Nephrology Dialysis Transplantation 2007 22(Supplement 8):viii23-viii28; doi:10.1093/ndt/gfm649
© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Indications for pediatric liver transplantation. Data from the Heidelberg pediatric liver transplantation program
G. Engelmann1,
J. Schmidt2,
J. Oh1,
H. Lenhartz1,
D. Wenning,
U. Teufel,
M. W. Büchler2,
G. F. Hoffmann1 and
J. Meyburg1
1University of Heidelberg Department of Paediatrics, INF 150, D-69120 Heidelberg and 2University of Heidelberg Department of General, Visceral and Transplantation Surgery, INF110, D-69120 Heidelberg
Correspondence to: Guido Engelmann, M.D, University of Heidelberg, Department of Paediatrics, INF 150, D-69120 Heidelberg, Germany. Email: guido_engelmann{at}med.uni-heidelberg.de
 |
Abstract
|
|---|
Nowadays liver transplantation is an established treatment for
children with end-stage liver disease with very good 1- and
5-year survival. This has been achieved through constant improvement
of surgical techniques, new immunosuppressive drugs and clinical
management. Indications for liver transplantation in infants
and children include acute liver failure (ALF), chronic liver
failure with pruritus, complications of cholestasis and failure
to thrive. In young children, the most common liver disease
leading to transplantation is biliary atresia. Biliary atresia
accounts for at least 50 percent of all liver transplants in
children and is characterized by the failure of the bile ducts
to develop normally and drain bile from the liver.
Several models to assess prognosis of liver disease have been developed. In acute liver failure leukocyte count, bilirubin, International Normalized Ratio (INR) and age have a strong correlation with outcome. In chronic liver failure, PELD (Pediatric end-stage liver disease) Score and the occurrence of complications of liver disease are important prognostic tools. Since the start of our own paediatric liver transplantation program at the University of Heidelberg in 2003, already 15 Children between 5 months and 14 years have been transplanted. Indications and outcome of these patients are reviewed in this paper.
|
Introduction
|
|---|
Liver transplantation has become a world-wide used method to
treat a variety of hepatic-based diseases. For the first time
liver transplantation was performed in 1963 by Dr. Thomas Starzl
at the University of Colorado, Denver in a three year old boy
with biliary atresia and end stage liver failure. In his memoirs
Dr. Starzl remembers:... Bennie's operation was on March 1 1963.......
However, nothing we had done could have prepared us for the
enormity of the task. Several hours were required just to make
the incision and enter the abdomen....... To make things worse,
Bennies blood would not clot....... He bled to death as we worked
desperately to stop the haemorrhage...." (Starzl T., Memoirs
of a transplant surgeon. The puzzle people 1992, Pittsburgh).
The patient did nor survive the operation. After that first
attempt three more transplantations were performed in Denver.
However, all three patients died during or shortly after the
operation. While the first patient died already in the operation
room, the second patient survived one week and third and last
patient of this period died after three weeks. At this point
Dr. Starzl stopped the transplantation program and returned
to his laboratory for important re-evaluation of his operation
procedure.
In 1967, the liver transplantation program in Denver restarted. Between 1967 and 1980, 86 children received a new liver at the pediatric liver transplantation program, University of Colorado. Initially the survival rate was about 30% for the first year [1]. The major problem was the high incidence of refractory acute and chronic rejections due to the limitation of immunosuppressive medications at that time. In 1976 this devastating situation was significantly changed after the discovery of the immunosuppressive activity of cyclosporine A by Borel and colleagues [2]. The introduction of cyclosporin into clinical practice in 1981 by Sir Calne [3] improved patient survival dramatically. Soon after that innovation liver transplantation programs developed successfully all over the world.
Since these early days when liver transplantation was still an experimental procedure in hopeless cases of severe liver failure, the outcome has dramatically improved to as much as 90% one year survival. The reasons for these changes are improvement of the surgical techniques [4] [5], modern superior immunosuppressive regimens [6], advanced bridging methods [7] and sophisticated peri- and postoperative intensive care [8]. Therefore, indications for pediatric liver transplantation have also changed over the years. Today, most young patients are in a more stable condition and referral to a transplantation center appears earlier in the course of liver disease. Besides the classical indications like biliary cirrhosis, acute liver failure and infectious hepatitis, new indications for transplantations are more and more defined.
