liver neoplasms (Tab. I, Fig. 1A) 10,[17][18][19] . Adult type conditions such as autoimmune hepatitis (AIH) 20,21 may also impact the pediatric population, while a pathologic condition that is rapidly increasing and concerning pediatric hepatologists is fatty liver disease 22,23 . ...
Pediatric liver transplantation represents a safe and long-lasting treatment option for various disease types, requiring the pathologist's input. Indeed, an accurate and timely diagnosis is crucial in reporting and grading native liver diseases, evaluating donor liver eligibility and identifying signs of organ injury in the post-transplant follow-up. However, as the procedure is more frequently and widely performed, deceptive and unexplored histopathologic features have emerged with relevant consequences on patient management, particularly when dealing with long-term treatment and weaning of immunosuppression.
In this complex and challenging scenario, this review aims to depict the most relevant histopathologic conditions which could be encountered in pediatric liver transplantation. We will tackle the conditions representing the main indications for transplantation in childhood as well as the complications burdening the post-transplant phases, either immunologically (i.e., rejection) or non-immunologically mediated. Lastly, we hope to provide concise, yet significant, suggestions related to innovative pathology techniques in pediatric liver transplantation.
... During transplant Liver transplant surgery has historically been associated with significant intra-operative blood loss. Remarkably, surgical blood loss has greatly decreased, largely due to changes in surgical technique and intra-operative fluid management, rather than changes in coagulation replacement [14]. However, children are at higher risk than adults for massive transfusion during liver transplant [15]. ...
... Kasai procedure), and with the use of reduced sized grafts [15]. Reports of blood loss during pediatric liver transplant are highly variable (median 79 mL kg À1 ; range 4-586 mL kg À1 ) [14]. Adult studies have highlighted the importance of careful intraoperative titration of central venous pressure to reduce bleeding [16]. ...
There has been extraordinary progress over the last half-century in the field of medical transplantation in which tissue, organs, or body parts from one human are placed into another. Solid organ transplants have allowed thousands of children with otherwise devastating inherited or acquired disorders to survive. Depending upon the clinical situation, there are many specific peri-transplant issues that must be carefully addressed to optimize outcomes. Although surgical, immunologic, and infectious concerns are usually in the forefront, important aspects regarding hemostasis frequently arise. The number of solid organs that can be successfully transplanted in children has expanded over the last decades and includes kidney, liver, heart, lung, intestine, pancreas, and thymus. Bleeding complications may occur in the setting of organ failure prior to transplantation, during the surgical procedure, or in the post-transplant setting, and can results in significant morbidity. This report will focus on preventing and managing non-surgical-related bleeding complications in children undergoing liver, heart, kidney transplantation, in whom there are often unique aspects of coagulation to be considered.
© 2015 International Society on Thrombosis and Haemostasis.
... Although the Kasai procedure, a surgical attempt to restore bile flow, can offer provisional respite, it often fails to prevent long-term liver deterioration in most cases [12]. Approximately 20-30% of paediatric patients with biliary atresia undergo hepatic transplants between the ages of 2 and 18 years after the Kasai procedure [13]. In general, primary hepatic transplantation prior to a Kasai procedure is not indicated in biliary atresia unless they show signs of severe hepatic parenchymal impairment, which can include ascites, coagulopathy, or hypoalbuminaemia [5]. ...
Chronic liver disease (CLD) in children poses significant challenges, necessitating timely management to mitigate morbidity and mortality. Liver transplantation (LT) has emerged as a transformative intervention, offering improved long-term survival for paediatric patients with CLD. This review explores the evolving landscape of liver transplantation, focusing on indications and timing considerations. The aetiology of CLD is diverse, encompassing intrahepatic, extrahepatic cholestatic conditions, metabolic diseases, malignancy, and drug-induced liver injury. LT is indicated when children exhibit signs of hepatic decompensation, necessitating a comprehensive evaluation to assess transplant suitability. Indications for LT include biliary atresia, inborn errors of metabolism, hepatocellular carcinoma, and emerging indications such as mitochondrial hepatopathies and acute on chronic liver failure. The timing of transplantation is critical, emphasizing the need for early recognition of decompensation signs to optimise outcomes. Advancements in LT techniques and immunosuppressive therapies have enhanced patient and graft survival rates. Various transplant modalities, including reduced-size LT and living-related LT, offer tailored solutions to address the unique needs of paediatric patients. While LT represents a cornerstone in the management of paediatric CLD, careful patient selection, multidisciplinary collaboration, and ongoing refinements in transplant protocols are imperative for optimizing outcomes and addressing the evolving landscape of paediatric liver disease management.
... Liver transplantation has become the treatment of choice for end stage liver disease and several metabolic disorders (Emre et al. 2012). Innovative surgical techniques, together with advances in immunosuppressive regimens, have improved graft and patient survival, up to 94%, at 3 months' post-liver transplantation; and up to 71% at 10 years postsurgery (Devictor et al. 2013;Kaczor-Urbanowicz et al. 2017). ...
PurposeTo investigate associations between levels of blood parameters used to monitor liver-transplanted children with their salivary levels, and compare the salivary parameters of transplant recipients with those of healthy controls.Methods
Saliva and blood samples from 30 liver transplanted recipients, mean age 11.7 years and saliva from age and sex matched 27 healthy patients were analyzed using a standard complete blood count test.ResultsUric acid and alkaline phosphatase levels correlated significantly between saliva and blood samples in the transplanted subjects. Median salivary sodium level was significantly lower and the median salivary potassium level significantly higher in transplant recipients compared with healthy subjects. No differences were found between the groups in salivary glucose, urea, chloride, total protein, albumin, calcium, phosphorus, uric acid, total bilirubin, alkaline phosphatase, lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), triglycerides, cholesterol, iron, transferrin, glutamic pyruvic transaminase (GPT) and gamma-glutamyltranspeptidase (GGT).Conclusion
Specific correlations of serum and salivary chemistry were found in liver transplant patients. Such information may lead to the development of noninvasive monitoring tools for this population.
... Los resultados finales con el uso de Split para expandir el número de donantes para pacientes pediátricos han sido buenos, siempre que se pueda contar con un equipo experimentado 18. Cabe recalcar que cuando se usa la técnica de donante vivo relacionado los episodios de rechazo son menores y alcanza el 40% durante el primer año de post trasplante 19 . ...
RESUMEN
El Ecuador no contaba con un programa de trasplante hepático infantil y fue un problema de difícil solución para las autoridades de salud, como alternativa terapéutica se imple- mentó un sistema de derivación internacional y los pacientes accedían al trasplante en centros internacionales con la opción del donante vivo relacionado. Actualmente, se encuentra acreditado el primer programa de trasplante infantil que va a generar un cambio importante en el sistema de atenciones, pero es necesario dejar clara todas las normas y regulaciones que involucren la prioridad de los pacientes pediátricos y los aspectos técnicos quirúrgicos que implican la utilización de hígados reducidos.
... Первую же успешную ТП в Европе провел в 1971 г. J.Otte 17-месячному ребенку, причиной трансплантации послужила также билиарная атрезия [1]. В России первая ТП ребенку выполнена в 1997 г. в ФГБУ «Федеральный научный центр трансплантологии и искусственных органов им. ...
... Liver transplant in young children is life-saving for endstage liver disease, yet patients are known to have a high risk of post-operative complications [20,21] . We aimed to determine potentially modifiable perioperative variables that are independently associated with complications post LT. ...
AIM
To determine potentially modifiable predictors of early
outcomes after liver transplantation in children of age
< 3 years.
METHODS
This study was a retrospective chart review including
all consecutive children of age less than 3-years-old
having had a liver transplant done at the Western
Canadian referral center from June 2005 to June 2015.Pre-specified potential predictor variables and primary
and secondary outcomes were recorded using standard
definitions and a case report form. Associations
between potential predictor variables and outcomes
were determined using univariate and multiple logistic
[odds ratio (OR); 95%CI] or linear (effect size, ES;
95%CI) regressions.
RESULTS
There were 65 children, of mean age 11.9 (SD 7.1)
mo and weight 8.5 (2.1) kg, with biliary-atresia in
40 (62%), who had a living related donor [LRD; 29
(45%)], split/reduced [21 (32%)] or whole liver graft
[15 (23%)]. Outcomes after liver transplant included:
ventilator-days of 12.5 (14.1); pediatric intensive care
unit mortality of 5 (8%); re-operation in 33 (51%),
hepatic artery thrombosis (HAT) in 12 (19%), portal
vein thrombosis (PVT) in 11 (17%), and any severe
complication (HAT, PVT, bile leak, bowel perforation,
intraabdominal infection, retransplant, or death) in 32
(49%) patients. Predictors of the prespecified primary
outcomes on multiple regression were: (1) HAT: split/
reduced (OR 0.06; 0.01, 0.76; P = 0.030) or LRD
(OR 0.16; 0.03, 0.95; P = 0.044) vs whole liver graft;
and (2) ventilator-days: surgeon (P < 0.05), lowest
antithrombin (AT) postoperative day 2-5 (ES -0.24;
-0.47, -0.02; P = 0.034), and split/reduced (ES -12.5;
-21.8, -3.2; P = 0.009) vs whole-liver graft. Predictors
of the pre-specified secondary outcomes on multiple
regression were: (1) any thrombosis: LRD (OR 0.10;
0.01, 0.71; P = 0.021) or split/reduced (OR 0.10; 0.01,
0.85; P = 0.034) vs whole liver graft, and lowest AT
postoperative day 2-5 (OR 0.93; 0.87, 0.99; P = 0.038);
and (2) any severe complication: surgeon (P < 0.05),
lowest AT postoperative day 2-5 (OR 0.92; 0.86-0.98; P
= 0.016), and split/reduced (OR 0.06; 0.01, 0.78; P =
0.032) vs whole-liver graft.
CONCLUSION
In young children, whole liver graft and surgeon was
associated with more complications, and higher AT
postoperative day 2-5 was associated with fewer
complications early after liver transplantation.
... Liver transplant in young children is life-saving for endstage liver disease, yet patients are known to have a high risk of post-operative complications [20,21] . We aimed to determine potentially modifiable perioperative variables that are independently associated with complications post LT. ...
AIM
To determine potentially modifiable predictors of early outcomes after liver transplantation in children of age < 3 years.