But still, in chronic liver failure, the timing for transplantation might be as difficult as in acute liver failure. Many children with chronic liver disease are longer stable with a permanent risk of decompensation. Particularly in chronically ill children, criteria such as impaired growth rate under adequate enteral feeding, decreased liver synthesis and detoxification and major side effects of portal hypertension are playing an important role in the decision for a liver transplantation in a child.
|
The Heidelberg experience
|
|---|
In October 2003, a new liver transplantation program was started
as a concerted action of the medical disciplines at our university
[
9]. This team approach includes surgeons, pediatric radiologists,
pathologists, pediatricians, infectiologists and anesthesiologists.
After preparation of standard operation procedures for the various
disciplines, the first patient was allocated to
Eurotransplant in summer 2003. Up to date 15 children between 5 months and
14 years of age have been already transplanted in Heidelberg.
Currently the one year survival is 92% (one child died because
of a pre-existing fungal sepsis 3 days post transplantation).
Indications for liver transplantation were: Extrahepatic biliary
atresia, familial intrahepatic cholestasis syndrome, citrullinaemia
type I, hepatic manifestation of cystic fibroses, acute liver
failure (
Table 1) and arteriohepatic dysplasia (Alagille Syndrome).
One transplantation was done due to an drug resistant
Enterococcus faecium infection of a fibrotic liver in a girl with autosomal
recessive polycystic kidney disease (ARPKD) and Caroli-syndrome.
In the following we will delineate indications for transplantation
in these patients.
View this table:
[in this window]
[in a new window]
|
Table 1. The Heidelberg Paediatric Liver Transplantation Program (2003–2006). Patients are grouped according to the underlying diseases
|
|
|
Indications in detail
|
|---|
Biliary Atresia
The single most common cause for chronic liver failure in infancy
and childhood is biliary atresia. The incidence is 1 in 16 000
live births. Portoenterostomy (Kasai Procedure) is performed
in the majority of affected children. This may partially or
fully alleviate the jaundice, but it will not reverse the liver
damage that has already occurred or prevent any low-grade ongoing
damage. The Kasai procedure is successful in one-half of all
patients and if jaundice is fully relieved, most children will
grow and develop quite normally. After this procedure patients
often recover for some years, but until the age of 10 about
50% of the patients have to be transplanted due to chronic liver
failure [
10]. Cirrhosis generally occurs despite a successful
Kasai procedure. It seems of vital importance that the Kasai
Procedure is performed within 90 days after birth [
11]. Infants
older than 90 days may also benefit from Kasai operation, but
a careful histological examination should be done to identify
those with severe liver damage and to perform early transplantation
in these patients. Primary liver transplantation is usually
not indicated in patients with biliary atresia except for those
patients with signs of severe liver damage (coagulopathy, hypalbuminemia,
ascites).
In our own center 4 patients with biliary atresia (5 months to 14 years of age) have been transplanted so far (Table 1). The first two patients had a portoenterostomy performed within the first three months of life. Patient 1 had to be transplanted due to recurrent severe cholangitis and left the hospital 13 days after the uncomplicated transplantation. The second patient was re-transplanted because of refractory pruritus that could not be well controlled even with MARS dialysis. Albumin dialysis (MARS system) is characterized by the specific removal of albumin-bound toxins through an innovative membrane transport. In particular, the albumin acts as a specific molecular adsorbent that is regenerated on line in a recycling system. Nowadays MARS represents the most frequently used liver support system. This treatment has been shown to remove albumin-bound molecules, such as bilirubin, bile acids, aromatic amino acids and copper [12]. The postoperative course was uneventful. Patient 3 was a seven months old boy with therapy refractory ascites and acute-on-chronic liver failure. He was on haemodialysis for 4 weeks due to a hepatorenal syndrome. After transplantation he recovered slowly but today (2 years after transplantation) his liver enzymes are normal.). The fourth patient additionally suffered from Alagille syndrome (see below).
|
Intrahepatic bile duct paucity
|
|---|
Intrahepatic cholestasis secondary to paucity of bile duct is
an alteration of the anatomic integrity of the biliary tract.
It may lead to severe cholestasis of infancy. In children, intrahepatic
bile duct paucity may be syndromic (Alagille's) or nonsyndromic
(e.g., postviral, PSC). The nonsyndromic form may result from
infections in pregnancy (rubella, cytomegalie, hepatitis, chromosomal
abnormalities (trisomy 18 and 21, monosomy X) or metabolic disorders
such as cystic fibrosis or Zellweger's Syndrom. The Alagille
Syndrome has a specific pattern of malformations [
13]. It is
an autosomal dominant trait with cholestasis due to bile duct
paucity, vascular and cardiac anomalies (peripheral pulmonary
stenosis, atrial septal defect, ventricular septal defect, coarctation
of aorta, hypoplastic arteries), ocular malformations (deep-set
eyes, posterior embryotoxon, anterior chamber anomalies), typical
triangular face with broad forehead and butterfly-shaped vertebral
arch.
2 patients with Alagille Syndrome (patient 4 with additional biliary atresia) were transplanted at an age of 5 and 7 months respectively in Heidelberg (Table 1). In both patients transplantation was complicated by hypoplastic hepatic vessels (patient 4: hepatic artery, patient 5: hepatic artery and portal vein). Both had a peripheral pulmonary stenosis that did not cause any intra- or postoperative complications.
|
Progressive familial intrahepatic cholestasis
|
|---|
Progressive familial intrahepatic cholestasis (PFIC) is a chronic
cholestasis syndrome that begins in infancy and usually progresses
to cirrhosis within the first decade of life. Familial cholestasis
syndromes can be divided in two groups. Patients with severe
cholestasis and normal gamma glutamyl transferase (GGT) and
patients with elevated GGT. The first group comprises the original
family, an Amish family of danish origin named Byler [
14] and
those patients with a similar defect of the bile salt transporter
pump that are no offspring off the Byler family (PFIC 2). It
is important to keep in mind that the same constellation (severe
progressive cholestasis and normal GGT) is presented by patients
with inherited defects of bile acid synthesis, a group of disorder
very well amendable to rational specific therapy. In patients
with elevated GGT and progressive intrahepatic cholestasis a
defect of the MDR 3 receptor leads to cholestasis [
15]. In patients
with PFIC, therapeutic options are still limited. Biliary diversion
sometimes leads to a relief of the severe pruritus. If this
operation fails, liver transplantation is the only option. In
our Hospital, one patient with a PFIC 2 defect was transplanted
(
Table 1). It was a 3 year old boy who suffered from severe
pruritus despite biliary diversion received a cadaveric split
organ. Transplantation was performed without any major complications.
He did not develop any episode of diarrhoea, which is a well
described phenomenon after transplantation in patients with
PFIC. Two years after transplantation this patient is in a wonderful
condition.
|
Acute liver failure
|
|---|
Acute liver failure is defined as the onset of hepatic encephalopathy
and coagulopathy within 8 weeks of the onset of liver disease.
A pre-existing chronic liver disease by definition excludes
acute liver failure. Acute liver failure based on a chronic
liver disease is called acute on chronic liver failure. There
are several limitations to this very specific definition of
acute liver failure. The definition of encephalopathy in infants
and small children is often difficult or impossible to make.
In addition, acute liver failure in this age group might be
due to a formerly unknown inborn error of metabolism or an autoimmune
hepatitis. Acute liver failure in children is mainly caused
by viral, fungal or bacterial infections. In a large retrospective
study Kelly and co-workers described that about 50% of acute
liver failure in paediatric patients was due to an infection
with more than half of these diseases being non-A-non-B-non-C-hepatitis
[
16]. Metabolic diseases presenting as acute liver failure were
mainly observed during the first 12 months of life except for
Wilsons disease that occurs later in life (5 years and above).
In the group of metabolic diseases, neonatal haemochromatosis,
respiratory chain defects and Thyrosinemia type 1 were most
common [
17,
18]. Acute liver failure is often fatal but on the
other hand also spontaneous recovery appears. The likelihood
of the latter depends on etiology and age. As expected multiple
different prognostic scores are existing. For example, coagulation
factor V concentration below 20% and hepatic encephalopathy
have been used by the Paris group to indicate the need for high
urgency liver transplantation in acute liver failure [
19]. The
criteria from King's College London have been revised recently
and comprise 4 factors: leukocyte count >9000/nl, bilirubin
13.8 mg/dl, age below 2 years and INR
4. If one of these factors
appears in a child with acute liver failure mortality rises
dramatically to 76%. In the case of the appearance of 2 factors
mortality rises to 93% and with the present of 4 factors mortality
is 100% [
20].
Careful observation of patients for signs of spontaneous regeneration is vital to identify those patients that can survive without transplantation even if they are already listed on high priority for a liver transplantation.