METHODS
This study was a retrospective chart review including all consecutive children of age less than 3-years-old having had a liver transplant done at the Western Canadian referral center from June 2005 to June 2015. Pre-specified potential predictor variables and primary and secondary outcomes were recorded using standard definitions and a case report form. Associations between potential predictor variables and outcomes were determined using univariate and multiple logistic [odds ratio (OR); 95%CI] or linear (effect size, ES; 95%CI) regressions.
RESULTS
There were 65 children, of mean age 11.9 (SD 7.1) mo and weight 8.5 (2.1) kg, with biliary-atresia in 40 (62%), who had a living related donor [LRD; 29 (45%)], split/reduced [21 (32%)] or whole liver graft [15 (23%)]. Outcomes after liver transplant included: ventilator-days of 12.5 (14.1); pediatric intensive care unit mortality of 5 (8%); re-operation in 33 (51%), hepatic artery thrombosis (HAT) in 12 (19%), portal vein thrombosis (PVT) in 11 (17%), and any severe complication (HAT, PVT, bile leak, bowel perforation, intraabdominal infection, retransplant, or death) in 32 (49%) patients. Predictors of the prespecified primary outcomes on multiple regression were: (1) HAT: split/reduced (OR 0.06; 0.01, 0.76; P = 0.030) or LRD (OR 0.16; 0.03, 0.95; P = 0.044) vs whole liver graft; and (2) ventilator-days: surgeon (P < 0.05), lowest antithrombin (AT) postoperative day 2-5 (ES -0.24; -0.47, -0.02; P = 0.034), and split/reduced (ES -12.5; -21.8, -3.2; P = 0.009) vs whole-liver graft. Predictors of the pre-specified secondary outcomes on multiple regression were: (1) any thrombosis: LRD (OR 0.10; 0.01, 0.71; P = 0.021) or split/reduced (OR 0.10; 0.01, 0.85; P = 0.034) vs whole liver graft, and lowest AT postoperative day 2-5 (OR 0.93; 0.87, 0.99; P = 0.038); and (2) any severe complication: surgeon (P < 0.05), lowest AT postoperative day 2-5 (OR 0.92; 0.86-0.98; P = 0.016), and split/reduced (OR 0.06; 0.01, 0.78; P = 0.032) vs whole-liver graft.
CONCLUSION
In young children, whole liver graft and surgeon was associated with more complications, and higher AT postoperative day 2-5 was associated with fewer complications early after liver transplantation.
... At the end of the procedure, two complete liver grafts can be obtained, most commonly an LLS for a pediatric recipient and the extended right lobe (segment IV-VIII plus I) for a teenager or an adult. Although right (segment V to VIII) and left (segment I to IV) splitting can be done, it did not gain popularity secondary to technical challenges and graft size problems resulting in an increased incidence of primary graft non-function, vascular thrombosis, bile leaks, or sepsis [25]. SLT can be carried out either on the back table (ex vivo splitting) or during the procurement (in situ splitting). ...
... At present, liver transplantation is considered the gold standard treatment for terminal hepatic diseases in children (1). Advances in surgical techniques, intensive care and immunosuppressive therapy allow this complex procedure to be performed in younger and smaller infants. ...
... Опыт стран Европы и Северной Америки в этой области более скромный, что связано в первую очередь с более развитой системой посмертного донорства, и как следствие -развитие программ трансплантации редуцированной печени и SPLITтрансплантации от посмертного донора, трансплантации целой печени от умершего донора-ребенка [29]. Кроме этого, отмечается снижение общего количества родственных трансплантаций печени после 2002 года, когда произошел летальный исход у живого родственного донора [64,68]. ...
Living donor liver transplantation is a highly effective method to help children with end stage liver diseases. Projected success of operation is largely determined at the stage of selection of potential donor. In our review of the literature is presented historical information, are considered «eastern» and «western» way of development of pediatric living donor liver transplantation, are analyzed the ethical and psychosocial aspects of living donor liver transplantation, and also are set out principles and protocols for evaluation potential donors. In addition, the modern views on volumetry of the potential donor liver and on choice of graft type for transplantation, including for children with low weight are presented.
... At the end of the procedure, two complete liver grafts can be obtained, most commonly an LLS for a pediatric recipient and the extended right lobe (segment IV-VIII plus I) for a teenager or an adult. Although right (segment V to VIII) and left (segment I to IV) splitting can be done, it did not gain popularity secondary to technical challenges and graft size problems resulting in an increased incidence of primary graft non-function, vascular thrombosis, bile leaks, or sepsis [25]. SLT can be carried out either on the back table (ex vivo splitting) or during the procurement (in situ splitting). ...
The first successful liver transplantation was carried out in 1967, and the recipient was a pediatric patient. Since then, many challenges have been overcome and, nowadays, 1-year patient survival after liver transplantation is about 90 % in pediatric patient populations. Standardization of surgical technique, development of better immunosuppressive medications, improved understanding of caring for patients with end-stage liver disease, and improvements in anesthesia and intensive care have had a tremendous impact on graft and patient survival. Despite all improvements, challenging issues in pediatric liver transplantation remain. In this article, we address some of these problems.
... Differently from adulthood, recent data estimated that HBV infection together with HCV cause only the 1-4% of all LT in pediatric series. 66,67 The indications for LT in patients with CHB are hepatic decompensation in a patient with established cirrhosis, or HCC. 68 In the United States, about 5-10% of liver transplants are performed for HBV-related liver disease, 69,70 and outcomes have improved in recent years, with disease recurrence being no longer a significant cause of death/graft loss, 68 thanks to the use of HBIg and antiviral agents. ...
Although a rather benign course of chronic hepatitis B virus (HBV) infection during childhood has been described, 3-5% and 0.01-0.03% of chronic carriers develop cirrhosis or hepatocellular carcinoma before adulthood. Considering the whole lifetime, the risk of hepatocellular carcinoma rises to 9-24% and the incidence of cirrhosis to 2-3% per year. The aim of this article is to review the current knowledge regarding the natural history and treatment of chronic hepatitis B in children and to focus on critical aspects and unresolved questions in the management of childhood HBV infection. A literature search was carried out on MEDLINE, EMBASE, and Web of Science for articles published in English in peer-reviewed journals from January 1980 to February 2013. The search terms used included "Hepatitis B virus infection," "children," "HBV," "interferon," "lamivudine," "adefovir," "entecavir," and "tenofovir." Articles resulting from these searches and relevant references cited in the articles retrieved were reviewed. The current goals of therapy are to suppress viral replication, reduce liver inflammation, and reverse liver fibrosis. Therapeutic options for children are currently limited, and the risk for viral resistance to current and future therapies is a particular concern. Based on the data available at this time, it is the consensus of the panel that it is not appropriate to treat children in the immune-tolerant phase or in the inactive carrier state. For children in the immune-active or reactivation phases, liver histology can help guide treatment decisions. Outside of clinical trials, interferon is the agent of choice in most cases; currently, available nucleoside analogs are secondary therapies.
... Introduction Liver transplantation has been established as a therapy for children with end-stage liver disease. Today, 1-y patient survival rates are approximately 90% [1,2]. Despite ethical dilemmas, pediatric liver transplantation with a living donor provides better quality grafts than organs from cadaveric donors. ...
... At present, liver transplantation is considered the gold standard treatment for terminal hepatic diseases in children (1). Advances in surgical techniques, intensive care and immunosuppressive therapy allow this complex procedure to be performed in younger and smaller infants. ...
The ideal ratio between liver graft mass and recipient body weight for liver transplantation in small infants is unknown; however, if this ratio is over 4%, a condition called large-for-size may occur. Experimental models of large-for-size liver transplants have not been described in the literature. In addition, orthotopic liver transplantation is marked by high morbidity and mortality rates in animals due to the clamping of the venous splanchnic system. Therefore, the objective of this study was to create a porcine model of large-for-size liver transplantation with clamping of the supraceliac aorta during the anhepatic phase as an alternative to venovenous bypass.
Fourteen pigs underwent liver transplantation with whole-liver grafts without venovenous bypass and were divided into two experimental groups: the control group, in which the weights of the donors were similar to the weights of the recipients; and the large-for-size group, in which the weights of the donors were nearly 2 times the weights of the recipients. Hemodynamic data, the results of serum biochemical analyses and histological examination of the transplanted livers were collected.
The mortality rate in both groups was 16.5% (1/7). The animals in the large-for-size group had increased serum levels of potassium, sodium, aspartate aminotransferase and alanine aminotransferase after graft reperfusion. The histological analyses revealed that there were no significant differences between the groups.
This transplant method is a feasible experimental model of large-for-size liver transplantation.
BACKGROUND
Liver transplantation (LT) is a life-saving procedure for patients with end-stage
liver disease and has become the standard and most effective treatment method
for these patients. There are many indications for LT that vary between countries
and settings. The outcome of LT depends on the available facilities and surgical
expertise, as well as the types of liver graft donors available.
AIM
To assess the clinical characteristics of patients from Bahrain who underwent LT
overseas, and analyze factors affecting their survival.
METHODS
In this retrospective cohort study, we reviewed the medical records and overseas
committee registry information of all pediatric and adult patients who were sent
overseas to undergo LT by the Pediatric and Medical Departments of Salmaniya
Medical Complex and Bahrain Defence Force Hospital via the Overseas Treatment
Office, Ministry of Health, Kingdom of Bahrain, between 1997 and 2023. Demographic data, LT indication, donor-recipient relationship, overseas LT center, graft type, post-LT medications, and LT complications, were collected. Outcomes measured included the overall and 5-year LT survival rate. Fisher’s exact, Pearson χ2, and Mann-Whitney U tests were used to compare the pediatric and the adults’ group in terms of clinical characteristics, donor-recipient relationship, medication, complications, and outcome. Survival analysis was estimated via the Kaplan-Meier’s
method. Univariate and multivariate analyses were used to detect predictors of survival.
RESULTS
Of the 208 eligible patients, 170 (81.7%) were sent overseas to undergo LT while 38 (18.3%) remained on the waiting list. Of the 170 patients, 167 (80.3%) underwent LT and were included in the study. The majority of the patients were Bahraini (91.0%), and most were males (57.5%). One-hundred-and-twenty (71.8%) were adults and 47 (28.3%) were children. The median age at transplant was 50.0 [interquartile range (IQR): 14.9–58.4] years. The main indication for pediatric LT was biliary atresia (31.9%), while that of adult LT was hepatitis C-related cirrhosis (35.0%). Six (3.6%) patients required re-transplantation. Most patients received a living-related liver graft (82%). Pediatric patients received more living and related grafts than adults (P = 0.038 and P = 0.041, respectively), while adult patients received more cadaveric and unrelated grafts. Most patients required long-term immunosuppressive
therapy after LT (94.7%), of which tacrolimus was the most prescribed (84.0%), followed by prednisolone (50.7%), which was prescribed more frequently for pediatric patients (P = 0.001). Most patients developed complications (62.4%) with infectious episodes being the most common (38.9%), followed by biliary stricture (19.5%). Tonsilitis and sepsis (n = 12, 8.1% for each) were the most frequent infections. Pediatric patients experienced higher rates of infection, rejection, and early poor graft function than adult patients (P < 0.001, P = 0.003, and P = 0.025,
respectively). The median follow-up time was 6.5 (IQR: 2.6–10.6) years. The overall survival rate was 84.4%, the 5-year survival rate, 86.2%, and the mortality rate, 15.6%. Younger patients had significantly better odds of survival (P = 0.019) and patients who survived had significantly longer follow-up periods (P < 0.001).
CONCLUSION
Patients with end-stage liver disease in Bahrain shared characteristics with those from other countries. Since LT facilities are not available, an overseas LT has offered them great hope.
Background:
Liver transplantation (LT) is a treatment modality in the pediatric population for several diseases like biliary atresia, metabolic liver disease, hepatoblastoma, and so on. According to the Organ Procurement and Transplantation Network, 5-year survival was reported as 85.4% to 93.5% by age after pediatric liver transplantation (PLT). This study aimed to evaluate our single-center experience of PLT by analyzing long-term results, comparing the outcomes with the literature, and identifying predictors of patient survival.
Methods:
The data of 40 patients who underwent LT at <18 years of age between June 2015 and June 2021 were studied retrospectively. Recipient characteristics such as age, sex, etiology of liver disease follow-up time, postoperative vascular and biliary complications, and donor characteristics were evaluated.
Results:
There were 20 (50%) girls and 20 (50%) boys, and the median age was 42 (IQR = 9-117) months. The most common indications of LT were biliary disorders (45%). A whole liver graft was used in 7 (17%), a right lobe graft in 9 (23%), a left lobe graft in 4 (10%), and a left lateral lobe graft in 20 (50%) of the recipients. The 1-, 3-, 5-, and 7-year survival rates were 85%, 82.1%, 82.1%, and 82.1%, respectively. The multivariate survival analysis revealed that the pediatric end-stage liver disease score, hepatic artery thrombosis, and portal vein thrombosis are associated with overall mortality.
Conclusion:
In conclusion, our long-term survival is similar to the literature, with satisfactory results. However, reducing the vascular complication rates can provide superior results on PLT.
Liver disease in children is increasing in prevalence, placing a huge burden on healthcare systems and often requiring long-term management. Offering an integrative approach to the science and clinical practice of pediatric hepatology, this is the definitive reference text for improved diagnosis and treatment strategies. In the new edition of this authoritative text, chapters have been thoroughly revised in line with major advances in the field, such as recognizing the increased frequency of fatty liver disease, and how genetic testing has the potential to establish earlier diagnoses for a variety of diseases. Disorders covered include cholestasis, metabolic disorders and hepatitis, with their presentation across the spectrum of infancy, childhood and adolescence discussed. The indications and surgical aspects of liver transplant are explained and post-transplant care is described in detail. This is a valuable resource for pediatricians, hepatologists, gastroenterologists and all clinicians involved in the care of children with liver diseases.
The diagnosis of irreversible intestinal failure confers significant morbidity, mortality, and decreased quality of life. Patients with irreversible intestinal failure may be treated with intestinal transplantation. Intestinal transplantation may include intestine only, liver-intestine, or other visceral elements. Intestinal transplantation candidates present with systemic manifestations of intestinal failure requiring multidisciplinary evaluation at an intestinal transplantation center. Central access may be difficult in intestinal transplantation candidates. Intestinal transplantation is a complex operation with potential for hemodynamic and metabolic instability. Patient and graft survival are improving, but graft failure remains the most common postoperative complication.
The LDLT option in the pediatric population allows recipients to be transplanted early. A total of 202 consecutive pediatric liver transplants from two different institutions-108 (LDLT) and 94 (DDLT)-were retrospectively compared. Overall, one- and three-yr patient and graft survival were similar between DDLT and LDLT. ACR was greater in recipients of DDLT at one and three yr (50.8% and 61.0%) compared to LDLT (30.8% and 32.2%) (p = 0.002). When the data were stratified according to PELD/MELD score, LDLT with a low score had better one- and three-yr graft survival (96.2% and 96.2%) compared to DDLT (88.2% and 85.2%) (p = 0.02), with comparable patient survival (p = 0.75). Patient and graft survival were similar between DDLT and LDLT in the high PELD/MELD group. Lower incidence of ACR in both low and high PELD/MELD groups was (29.6% and 34.3%) for LDLT compared to DDLT (50.3% and 53.3%, p = 0.002 and p = 0.028, respectively). Regardless of PELD/MELD score, status, age group, and recipient weight, LDLT provides excellent patient and graft survival with a lower incidence of rejection compared to DDLT.
The article presents an analysis of modern domestic and foreign literature on the problems of liver transplantation in children and adults. Liver transplantation is performed for more than 50 years and it has become a reliable, rational way, and sometimes the only life-saving treatment for children and adults suffering from diffuse liver disease or unresectable tumors. Currently, the Russian Federation opened 14 centers for liver transplantation (in Moscow, St. Petersburg, Belgorod, Krasnodar, Irkutsk, Novosibirsk, Yekaterinburg and Nizhniy Novgorod), which is performed annually 200-240 operations. Estimated demand for the provision of this service is much higher: 52-64 center, and 2000-2500 operations per year. However, liver transplantation in children performs only in two centers in Moscow. Possibility of timely planning of liver transplantation in children of any age has now become a reality, but with a very limited capacity. Recently there has been improvement in diagnostic capabilities to identify various congenital and acquired diseases of the liver in children requiring liver transplantation. We can already predict the increase in demand for this type of surgery. In the North-Western Federal District is a center in which possible liver transplantation in adults, while the children’s opportunities for transplantation in the region do not have. The reasons leading to liver transplantation in children and adults are different. In adult practice dominated by cirrhosis in the outcome of chronic viral hepatitis B and C, whereas in children biliary atresia and congenital metabolic disorders.
We present here the outcomes of our first 500 liver transplants and discuss the lessons learned during this time.
We retrospectively analyzed the first 500 consecutive transplants within the listing criteria of the United Network for Organ Sharing, with recipients and donors with minimum 1-year follow-up. Patient survival and donor complications were analyzed for 31 liver transplant recipients with hepatocellular carcinoma beyond the Milan criteria who had transplant performed during the same time.
Between August 2006 and March 2013, there were 519 liver transplants performed in 500 patients (365 adult, 135 pediatric). There were 394 living-donor and 125 deceased-donor liver transplants. In addition, 31 adult liver transplants were performed in patients with hepatocellular carcinoma beyond Milan criteria (22 living-donor and 9 deceased-donor transplants). The main cause of chronic liver failure was biliary atresia in pediatric patients (30.4%) and chronic hepatitis B infection in adults (35.6%). The complication rate for primary nonfunction was 3.8%, overall biliary complications 24.0% (significantly higher after adult living-donor liver transplant, 30.3%), hepatic artery thrombosis 1.6%, portal vein thrombosis 3.0%, retransplant 3.8%, acute cellular rejection 29.6%, and bacterial infection 39.4%. Overall 1-, 3-, and 5-year patient survival rates in the first 500 consecutive transplants performed on recipients within United Network for Organ Sharing listing criteria were 87.8%, 85.0%, and 78.6%; for hepatocellular carcinoma patients beyond the Milan criteria, survival rates were 71.9%, 52.5%, and 38.2%.
In regions without a sufficient number of deceased donors, living-donor liver transplant, with its associated problems, is the only alternative to deceased-donor liver transplant. Liver transplant requires teamwork, with all players working well together for a successful outcome. The important keys to success in liver transplant include decision-making, timing, surgical skills, experience, and close follow-up.
Background:
Liver ischemia-reperfusion (I/R) injury is of great importance in primary graft dysfunction after transplantation, and could be more severe in transplantation using aged donor livers. In order to alleviate the I/R injury in aged donor livers, we transferred exogenous human telomerase reverse transcriptase (hTERT) gene into aged rat's livers before liver transplantation. After transplantation, the effect of the gene for aged rats on cell apoptosis caused by I/R injury was evaluated.
Methods:
The experiment was divided into 2 parts: comparative experiment between aged rats and adult rats, and exogenous induction experiment of aged rats. In the first part, Wistar rats were divided into 2 groups; group I was composed of adult rats (5 months) and group II was composed of aged rats (16-18 months). After successful transplantation, chronic oxidative stress and lipid peroxidation-related indicators (contents of vitamin C and vitamin E; activities of superoxide dismutase, catalase, and methane decarboxylic aldehyde) and alanine aminotransferase activity were examined. In the second part, additional aged rats were divided into 3 groups: group A included the donors pretreated with exogenous hTERT gene; group B included the donors pretreated with adenovirus vector; and group C was composed of the donors pretreated with physiological saline. Various indicators were detected to analyze the effect of the gene on I/R injury of the aged rats.
Results:
The lower vitamin C, vitamin E, SOD, and CAT contents in the aged group than those in the adult group (P < .05), and the higher MDA and ALT contents in the aged group than those in the adult group (P < .05) were observed. The apoptotic index and ALT levels in the hTERT gene-pretreated group were significantly lower than those in the adenovirus vector group and the physiological saline group (P < .05). Meanwhile, mild histological injury and increased telomerase activity were also observed in the hTERT gene-pretreated group.
Conclusion:
Compared with the adult rats, I/R injury in the aged liver donor is more severe. The induction of exogenous hTERT gene offers protection against I/R injury in the aged liver.
We describe the medical state of the art in liver, pancreas and small bowel transplantation, and portray the ethical issues. Although most ethical questions related to these transplantations are not specific for liver, pancreas and small bowel, they do challenge ethical analysis as well as new policies and clinical procedures. Firstly, outcomes continue to be of utmost concern, as information is only limited available, is developing over time and is surrounded by many uncertainties. Secondly, characteristics of donors and recipients should be carefully evaluated. The question of what qualifies a donor and a recipient should be considered against the background of a quest for extended criteria, embracing marginal cases, and a judgment with regard to what counts as a good enough outcome. Thirdly, ethical principles of autonomy and fairness are pushed, given the circumstance of severe scarcity, towards limits that can easily be crossed.