Since the beginning of our program 6 patients with an acute liver failure were admitted to our intensive care unit. One patient recovered spontaneously after the putative agent that caused the acute liver failure (erythromycin) was stopped. One patient died within 36 hours after admission while waiting for high urgency transplantation and one patient with a neonatal herpes simplex infection and signs of hemophagocytic lymphohistiocytosis was considered not transplantable. The other three patients (Table 1) received a new organ (patient 7 received a living donation from his father). No technical complications appeared. The acute liver failure in patient 9 was initially thought to be caused by valproate toxicity. However, a diagnosis of Alpers Huttenlocher disease, also known as progressive neuronal degeneration of childhood with liver disease (PNDC) or Alpers-Huttenlocher syndrome [21] [22], was made 6 months after transplantation and the boy died 13 months after transplantation due to intractable seizures. The other two patients are doing well one and two years after transplantation.
|
Metabolic diseases
|
|---|
Liver transplantation has become an accepted treatment for various
hepatic-based metabolic disorders. Two groups of inborn errors
of metabolism can be distinguished: diseases leading to structural
liver damage such as Wilson's disease or alpha-1-antitrypsin
deficiency and disorders with mainly extrahepatic consequences
such as urea cycle disorders or organic [
23]. In our center,
so far 3 patients with hepatic-based metabolic diseases have
been transplanted (
Table 1). Patient 8 presented at the age
of 10 years with acute liver failure as the initial presentation
of Wilson's disease. Treatment with D-penicillamine was started
and her overall clinical condition improved. However, severe
coagulopathy persisted and coagulation factors had to be substituted
on a daily basis. Four weeks after admission she became encephalopathic
and had to be transplanted. One boy with citrullinaemia (patient
10) was listed for liver transplantation because of recurrent
metabolic crises and impending neurological damage. The peri-
and postoperative course was uncomplicated, especially episodes
of metabolic derangement could be avoided. Primary hyperoxaluria
type 1 (PH1) is a rare condition in which deficiency of the
liver enzyme alanine:glyoxylate aminotransferase leads to renal
failure and systemic oxalosis. One patient with PH1 was retransplantated
(patient 11) at our center after complicated combined liver/kidney
transplantation in another Transplantation Center 4 months before.
In patients with PH1, overproduction of oxalate due to deficiency
or mistargeting of hepatic alanine glyoxylate aminotransferase
leads to end stage renal disease. Patients with pyridoxine-resistant
forms of PH1 usually require organ replacement therapy, i.e.
liver transplantation to supply the deficient enzyme and/or
kidney transplantation to replace the affected organ [
24]. Our
patient received a combined liver and kidney transplantation
in a different center. His medical course was complicated by
hepatic artery thrombosis. The patient suffered from a fungal
sepsis and abscess formation of the biliary tract. He was in
extremely poor condition and liver transplantation was considered
as a rescue therapy to remove the untreatable septic focus.
Sadly he died 2 days after full organ cadaveric liver transplantation
because of spreading fungal infection unresponsive to any antifungal
treatment.
|
Cystic fibrosis
|
|---|
Cystic fibrosis (CF) is caused by a defect in the cystic fibrosis
transmembrane regulator (CFTR). Beyond the respiratory organs,
CFTR is also present in the ephitelium of the bile ducts. Therefore
CFTR defects may lead to severe liver disease mainly due to
inspissated bile in the small bile ducts causing focal fibrosis
and mucus plugging in the further course. This bile duct obstruction
is followed by an often unrecognized development of cirrhosis
and portal hypertension. The sequel of portal hypertension (esophageal
varices, hypersplenism, ascites) may threaten the lives of patients
with CF. This scenario mainly appears in prepubertal children.
About 5% of infants and children with CF develop liver disease.
To date the only therapy of patients with CF and liver disease
is modification of bile flow by using ursodesoxycholic acid
(
25). Liver transplantation in patients with CF has been successfully
performed in many centers all over the world [
26,
27].