Here, we present the outcomes of 100 consecutive pediatric liver transplant patients in our center.
Five hundred fifteen adult and pediatric liver transplants were performed at Organ Transplantation Center, Sisli Memorial Hospital, Istanbul, Turkey, between August 2006 and November 2012. Of these, the first 100 consecutive pediatric liver transplant patients were retrospectively analyzed.
One hundred three liver transplants were performed in 100 children (mean age, 4.7 y; age range, 4.4 mo to 17.3 y; 53% female, 47% male; mean body weight, 17.2 kg; range, 4.5 to 75 kg). Biliary atresia (27%) and progressive familial intrahepatic cholestasis (18%) were the most common causes of liver disease. Of all the cases, 88.4% were living-donor liver transplants. Arterial reconstruction was performed under an operating microscope in most cases. Duct-to-duct biliary anastomoses were preferred in anatomically favorable cases. Mean hospital stay was 17.5 days. Median follow-up was 19.9 months (range, 6 to 66.1 mo). The main complication after surgery was infection (34%). Postoperative technical complications included hepatic arterial thrombosis (3.9%), portal venous thrombosis (6.8%), and biliary leak (6.8%). One-, 3-, and 5-year patient survivals were 89.8%, 89.8%, and 83.8%. There were no serious postoperative complications in the living donors.
Living-donor liver transplant in pediatric patients is a safe alternative to deceaseddonor transplant. It is becoming the most frequent treatment option for end-stage liver disease in pediatric patients in our center, given the paucity of pediatric deceased-donor organs.
There has been considerable recent progress liver transplantation (LTX). The postreperfusion syndrome has clearly defined and typically responds to vasopressin and/or methylene blue when refractory to catecholamine therapy. Diastolic dysfunction and cirrhotic cardiomyopathy are prevalent and important in LTX recipients. The high cardiovascular risk and the increasing medical complexity of the current liver transplant recipient have stimulated the publication of guidelines for cardiovascular assessment before LTX. Cardiac surgery is increasingly more successful in patients with cirrhosis, including simultaneous heart-liver transplantation. Cardiopulmonary bypass in LTX is indicated for hemodynamic rescue and, at some centers, serves as the hemodynamic platform for liver implantation. Although acute renal injury is common after LTX, early diagnosis is now possible with novel biomarkers. Earlier detection of postoperative renal dysfunction may prompt intervention for renal rescue. The metabolic milieu in LTX remains critical. Regular insulin therapy may be more effective than infrequent large bolus therapy for potassium homeostasis. Careful titration of insulin therapy may improve freedom from severe hyperglycemia to decrease morbidity. Since the organization of dedicated anesthesia care teams for LTX improves perioperative outcome, this aspect of perioperative care is receiving systematic attention to optimize safety and quality. The specialty of LTX is likely to continue to flourish even more, given these pervasive advances.
Background:
Oral health and dental maintenance have become part of the standard of care for pediatric liver transplant recipients. These individuals tend to suffer particularly from dental problems, such as gingival enlargement, gingivitis, poor oral hygiene, dental hypoplasia, and caries. Saliva composition influences oral hygiene and disease states. We investigated saliva composition and its association with the oral health of young recipients of liver transplants.
Methods:
In 70 patients, 36 liver transplant recipients (ages 2-23 years) and 34 healthy controls (ages 4-21 years), we measured the following variables: (a) oral hygiene, (b) gingival inflammation, (c) caries status, (d) dental calculus formation, (e) oral mucosal pH, and (f) salivary protein composition.
Results:
Lower mean decayed, missing, and filled teeth index (P=0.0038), higher mean gingival index (P=0.0001), and higher mean calculus score (P=0.003) were found in the transplanted study group compared with the control. The mean mucosal pH for seven intraoral sites was higher in the transplant group (P=0.0006). The median salivary albumin concentration was significantly lower in the transplant group (P=0.01), as was the median salivary albumin/total protein ratio (P=0.0002).
Conclusions:
In post-liver transplant pediatric recipients, low incidence of caries, together with high incidence of dental calculus, could be attributed to elevated oral mucosal pH. Salivary albumin and immunoglobulin A levels were relatively low in these patients. Clinicians should pay particular attention to the oral health and dental care of liver transplanted children.
The idea of donating part of the liver from a living donor was conceived and described in the late 1960s, but it took more than 20 years to implement clinically. In December 1988, Raia and colleagues attempted the first living donor liver transplantation (LDLT) on a 4-year-old boy who died 6 days after the transplant. In July 1989, the first successful LDLT was performed by Russell Strong in Australia; a pediatric patient received a left lateral segment (segments II and III) from his mother. This was followed by the first successful LDLT of a child in the United States by Cristoph Broelsch at the University of Chicago; their team performed 20 cases in the ensuing 12 months.
Sixteen recipients of neonatal liver grafts were compared with 114 contemporaneous pediatric recipients of grafts from older donors. Graft and patient survival were worse in the neonatal group although the differences were not statistically significant. Patients with neonatal livers who had no technical complications required a longer time postoperatively to correct jaundice and a prolonged prothrombin time. These functional differences were limited to the 1st postoperative month and the end result was the same as with liver transplantation from older donors.
Purpose: To evaluate the effectiveness of endovascular management of steno-oclusive disease in liver transplants. Methods: Retrospective review of liver transplant recipients with hepatic artery stenosis (HAS) or thrombosis (HAT) was performed. The HAS group was treated with balloon angioplasty with selective stent placement. The HAT group was treated with catheter-directed thrombolysis. Primary, unassisted, and assisted patency and graft survival rates were calculated. Results: In all, 31 patients were identified (21 males; mean age, 51 years). A total of 25 of 31 (81%) patients had HAS and 6 of 31 (19%) had HAT. Collectively, a total of 35 endovascular procedures were performed to treat HAS in 25 patients. Overall technical success rate was 91%, with 11% major complication rate. Primary-assisted patency rate and graft survival at 6 and 12 months were 87% and 81%, and 76% and 72%, respectively. Only 1 successful thrombolysis of HAT was achieved. Conclusion: Endovascular management is effective for HAS but not for HAT.
To clarify inconsistencies in the literature we performed a systematic review to identify the incidence, risk factors and outcome of early hepatic artery thrombosis (eHAT) after liver transplantation. We searched studies identified from databases (MEDLINE, EMBASE, Science Citation Index) and references of identified studies. Seventy-one studies out of 999 screened abstracts were eligible for this systematic review. The incidence of eHAT was 4.4% (843/21, 822); in children 8.3% and 2.9% in adults (p < 0.001). Doppler ultrasound screening (DUS) protocols varied from 'no routine' to 'three times a day.' The median time to detection was at day seven. The overall retransplantation rate was 53.1% and was higher in children (61.9%) than in adults (50%, p < 0.03). The overall mortality rate of patients with eHAT was 33.3% (range: 0-80%). Mortality in adults (34.3%) was higher than in children (25%, p < 0.03). The reported risk factors for eHAT were, cytomegalovirus mismatch (seropositive donor liver in seronegative recipient), retransplantation, arterial conduits, prolonged operation time, low recipient weight, variant arterial anatomy, and low volume transplantation centers. eHAT is associated with significant graft loss and mortality. Uniform definitions of eHAT and uniform treatment modalities are obligatory to confirm these results and to obtain a better understanding of this disastrous complication.
In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation.
We report a multicenter, prospective, randomized, open-label trial investigating the effect of lower levels and delayed introduction of tacrolimus on renal function in liver transplant recipients. Adult patients with good renal function undergoing primary liver transplant were randomized to either: group A (standard-dose tacrolimus [target trough levels >10 ng/mL] and corticosteroids; n = 183); group B (mycophenolate mofetil [MMF] 2g/day, reduced-dose tacrolimus [target trough levels </=8 ng/mL], and corticosteroids; n = 170); group C (daclizumab induction, MMF, reduced-dose tacrolimus delayed until the fifth day posttransplant and corticosteroids, n = 172). The primary endpoint was change from baseline in estimated glomerular filtration rate (eGFR) at 52 weeks. The eGFR decreased by 23.61, 21.22 and 13.63 mL/min in groups A, B and C, respectively (A vs C, p = 0.012; A vs B, p = 0.199). Renal dialysis was required less frequently in group C versus group A (4.2% vs. 9.9%; p = 0.037). Biopsy-proven acute rejection rates were 27.6%, 29.2% and 19.0%, respectively. Patient and graft survival was similar. In conclusion, daclizumab induction, MMF, corticosteroids and delayed reduced-dose tacrolimus was associated with less nephrotoxicity than therapy with standard-dose tacrolimus and corticosteroids without compromising efficacy or tolerability.
To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction, 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 +/- 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients.
Pediatric liver transplantation with reduced size donor organs (RLT) has evolved into a standard clinical procedure increasing the choices of recipients for their treatment. Nevertheless organ availability remains a major problem. The authors therefore have proposed to study the use of hepatic segments from living related donors (LRT) in a group of 20 children less than 2 years of age or weighing less than 15 kg, in whom standard indications for transplantation existed. Volunteer related donors were selected after medical and psychiatric evaluations, and the suitability of the donor's liver was established by functional and radiologic criteria. A two-stage informed consent process assured appropriate "volunteerism." Nineteen infants received LRT as first grafts and one as a second graft. Seventeen of the recipients are alive 3 to 18 months after LRT. Fifteen of 20 patients are currently at home with the original graft and normal liver function (bilirubin less than 1.5 mg/dl) after a median hospital stay of 27 days (range, 14-93 days). Four patients underwent retransplantation, in all cases due to arterial thrombosis. The overall graft survival for 20 primary LRTs is 75%, with follow-up between 3 and 18 months. A number of technical problems occurred during our initial trial, the most aggravating being vascular thrombosis. Refined approaches to vascular reconstruction should reduce the incidence of thrombosis and improve the rate of survival in future cases. The donor group for the initial 20 LRT procedures comprised 12 mothers, 7 fathers, and 1 grandmother. In addition one father and one uncle, who was an identical twin of the recipient's father, who did not qualify for anatomic reasons, were used in repeat LRT. All donors survived and are now in normal health between 3 and 18 months after LRT, having returned to all activities enjoyed before donation. The median hospital stay was 6 days (range, 5-14). Complications were minimal, and all were limited to the first three procedures, in which a full left hepatectomy was performed. After alteration of the procedure into a left lateral segmentectomy, no complications were encountered. The left lateral segmentectomy presents minimal surgical trauma to the liver and should remain the primary approach for obtaining a liver graft from a living donor. For children, transplantation of a left lateral segment from a live donor provides a new way of providing a transplant of appropriate size and with good function. The success of this program has led to the acceptance of LRT for general clinical application in the authors' institution.
OBJECTIVE: The authors evaluate the safety, applicability, and effectiveness of a new technique for split-liver transplantation. SUMMARY BACKGROUND DATA: Split-liver transplantation offers an attractive way to increase the donor pool for cadaveric liver transplantation. The application of this concept has been hampered by inferior patient and graft survivals and higher complication rates. Without supportive data, the concern about increasing biliary leakage and poor initial graft function persisted. The authors focused on the causes of these complications by presenting a new technique to eliminate these problems. METHODS: Liver splitting was performed in the heart-beating cadaveric organ donor, using the technique described for procurement of the left lateral lobe of a live donor. A detailed description of the technique is presented. A retrospective review of the first 14 transplantations resulting from 7 in situ splitting procedures was collected. The results were compared with 19 conventional split-live
The book describes in detail the technical aspects of Living Donor Liver Transplantation (LDLT), the routine practice of the world renowned Liver Transplant Team at Hong Kong’s Queen Mary Hospital, and our views on various issues of the operation. The thorough review on the history and technical procedures of LDLT and discussion on various aspects of the operation and its future perspectives will serve as a unique reference for surgeons, researchers, nurses, medical students, patients and laypersons seeking information on LDLT. This latest edition offers updated operative results from our center and the latest modifications of the technique. With contributions from a leading microvascular surgeon, a critical care clinician, a psychiatrist, and two anesthetists from the same liver transplant team, the LDLT experience at Queen Mary Hospital is depicted in an even greater extent. © 2011 by World Scientific Publishing Co. Pte. Ltd. All rights reserved.
Pediatric liver transplantation with reduced size donor organs (RLT) has evolved into a standard clinical procedure increasing the choices of recipients for their treatment. Nevertheless organ availability remains a major problem. The authors therefore have proposed to study the use of hepatic segments from living related donors (LRT) in a group of 20 children less than 2 years of age or weighing less than 15 kg, in whom standard indications for transplantation existed. Volunteer related donors were selected after medical and psychiatric evaluations, and the suitability of the donor's liver was established by functional and radiologic criteria. A two-stage informed consent process assured appropriate "volunteerism." Nineteen infants received LRT as first grafts and one as a second graft. Seventeen of the recipients are alive 3 to 18 months after LRT. Fifteen of 20 patients are currently at home with the original graft and normal liver function (bilirubin < 1.5 mg/dl) after a median hospital stay of 27 days (range, 14-93 days). Four patients underwent retransplantation, in all cases due to arterial thrombosis. The overall graft survival for 20 primary LRTs is 75%, with follow-up between 3 and 18 months. A number of technical problems occurred during our initial trial, the most aggravating being vascular thrombosis. Refined approaches to vascular reconstruction should reduce the incidence of thrombosis and improve the rate of survival in future cases. The donor group for the initial 20 LRT procedures comprised 12 mothers, 7 fathers, and 1 grandmother. In addition one father and one uncle, who was an identical twin of the recipient's father, who did not qualify for anatomic reasons, were used in repeat LRT. AH donors survived and are now in normal health between 3 and 18 months after LRT, having returned to all activities enjoyed before donation. The median hospital stay was 6 days (range, 5-14). Complications were minimal, and all were limited to the first three procedures, in which a full left hepatectomy was performed. After alteration of the procedure into a left lateral segmentectomy, no complications were encountered. The left lateral segmentectomy presents minimal surgical trauma to the liver and should remain the primary approach for obtaining a liver graft from a living donor. For children, transplantation of a left lateral segment from a live donor provides a new way of providing a transplant of appropriate size and with good function. The success of this program has led to the acceptance of LRT for general clinical application in the authors' institution.
A pediatric end-stage liver disease (PELD) score for children with chronic liver disease using easily obtainable, objective, verifiable parameters, would be useful to prioritize children awaiting liver transplantation.
Data from the Studies of Pediatric Liver Transplantation (SPLIT), a consortium of 29 U.S. and Canadian centers, were used to develop the PELD score. Two pretransplantation endpoints were evaluated: (1) death, n=884; and (2) death or moving to the intensive care unit (ICU), n=779. The analyses were restricted to children with chronic liver disease who were listed for a first transplant. Preliminary analyses of 17 possible factors yielded 6 parameters of interest: age <1 year, total bilirubin, international normalized ratio (INR), albumin, growth failure (height or weight Z score <-2), and calculated glomerular filtration rate. In a univariate Cox regression analysis, age, bilirubin, INR, and albumin were significant (P<0.01) predictors of both endpoints; glomerular filtration rate was not significant for either endpoint; and growth failure was significant for death/ICU but not death alone. In the multivariate analyses, age, bilirubin, and INR were significant for the death endpoint; and bilirubin, INR, growth failure, and albumin were significant for the death/ICU endpoint. From these results, three PELD models were evaluated to predict both outcomes at 3 and 6 months: PELD 1 (age, bilirubin, INR); PELD 2 (bilirubin, INR, albumin, growth failure); and PELD 3 (bilirubin, INR, albumin, growth failure, and age). The area under the receiver operating characteristic curve (AUC ROC) was used to compare models. For PELD 3, the most inclusive model, the AUC ROC at 3 months was 0.92 for death and 0.82 for "death-moved to ICU." A comparison of the AUC ROCs for the other models and for the model of end-stage liver disease ([MELD], the adult end-stage liver disease severity score model), none of which performed better than PELD 3, are presented.
A model using five objective parameters can accurately predict death or death-moved to ICU in children awaiting liver transplantation.
The aim of this study was to determine the outcome of venous conduits used in living donor liver transplantation (LDLT). We analyzed the portal vein complications in 66 LDLT recipients and 48 cadaveric reduced-size liver transplant (RLT) recipients performed from November 1989 through January 1995. Three different venous conduits were utilized in the LDLT recipients: Group 1, reconstructed vein from the living donor, n=18; Group 2, cadaveric cryopreserved iliac vein, n=37; and Group 3, cadaveric cryopreserved femoral vein, n=11. Overall, 47 percent of the patients were less than one year of age; the age distribution was not significantly different among the groups. The incidence of early thrombosis was significantly greater in LDLT Group 1,(33%) than any of the other groups (LDLT Group 2, 8%; LDLT Group 3, 9%; and RLT, 4%; P<0.005 vs. reduced graft and < 0.03 vs. other LDLT groups). The incidence of late portal vein stenosis or thrombosis was significantly higher in the LDLT Group 2, (51%) than any of the other groups (LDLT Group 1, 16%; LDLT Group 3, 9%; RLT 4%;P<0.005 vs. cadaveric and < 0.02 vs. LDLT Group 1 and LDLT Group 3). Five year actuarial graft and patient survival for patients who have experienced portal vein thrombosis or stenosis is 61% and 67%, respectively, versus 67% and 71% for those patients who have not experienced portal vein pathology, P=ns. Based on this experience, we recommend avoiding the use of cryopreserved iliac vein for portal vein reconstruction in liver transplantation. Every effort should be taken to eliminate the need for venous conduits in liver transplantation. If venous conduits must be utilized, cryopreserved femoral veins seem to provide superior patency rates. Careful clinical and ultrasonographic monitoring of patients at high risk for late venous thrombosis permits therapy with excellent graft and patient survival.
Ein Spenderleberorgan wurde so getrennt, da der linke Teil (Segment II und III ohne Vena cava) auf ein Kind, der rechte Teil (Segment 1, IV, V bis VIII) auf einen Erwachsenen erfolgreich transplantiert werden konnte. Choledochus und Arteria hepatica communis bzw. propria blieben beim linken Leberteil, Vena portae beim rechten. Beim Empfnger der linken Seite blieb die eigene Vena cava erhalten; in sie wurde die linke Vena hepatica anastomosiert; die brigen Anastomosen wurden in blicher Weise durchgefhrt. Beim Empfnger des rechten Leberteiles wurde die spenderseitige Arteria hepatica dextra mit einem Saphenainterponat verlngert und mit der Arteria hepatica communis des Empfngers anastomosiert; zwei getrennte Hepaticusste wurden mit einer Jejunumschlinge anastomosiert. Die brigen Anastomosen wurden in typischer Weise ausgefhrt. Die Mglichkeit der Verwendung einer Spenderleber fr zwei Empfnger (Splitting-Transplantation) ist damit gezeigt.A donor liver was divided in such a way that the left part (segment 11 and III without caval vein) could be transplanted into a child, the right part (segment I, IV, V to VIII) into an adult successfully. Common bile duct and common hepatic artery remained with the left part of the liver, portal vein with the right one. In the recipient of the left part of the liver the own caval vein was preserved and anastomosed with the left hepatic vein; the other anastomoses were carried out in the typical way. In the recipient of the right part of the liver the right hepatic artery of the graft was anastomosed with the recipient's common hepatic artery using a saphenous interponate. Two separate intrahepatic bile ducts were anastomosed with a Roux-en-Y loop of the jejunum. The other anastomoses were carried out in the typical way. Thus the possibility of using one donor liver for two recipients (splitting transplantation) has been demonstrated.
To examine the outcome of biliary atresia (BA) and to identify prognostic factors using a national database.
All children born between January 1987 and December 2008 who underwent the Kasai surgical procedure for BA were retrieved from the Netherlands Study Group on Biliary Atresia Registry database. Outcomes were measured in terms of clearance of jaundice (bilirubin <1.17 g/dL, or 20 μmol/L, within 6 months after surgery) and 4-year transplant-free survival. Two cohorts, one from 1987-1997 and the other from 1998-2008, were compared. Survival rates were determined using Kaplan-Meier analysis, and prognostic factors were tested with univariate and multivariate analyses.
Between January 1987 and December 2008, 214 patients underwent Kasai surgery for BA. In this series, the 4-year transplant-free survival was 46%±4%, and 4-year overall survival was 73%±3%. Clearance of jaundice, surgery within 60 days, and postoperative antibiotic prophylaxis use were independently associated with increased transplant-free survival. The yearly caseload per center (range, 0.5-2.1) was not correlated with transplant-free survival (r=0.024; P=.73).