After transplantation there is even some evidence that pulmonary symptoms may improve. This might be due to additional antiinflammatory potential of the immunosuppressive agents used after transplantation and an improvement of intrapulmonary shunting after liver transplantation. In our program, one patient with CF was transplanted at the age of 7 years because of recurrent upper gastrointestinal bleeding from oesophageal varices (patient 12). Complications after transplantation were severe ascites lasting for 18 months despite adequate treatment and a stenosis of the bile duct anastomosis. With a stent implantation and repeated endoscopic bile duct dilatation this stenosis was treated for 12 months. Now, two and a half years after transplantation the patient is doing very well and liver function is stabile and normalized.
|
Portal hypertension
|
|---|
Portal hypertension develops when blood flow through the liver
is obstructed. Posthepatic obstruction of the liver veins causes
Budd Chiari syndrome, intrahepatic obstruction may develop in
liver fibrosis or cirrhosis, and prehepatic obstruction is usually
caused by portal vein thrombosis. In a cohort of children with
acute bleeding episodes from esophageal varices, nearly 40%
had a portal vein thrombosis [
28]. Portal hypertension can be
managed conservatively by endoscopic sclerotherapy or banding
of the varices and ß-Blocker therapy reducing portal
blood flow and pressure. Depending on the underlying disease,
the course of portal hypertension can be stable without significant
episodes of upper gastrointestinal bleeding during childhood.
Especially in patients with a portal vein obstruction bleeding
episodes occur less often than in patients with ongoing fibrotic
changes of the liver as in biliary atresia. These patients are
much more likely to develop bleeding from portal hypertension.
In our hospital, one patient was transplanted because of recurrent
upper gastrointestinal bleeding and liver cirrhosis that had
developed after chemotherapy for non-Hodgkin lymphoma (patient
13). Another patient was transplanted for recurrent lower GI
Bleeding originating from portosystemic collaterals in the small
intestine (patient 14).
|
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
|
|---|
Patients with ARPKD that survive the neonatal period and the
sequel of lung hypoplasia develop liver fibrosis of variable
extent. The fibrosis is usually not progressive and causes little
or no problems in childhood. Several case reports describe children
with ARPKD and Caroli's syndrome [
29]. These patients have a
higher risk of developing cholangitis from the hepatic cysts.
Recently we have transplanted a 22 month old girl with ARPKD,
dialysis treatment and Caroli's syndrome (patient 15). The child
had developed repeated severe bacterial sepsis caused by
Enterococcus faecium, repeatedly detected in liver biopsies. Despite continues
treatment over a period of more than 6 months septic infection
always occurred 2 to 6 days after withdrawal of any antibiotic
therapy. In this situation a liver transplantation was considered
as the only curative treatment for this girl. 4 months after
TPL no infections reoccurred. Until today the patient is doing
fine.
|
Conclusions
|
|---|
Liver transplantation is a save technique for end stage liver
failure as well as in selective patients with acute liver failure.
The most common indications for liver transplantation are cholestatic
diseases, metabolic diseases and acute liver failure. Since
timing of the operation, peri- and postoperative care may be
extremely difficult in the individual cases, a truly interdisciplinary
approach is mandatory.
Conflict of interest statement. None declared.
|
References
|
|---|
- Bismuth H, Castaing D, Ericzon BG, et al. Hepatic transplantation in Europe. First Report of the European Liver Transplant Registry. Lancet (1987) 2:674–676.[ISI][Medline]
- Borel JF, Feurer C, Gubler HU, Stahelin H. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions (1976) 6:468–475.[CrossRef][ISI][Medline]
- Calne RY, White DJ, Evans DB, et al. Cyclosporin A in cadaveric organ transplantation. Br Med J (Clin Res Ed) (1981) 282:934–936.[Medline]
- Belghiti J, Sauvanet A, Panis Y, Gayet B, Fekete F. Transplantation hepatique sans clampage de la veine cave inferieure. Presse Med (1992) 21:569–571.[ISI][Medline]
- Belghiti J, Panis Y, Sauvanet A, Gayet B, Fekete F. A new technique of side to side caval anastomosis during orthotopic hepatic transplantation without inferior vena caval occlusion. Surg Gynecol Obstet (1992) 175:270–272.[Medline]
- Kelly D, Jara P, Rodeck B, et al. Tacrolimus and steroids versus ciclosporin microemulsion, steroids, and azathioprine in children undergoing liver transplantation: randomised European multicentre trial. Lancet (2004) 364:1054–1061.[CrossRef][ISI][Medline]
- Debray D, Yousef N, Durand P. New management options for end-stage chronic liver disease and acute liver failure: potential for pediatric patients. Paediatr Drugs (2006) 8:1–13.[CrossRef][Medline]
- Ganschow R, Nolkemper D, Helmke K, et al. Intensive care management after pediatric liver transplantation: a single-center experience. Pediatr Transplant (2000) 4:273–279.[CrossRef][Medline]
- Engelmann G, Meyburg J, Schmidt J, Lenhartz H. Pediatric liver transplantation. Introduction of a program for southern Germany in Heidelberg. Clin Transplant (2006) 20(Suppl 17):124–130.[CrossRef][ISI][Medline]
- Chardot C, Carton M, Spire-Bendelac N, Le Pommelet C, Golmard JL, Auvert B. Prognosis of biliary atresia in the era of liver transplantation: French national study from 1986 to 1996. Hepatology (1999) 30:606–611.[CrossRef][ISI][Medline]
- Chardot C, Carton M, Spire-Bendelac N, et al. Is the Kasai operation still indicated in children older than 3 months diagnosed with biliary atresia? J Pediatr (2001) 138:224–228.[CrossRef][ISI][Medline]
- Saliba F. The Molecular Adsorbent Recirculating System (MARS) in the intensive care unit: a rescue therapy for patients with hepatic failure. Crit Care (2006) 10:118.[CrossRef][Medline]
- Alagille D, Odievre M, Gautier M, Dommergues JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr (1975) 86:63–71.[CrossRef][ISI][Medline]
- Clayton RJ, Iber FL, Ruebner BH, et al. Byler disease. Fatal familial intrahepatic cholestasis in an Amish kindred. Am J Dis Child (1969) 117:112–124.[Medline]
- Keitel V, Burdelski M, Warskulat U, et al. Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis. Hepatology (2005) 41:1160–1172.[CrossRef][ISI][Medline]
- Lee WS, McKiernan P, Kelly DA. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United Kingdom. J Pediatr Gastroenterol Nutr (2005) 40:575–581.[CrossRef][ISI][Medline]
- Lee WS, McKiernan P, Kelly DA. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United Kingdom. J Pediatr Gastroenterol Nutr (2005) 40:575–581.[CrossRef][ISI][Medline]
- Squires RHJ, Shneider BL, Bucuvalas J, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr (2006) 148:652–658.[CrossRef][ISI][Medline]
- Pauwels A, Mostefa-Kara N, Florent C, et al. Emergency liver transplantation for acute liver failure. Evaluation of London and Clichy criteria. J Hepatol (1993) 17:124–127.[CrossRef][ISI][Medline]
- Dhawan A, Cheeseman P, Mieli-Vergani G. Approaches to acute liver failure in children. Pediatr Transplant (2004) 8:584–588.[CrossRef][ISI][Medline]
- Delarue A, Paut O, Guys JM, et al. Inappropriate liver transplantation in a child with Alpers-Huttenlocher syndrome misdiagnosed as valproate-induced acute liver failure. Pediatr Transplant (2000) 4:67–71.[CrossRef][Medline]
- Kayihan N, Nennesmo I, Ericzon BG, et al. Fatal deterioration of neurological disease after orthotopic liver transplantation for valproic acid-induced liver damage. Pediatr Transplant (2000) 4:211–214.[CrossRef][Medline]
- Meyburg J, Hoffmann GF. Liver transplantation for inborn errors of metabolism. Transplantation (2005) 80:S135–S137.[CrossRef][ISI][Medline]
- Leumann E, Hoppe B. Pre-emptive liver transplantation in primary hyperoxaluria type 1: a controversial issue. Pediatr Transplant (2000) 4:161–164.[CrossRef][Medline]
- Colombo C, Russo MC, Zazzeron L, Romano G. Liver disease in cystic fibrosis. J Pediatr Gastroenterol Nutr (2006) 43(Suppl 1):S49–S55.[ISI][Medline]
- Molmenti EP, Squires RH, Nagata D, et al. Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population. Pediatr Transplant (2003) 7:93–97.[CrossRef][ISI][Medline]
- Melzi ML, Kelly DA, Colombo C, et al. Liver transplant in cystic fibrosis: a poll among European centers. A study from the European Liver Transplant Registry. Transpl Int (2006) 19:726–731.[CrossRef][ISI][Medline]
- Price MR, Sartorelli KH, Karrer FM, Narkewicz. MR, Sokol RJ, Lilly JR. Management of esophageal varices in children by endoscopic variceal ligation. J Pediatr Surg (1996) 31:1056–1059.[CrossRef][ISI][Medline]
- De Kerckhove L, De Meyer M, Verbaandert C, et al. The place of liver transplantation in Caroli's disease and syndrome. Transpl Int (2006) 19:381–388.[CrossRef][ISI][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
Top
Abstract
Introduction