During the past 2 decades, outcome parameters have remained constant and are comparable with those reported from other Western countries, despite a relatively low annual caseload per center. Timely surgical correction and postoperative antibiotic therapy were associated with a higher transplant-free survival rate.
Early hepatic artery thrombosis remains one of the major causes of graft failure and mortality in liver transplant recipients. It is the most frequent severe vascular complication after orthotopic liver transplantation (OLT) accounting for >50% of all arterial complications. Most patients need to be considered for urgent liver retransplantation.
Among 911 OLTs in 862 from 1989 to 2011, we observed 23 cases (2.6%) of acute early hepatic artery thrombosis. Seventeen patients were qualified immediately for liver retransplantation, and 6 underwent endovascular therapies, including intra-arterial heparin infusion or percutaneous transluminal angioplasty with stent placement.
Among patients who were assigned to early liver retransplantation, 11/17 survived with 3 succumbling due to postoperative complications, including 1 portal vein thrombosis, and 3 succumbling on the waiting list. All patients who underwent endovascular therapy survived with an excellent result obtained in 1 who underwent treatment<24 hours after arterial thrombosis. In 2 patients we achieved a satisfactory result not requiring retransplantation, but 3 patients assigned to endovascular treatment>24 hours after arterial thrombosis needed to be reassigned to liver retransplantation because of poor results of endovascular treatment.
Endovascular treatment efforts should be made to rescue liver grafts through urgent revascularization depending on the patient's condition and the interventional expertise at the transplant center, reserving the option of retransplantation for graft failure or severe dysfunction.
1. Histological abnormalities are commonly present in late posttransplant biopsies from pediatric liver allograft recipients. 2. Many of the changes are seen in children who appear to be clinically well with good graft function. 3. In comparison with adults, children may be more prone to developing late rejection (possibly related to noncompliance with immunosuppression) and biliary/vascular complications, but they are much less likely to suffer problems with disease recurrence. 4. De novo autoimmune hepatitis occurs in 5% to 10% of children after transplantation and may represent a hepatitic form of late cellular rejection. Most cases respond to treatment with increased immunosuppression. 5. Recent studies have shown a high frequency of unexplained (idiopathic) chronic hepatitis in late posttransplant biopsies from children. This is associated with the development of graft fibrosis and cirrhosis. 6. Further studies are required to investigate the role of protocol liver biopsies in determining therapeutic strategies in children who appear to have good graft function according to noninvasive investigations.
Liver transplantation (OLT) has become the only treatment modality for patients with end-stage liver diseases. Establishment of standard liver transplantation technique, development of better immunosuppressive medications and accumulated experience using them safely, and improvement of intensive care and anesthesia played major role to have current 88%–90% 1-year survival after liver transplantation. As liver transplantations became more successful with the growing experience and development in the field, the increased demand for liver allografts could not match the available supply of donor organs. As a result of this imbalance, each year nearly 3000 patients die in the United States awaiting liver transplantation on the national waiting list. Split liver transplantation (SLT) has been perceived as an important strategy to increase the supply of liver grafts by creating 2 transplants from 1 allograft. The bipartition of a whole liver also carries utmost importance by increasing the available grafts for the pediatric patients, where size-matched whole liver allografts are scarce, leading increased incidence of waiting list mortality in this group.
Early hepatic arterial thrombosis after living-donor liver transplantation is a cause of graft loss and patient mortality. We analyzed early hepatic arterial thrombosis after pediatric living-donor liver transplantation.
Since September 2001, we performed 122 living-donor liver transplants on 119 children. Ten hepatic arterial thromboses developed in the early postoperative period. The 7 male and 4 female patients of overall mean age of 6.3±6.1 years underwent 5 left lateral segment, 3 right lobe, and 2 left lobe transplantations.
Among 10 children with hepatic arterial thrombosis, 8 diagnoses were made before any elevation of liver function tests. One child displayed fever at the time of the hepatic arterial thrombosis. The median time for diagnosis was 5 days. Hepatic arterial thrombosis was treated with interventional radiologic techniques in 9 children, with 1 undergoing surgical exploration owing to failed radiologic approaches, and a reanastomosis using a polytetrafluoroethylene graft. Successful revascularization was achieved in all children, except 1. Four children died, the remaining 6 are alive with good graft function. During the mean follow-up of 52.7±18.8 months, multiple intrahepatic biliary stenoses were identified in 1 child.
Routine Doppler ultrasonography is effective for the early diagnosis of hepatic arterial thrombosis. Interventional radiologic approaches such as arterial thrombolysis and intraluminal stent placement should be the first therapeutic choices for patients with early hepatic arterial thrombosis; if radiologic methods fail, one must consider surgical exploration or retransplantation.
Pediatric liver transplant recipients represent an important target population for primary care health professionals as well as transplant practitioners. With improving patient and graft survival, new concerns now face health care professionals caring for the transplant community, namely the long-term complications of immunosuppressive therapy and the potential for withdrawal of immunosuppression, transplant recipients' quality of life, and the persistent shortage of donor organs leading to morbidity and mortality on the waiting list. These issues require constant collaboration between pediatricians, transplant hepatologists, transplant surgeons, nurses, dieticians, social workers, psychologists, and other supporting services.
Heffron TG, Pillen T, Smallwood G, Henry S, Sekar S, Casper K, Solis D, Tang W, Fasola C, Romero R. Incidence, impact, and treatment of portal and hepatic venous complications following pediatric liver transplantation: A single-center 12 year experience. Pediatr Transplantation 2010: 14:722–729. © 2010 John Wiley & Sons A/S.
Abstract: PVT or PVS and HVOO are known causes of graft and patient loss after pediatric liver transplantation. Increased incidences of these complications have been reported in partial livers including DDSLT or LDLT. From 1997 to 2008, 241 consecutive pediatric patients received 271 hepatic grafts at a single center. Median follow-up is 1856 days. Surgical technique, demographics, lab values, and radiologic imaging procedures were obtained utilizing OTTR® to evaluate the relationship of portal and hepatic complications with risk factors, patient and graft survival. Grafts were composed of 115/271 (42.4%) partial livers of which 90 (33.2%) were DDSLT and 25 (9.2%) LDLT. Of 271 patients, 156 (57.6%) received whole-sized grafts. There were six PVC in five patients with one patient requiring retransplantation (0.34%) and no patient deaths. Utilizing all three hepatic vein orifices on the recipient hepatic vena cava and the donor hepatic vein cut short enables a wide hepatic outflow tract unlikely to twist. None of the 241 patients developed early or late complications of the hepatic vein. None of the last 128 consecutive patients who received 144 grafts over seven and a half yr have developed either early or late complications of the hepatic or portal vein. Partial-graft actuarial survival was similar to whole-graft survival (87.2% vs. 85.3% at one yr; 76.6% vs. 80.2 at three yr; p = 0.488). Likewise, patient survival was similar between partial grafts and whole grafts (93.8% vs. 93.1% at one yr; 89.8% vs. 87.2% at three yr; p = 0.688) with median follow-up of 1822 (±1334) days. Patients receiving partial livers were significantly younger and smaller than patients receiving whole livers (p < 0.001). Portal and hepatic venous complications may have negative effects on patient or graft survival after pediatric liver transplantation. In our series, there was one graft and no patient loss related to portal or hepatic venous complications after pediatric liver transplantation over 12 yr.
Hepatic artery thrombosis (HAT) is the most frequent vascular complication following orthotopic liver transplantation. Urgent retransplantation has been considered as the mainstay therapy. Surgical revascularization is an effective alternative in asymptomatic patients. Endovascular therapies including intra-arterial thrombolysis, percutaneous transluminal angioplasty (PTA), and stent placement have shown encouraging results in recent years; however, their use remains controversial because of potential risk of hemorrhage. Until June 2009, 69 cases were published in 16 reports describing therapeutic potential of endovascular modalities. Interventions were performed as early as within 4 h to as late as 120 days in patients ranging from 4 months to 64 years of age. Majority of published reports suggested the use of urokinase. Thrombolysis was successful in 47 out of 69 (68%) patients. Bleeding was the most common complication including fatal intra-abdominal hemorrhage in three patients. Twenty-nine out of 47 (62%) patients underwent further intervention in the form of PTA, stenting, or both. The follow-up patency ranged from 1 month to 26 months. In conclusion, whenever possible, efforts should be made to rescue the liver grafts through urgent revascularization (surgical and/or endovascular) depending on patient's condition and interventional expertise at the transplant center; reserving the option of retransplantation for failure, complications, and cases with severe clinical symptoms or allograft dysfunction.
Biliary atresia is a rare, serious and challenging disease in newborn children. Its aetiology remains unknown. Optimal management at specialist centres with resultant better overall outcomes is achieved through a multidisciplinary team approach. The Kasai portoenterostomy performed early in life remains the only surgical repair procedure. Two thirds of patients will clear their jaundice after a Kasai procedure, but only about one third will retain their livers after the first decade of life. Failure of this procedure leaves liver transplantation as the only chance for survival, and this disease is the commonest indication for liver transplantation in children. With modern medical care and refinements in surgical techniques, survival after either or both of these procedures is about 90%. Early referral to specialist centres and long-term specialist care remains the key to successful treatment of this condition.
Objective:
To determine the factors that influence patient survival after in vivo split liver transplantation (SLT).
Summary background data:
Split liver transplantation is effective in expanding the donor pool, and its use reduces the number of deaths in patients awaiting orthotopic liver transplantation. Early SLTs were associated with poor outcomes, and acceptance of the technique has been slow. A better understanding of the factors that influence patient and graft survival would be useful in widening the application of SLT.
Methods:
During a 3.5-year period, 55 right and 55 left lateral in vivo split grafts were transplanted in 102 pediatric and adult recipients. The authors' in vivo split technique has been previously described. Median follow-up was 14.5 months. Recipient, donor, and surgical variables were analyzed for their effect on patient survival after SLT.
Results:
Overall survival rates of patients who received an SLT were not significantly different from those of patients who received whole organ transplants. Survival of left lateral segment recipients, at median follow-up time, was 76% versus 80% in patients receiving a trisegment. Fifty of 102 patients (49%) were high-risk urgent recipients (United Network for Organ Sharing [UNOS] status 1 and 2A) and 52 (51%) were nonurgent recipients (UNOS status 2B, 3). High-risk recipients had a survival rate significantly lower than that of nonurgent recipients. By univariate comparison, two variables-UNOS status and number of transplants per patient-were significantly associated with an increased risk of death. Preoperative recipient mechanical ventilation, preoperative prothrombin time, donor sodium level, donor length of hospital stay, and warm ischemia time approached significance. The type of graft (right vs. left) did not reduce the survival rate after transplantation. Multivariate logistic regression analysis identified UNOS status and length of donor hospital stay as independent predictors of survival.
Conclusions:
Patient survival of in vivo SLT is not significantly different from that of whole-organ orthotopic liver transplantation. The variables affecting outcome of in vivo SLT are similar to those in whole-organ transplantation. in vivo SLT should be widely applied to expand a severely depleted donor pool.
Early experience with living donor liver transplantation (LDLT) was often complicated by hepatic artery thrombosis (HAT), a devastating complication resulting in graft loss. Attempting to reduce the incidence of HAT, we undertook a retrospective review of all children at our institution undergoing LDLT between March 2000 and August 2007, with the hepatic artery anastomosis performed by a single microvascular surgeon. Transplant surgeons performed the remainder of the operation. Patient outcomes were evaluated, including 1-year arterial and biliary complications, as well as overall survival. End-to-end hepatic arterial anastomoses were performed in 35 patients (median age: 15 months). Median posttransplant follow-up was 39 months (range: 0 to 90 months). One patient with a diffuse coagulopathy was retransplanted for HAT; this patient also demonstrated portal and hepatic vein thromboses. Biliary complications occurred in seven patients: three leaks, one cholangitis, one nonspecific dilatation, and two strictures. The median posttransplant follow-up was 39 months (range: 0 to 90 months). One- and 5-year patient survival was 94% and 94%, respectively. Very low rates of HAT can be achieved with LDLT using microsurgical techniques for hepatic arterial anastomoses. Outstanding long-term liver graft function can be achieved after LDLT when plastic surgeons and transplant surgeons collaborate together to reduce technical complications.
The use of CNI in pediatric LTx has dramatically improved the outcome for children with end-stage liver disease by significantly reducing the rate of acute and chronic rejection. Long-term concerns about CNI-induced nephrotoxicity and other adverse effects remain an issue, particularly as the emphasis moves from short-term survival to long-term quality of life. This review summarizes lessons learnt from pediatric and adult solid organ transplantation in minimizing CNI use in immunosuppression protocols in children following LTx. There are three models for CNI minimization: dose reduction, withdrawal or avoidance, supplemented by the use of IL-2 receptor blocking antibodies in the peri-transplant period, and early transition to alternate drugs such as MMF or SRL. Prospective studies evaluating reduction or withdrawal protocols in adult and pediatric LTx indicate that rejection rates are comparable with traditional CNI-based immunosuppression and that two and five yr patient and graft survival are similar, with recovery in renal function. There are few studies evaluating complete avoidance of CNI, apart from that in renal transplantation, although the benefits of long-term reduction in cardiovascular, metabolic, and possibly neoplastic side effects may justify this approach. It is not clear yet how CNI minimization will affect the development of tolerance but experimental and preliminary clinical studies indicate that CNI and steroid avoidance or minimization in the peri-operative period may favor the development of long-term graft tolerance. In summary, CNI minimization may be safe and effective in the short term but large-scale pediatric randomized studies are required to evaluate the long-term efficacy of these regimes in the development of chronic rejection, PTLD, and graft tolerance.
To analyze the risk factors in the development of hepatic artery thrombosis (HAT) and assess the impact of our perioperative management for HAT on the long-term outcome after pediatric living donor liver transplantation (LDLT), we reviewed 382 patients under 12 yr of age who underwent 403 LDLT from January 1996 to December 2005. One- and 10-yr patient survival rates were 78% and 78% in the patients with HAT (27 patients; 6.7%), and 84% and 76% in the patients without HAT, respectively (p = n.s.). Univariate analysis showed gender (female), body weight (lower), and graft-to-recipient weight ratio (higher) were significant risk factors in the patients with HAT (p < 0.05). Patients with Doppler ultrasound signal loss of the hepatic artery (HA) accompanied by an increase of liver enzymes underwent thrombectomy and reanastomosis (S-group, n = 13), and patients with a weak HA signal underwent anticoagulant therapy (M-group, n = 13). One patient underwent re-LDLT. One- and five-yr patient survival rates were 83% and 83% in the S-group, and 77% and 77% in the M-group (p = n.s.). The incidence of biliary complications in the S-group (58%) was significantly higher than that of the M-group (15%). For a successful long-term outcome, the early detection of HAT and prompt medical and surgical intervention are crucial to minimize the insult of HAT.
Unlabelled:
Previously we reported the presence of portal fibrosis in 31% (n = 84) of the grafts in protocol biopsies 1 year after pediatric liver transplantation (LTx). To assess the natural history of graft fibrosis after pediatric liver transplantation, we extended the analysis of graft histology in follow-up protocol biopsy specimens obtained 5 and 10 years after transplantation. We correlated histological results with clinical parameters at the time of LTx and during follow-up, to allow identification of risk factors for the development of fibrosis. From 1 year to 5 years after LTx, the prevalence of fibrosis increased from 31% to 65% (n = 66) but remained stable thereafter (at 10 years, 69%, n = 55). At 10 years after LTx, however, the percentage of patients with severe fibrosis had increased from 10% (at 5 years) to 29%. Of the 69% of children without fibrosis at 1 year post-transplantation, 64% (n = 39) had developed some degree of fibrosis at 10 years. Fibrosis was strongly related to transplant-related factors such as prolonged cold ischemia time, young age at the time of transplantation, high donor/recipient age ratio, and the use of partial grafts (P < 0.05). Fibrosis was not significantly related to rejection, chronic hepatitis, or the nature of the immunosuppressive therapy.
Conclusion:
Biopsies after pediatric LTx show that most grafts developed fibrosis within 5 years. At 10 years after LTx, the graft fibrosis had progressed to severe fibrosis in at least 25% of the patients. Development of fibrosis, starting either before or after the first year post-LTx, was strongly related to transplant-related factors, indicating the importance of these factors to long-term graft prognosis.
The factors that influence the long-term histological outcome of transplanted liver allografts in children are not yet fully understood, and the role of surveillance biopsies in patients with normal graft function remains controversial. The aims of this study were to describe the long-term graft histology of pediatric liver transplant recipients surviving at least 3 years and to analyze factors correlating with long-term histological outcome. Histological slides of 63 long-term liver transplant recipients were assessed for inflammation and fibrosis. The histological findings were correlated with clinical, biochemical, serological, and radiological findings. A significant proportion of biopsies from these patients showed some type of histological abnormalities, with fibrosis being observed in 61 (97%) patients. Duration of transplantation of >6 years and > or =grade 2 inflammation were significantly associated with advanced fibrosis. We could not identify any correlation between > or =stage 3 fibrosis and donor age, cold and warm ischemia time, history of de novo autoimmune hepatitis, hepatic artery thrombosis, chronic rejection, or alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase values. In conclusion, liver fibrosis appears to be a common finding in long-term pediatric liver transplant survivors. The cause of this fibrosis is uncertain, and normal alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels do not exclude the presence of significant fibrosis.
Portal vein thrombosis (PVT) after liver transplantation is a fatal complication. The risk factors for PVT after LDLT remain to be clarified.
A total of 287 consecutive living donor liver transplantations have been performed. Some clinical parameters of the recipients with and without postoperative PVT were compared to analyze the risk factors for PVT.
A total of 20 recipients (7%) were complicated with PVT. Of these 20, 6 patients had late onset PVT (> or =3 months after LDLT). There were no significant risk factors for early onset PVT (<3 months after LDLT). In contrast, a venous conduit for interposition was a significant risk factor for late onset PVT (multivariate analysis, p=0.02).
Use of venous conduit for portal vein interposition might be limited for better results although longer term follow-up and further case accumulation are necessary for more definitive conclusions.
34 patients treated with cyclosporin A received 36 cadaveric organ allografts (32 kidneys, 2 pancreases, and 2 livers), 26 kidneys are still supporting life, 3 after more than a year; the pancreases and livers are also functioning. 20 patients are not receiving steroids, and 15 of these have not had any additional immunosuppressive agents. In these patients infectious complications have not been severe, but a gastroduodenal lymphoma has developed in 1 patient. 6 patients were given 'Cytimum' (a cyclophosphamide derivative) and steroids in addition to cyclosporin A: 5 of these died of infections and 1 also had a lymphoma. 11 patients received additional steroids: 1 of these died from septicaemia and lymphoma. Nephrotoxicity can be avoided by perioperative hydration and forced diuresis. Cyclosporin A is effective on its own and is a very potent immunosuppressive drug. Additional immunosuppressive agents may lead to severe complications.
Surgical reduction of donor livers to treat small children has been performed successfully in several centers. While this procedure improves the allocation of livers, it does not increase the organ supply. We have extended reduced-size orthotopic liver transplantation (OLT) to treat 18 patients with 9 livers, accounting for 26% of our transplants during a 10-month period and have evaluated the results. In 18 split liver OLTs, patient survival was 67% and graft survival was 50%. In comparison, for 34 patients treated with full-size OLT during the same period, patient survival was 84% (p = 0.298) and graft survival was 76% (p = 0.126). Biliary complications were significantly more frequent in split grafts, occurring in 27%, as compared to 4% in full-sized grafts (p = 0.017). Primary nonfunction (4% versus 5.5%) and arterial thrombosis (6% versus 9%) occurred with similar frequency in split and full-size OLT (p = not significant). These results demonstrated that split-liver OLT is feasible and could have a substantial impact in transplant practice. We believe that biliary complications can be prevented by technical improvements and that split-liver OLT will improve transplant therapy by making more livers available.
The University of Chicago program in pediatric liver transplantation continues actively to seek innovative surgical solutions to problems related to the management of children with end-stage liver disease. Among the most important problems facing these children is a shortage of donor organs, which results from three factors in addition to the actual supply of pediatric donors: the concentration of pediatric liver disease in the population younger than 2 years; the necessity for a graft that is small enough; and the epidemiology of accidents and other events that lead to organ donation. Transplantation using a liver lobe as a graft overcomes size disparity and shifts the available supply of organs from older donors to younger recipients. This work describes the technical aspects of recent innovations in the use of liver lobes in pediatric transplantation, simple reduced-size liver transplantation (RLT), split-liver transplantation (SLT), orthotopic auxiliary liver grafting (ALT), and transplantation using a living related donor (LRLT), and compares their results. Since November 1986 a total of 61 procedures have been performed in which a liver lobe was used as a graft: 26 RLT; 30 SLT, 25 in children and 5 in adults; 5 LRLT; and 1 ALT. Overall 62% of transplants performed in children have involved using a liver lobe as a graft. The rates of complications are somewhat higher than with whole-liver transplantation, but this may not be entirely the result of the complex procedures. Split liver transplantation is associated with the highest mortality and complication rates. Living related liver transplantation has been associated with complications in donors and recipients, but to date survival is 100%. Orthotopic auxiliary liver transplantation effectively corrected the metabolic defect in one patient with ornithine transcarbamylase deficiency. Overall the various modalities of using graft reduction have resulted in postoperative results similar to those achieved with full-size grafts, while pretransplantation mortality has been limited to less than 2%. Thus the use of grafts as liver lobes accomplishes the goal of reducing global mortality among children with end-stage liver disease, but at the cost of increased surgical complexity and more postoperative complications.
Hepatic artery thrombosis (HAT) is one of the most serious complications after orthotopic liver transplantation, and is associated with a high morbidity and mortality. This study retrospectively reviewed 66 liver transplants in children under the age of 10 years during a year-long period at a single institution. A total of 28 perioperative variables were analyzed to identify responsible factors of HAT. Of the 66 children, 18 (26%) developed HAT within 15 days after the transplant (HAT group); 29 (42%) had an uneventful postoperative course (control group). To avoid the possible influence of other complications 19 patients were excluded. Of the variables compared between the 2 study groups, three surgical factors (diameter of the hepatic artery--greater or less than 3 mm; type of arterial anastomosis--end-to-end versus the use of an iliac graft or aortic conduit; and number of times the anastomosis was redone--one versus more than one), were found to be significantly different (P less than .05) between HAT and control groups. Two medical factors also were significantly different: the use of intraoperative transfusion of fresh frozen plasma (FFP) and the administration of postoperative prophylactic anticoagulant treatment. A heparin and dextran-40 protocol appeared to be effective in preventing HAT (P less than .02). Moreover, after multivariate analysis, anticoagulation therapy was demonstrated to be the major independent variable influencing HAT. A better definition of factors responsible for the occurrence of HAT is required. This study should help in formulating effective methods to decrease the incidence of this dreaded complication after liver transplantation.
Because of its anatomy, the liver can be divided into two hemilivers suitable for use as two grafts for liver transplantation. The line of division is the main scissure, giving the right hemiliver (segments 5-8) and the left hemiliver (segments 2-4). Segment 1 (caudate lobe) has to be resected. The vessels are divided between the two grafts: the vena cava remains on the right; on the left, the left hepatic vein is sutured into the vena cava of the recipient, which is retained intact. The left graft retains only the left branch of the portal vein, the bile duct and the hepatic artery. The right graft retains the portal trunk, the common bile duct and the right branch of the hepatic artery. This procedure was used for emergency grafting of two patients with fulminant hepatitis when only one donor was available. Both recipients recovered from coma and regained normal liver function. However, both died from causes not specifically related to the operative technique, one from multiple organ failure on the 20th day and the other from diffuse cytomegalovirus infection on the 45th day.
A donor liver was divided in such a way that the left part (segment II and III without caval vein) could be transplanted into a child, the right part (segment I, IV, V to VIII) into an adult successfully. Common bile duct and common hepatic artery remained with the left part of the liver, portal vein with the right one. In the recipient of the left part of the liver the own caval vein was preserved and anastomosed with the left hepatic vein; the other anastomoses were carried out in the typical way. In the recipient of the right part of the liver the right hepatic artery of the graft was anastomosed with the recipient's common hepatic artery using a saphenous interponate. Two separate intrahepatic bile ducts were anastomosed with a Roux-en-Y loop of the jejunum. The other anastomoses were carried out in the typical way. Thus the possibility of using one donor liver for two recipients (splitting transplantation) has been demonstrated.
Liver transplantation, which once was an experimental procedure of no practical interest, has become the preferred treatment for infants and children dying of almost all non-neoplastic end-stage liver diseases. Liver replacement is being provided by many well-trained teams on all of the continents, as is evident from the program today--the first international symposium on pediatric liver transplantation. I have been honored in giving the first paper in the process of introducing the remarkable work of a gifted younger generation of physicians and surgeons.
Because of the rarity of child donors, in cases of adult donors room requirement for the liver graft is a major technical obstacle to liver transplantation in children. To overcome this difficulty in a child, the authors performed an orthotopic transplantation with an adult liver that had been reduced to the left lobe. The absence of technically-related complications suggests that this procedure might facilitate the performance of liver transplantation in children.
Up to 25% of babies with biliary atresia (BA) bear associated malformations that most often cluster in the polysplenia syndrome (PS). This article examines the impact of associated PS on the final outcome of the authors' BA patients and the necessary modifications of surgical technique during orthotopic liver transplantation (OLT) in these patients. The authors studied 88 consecutive infants with biliary atresia operated upon during the 10-year period between 1984 and 1993. Biliary drainage was provided by a Roux-en-Y hepaticojejunostomy. OLT was performed in 38. Eleven infants (12%) had three or more components of PS: malrotation (11), preduodenal portal vein (11), polysplenia (10), situs inversus (4), absent inferior vena cava (3), cardiac defects (2), and anomalous hepatic artery supply (2). Bile drainage was achieved in 7/11 infants (63% versus 48% for regular BA patients) 5 of whom (45% versus 31%) are jaundice-free with a mean follow-up of 105 months. Three patients received transplants (2 from living-related donor) and are alive and well with normal liver function after a mean follow-up of 35 months. Overall survival was 72% in the BA plus PS and 66% in the BA group (P = not significant [NS]). Results show that long-term bile drainage in these PS patients can be achieved at least as often as in other BA patients (45% versus 31%) (P = NS) and indicate that Kasai operation remains the best initial choice. When OLT becomes necessary, attention to vascular anatomy is required to determine the feasibility of reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS)
Infections are a major cause of morbidity and mortality after organ transplantation in children. Immunosuppression, surgery, and invasive devices all predispose to infection. A comprehensive pretransplantation evaluation can minimize risks and help anticipate special problems. Appropriate anti-microbial coverage during the perioperative period decreases the risk of infection. Bacteria and fungi are the major causes of infections occurring in the first month after transplantation. The site of infection during this period varies by organ transplanted: liver recipients often have intraabdominal infections, kidney recipients are predisposed to urinary tract infections and perinephric abscesses, and heart recipients often have respiratory tract or sternal wound infections. Viruses play a major role in infections occurring more than 1 month after transplantation, with cytomegalovirus the most significant agent. Other viruses of concern include herpes simplex virus, varicella-zoster virus, several common respiratory viruses, and Epstein-Barr virus with associated lymphoproliferative disorders. Tuberculosis, toxoplasmosis, and Pneumocystis pneumonia also occur later. Appropriate immunization and antimicrobial prophylaxis can help prevent infectious complications after transplantation.
The authors evaluate the safety, applicability, and effectiveness of a new technique for split-liver transplantation.
Split-liver transplantation offers an attractive way to increase the donor pool for cadaveric liver transplantation. The application of this concept has been hampered by inferior patient and graft survivals and higher complication rates. Without supportive data, the concern about increasing biliary leakage and poor initial graft function persisted. The authors focused on the causes of these complications by presenting a new technique to eliminate these problems.
Liver splitting was performed in the heart-beating cadaveric organ donor, using the technique described for procurement of the left lateral lobe of a live donor. A detailed description of the technique is presented. A retrospective review of the first 14 transplantations resulting from 7 in situ splitting procedures was collected. The results were compared with 19 conventional split-liver transplants performed during the same period.
Six-month patient and graft survivals after in situ split-liver transplantation were 92.8% and 85.7%, respectively. Biliary complications were absent. Postoperative courses were mostly uneventful and characterized by lower peak transaminase levels compared with standard techniques. Early graft function of extrahepatic organs procured simultaneously was excellent.
In situ split-liver transplantation provides superior results, related mainly to reduction of cold ischemic damage of the grafts and avoidance of biliary complications. In situ split-liver transplantation renders graft reduction alone obsolete and opens a donor pool for adults to receive right lobes safely. It allows for long-distance sharing between pediatric and adult liver transplant units because the procedure abolishes ex situ benching and prolonged ischemia time and provides two anatomically perfect grafts with hemostasis accomplished.
Malnutrition is a critical predictor of mortality and morbidity in children with biliary atresia who undergo orthotopic liver transplantation. Growth hormone (GH) enhances nitrogen retention in patients with chronic obstructive lung disease, sepsis, and in fasted adult volunteers. The goal of this study was to assess the acute response to recombinant human GH (rhGH) treatment in children with biliary atresia to determine whether GH therapy was likely to improve pretransplant nutritional status. Five children, aged 10-32 months, with biliary atresia and persistent cholestasis despite surgical attempts to reestablish bile flow, were studied. All five children had portal hypertension, conjugated hyperbilirubinemia, and decreased serum albumin concentrations. Length, weight, and growth velocity were decreased in all five children. Despite adequate energy and protein intake, fat stores were depleted in all five subjects, and somatic protein stores were diminished in all except one child. Baseline serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) were low (8.4 +/- 2 ng/ml and 0.2 +/- 0.1 mg/l respectively). In the four children who completed the study, serum IGF-I and IGFBP-3 levels did not change after treatment with rhGH (0.1 mg/kg/day) for 4 days. Our findings indicate that children with biliary atresia awaiting liver transplantation are insensitive to GH and that treatment with GH is unlikely to promote anabolism. A rationale exists for examining the effect of treatment with IGF-I, which mediates the anabolic effects of GH.
Liver transplantation with preservation of the recipient vena cava (the "piggy-back" technique) has been proposed as an alternative to the traditional method. We performed a randomized study on 39 cirrhotic patients, 20 who underwent the piggy-back technique (group 1) and 19 the traditional method using venovenous bypass (group 2) to evaluate the feasibility and true advantages of the piggy-back technique compared to the traditional method. Two patients were switched to the conventional technique due to the presence of a caudate lobe embracing the vena cava in one patient and a caval lesion in the other. Statistically significant differences between the two groups were only found for the warm ischemia time (48.5 +/- 13 min for piggy-back vs 60 +/- 12 min for the conventional method) and for renal failure (zero cases in group 1 vs four cases in group 2). We therefore believe that liver transplantation with the piggy-back technique can easily be performed in almost all cases, and that only a few, specific situations, such as a very enlarged caudate lobe, do not justify its routine use.