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Pediatric Recipient Considerations

  • Mar Miserachs
  • Vicky Lee Ng
Reference work entry
Part of the Organ and Tissue Transplantation book series (OTT)

Abstract

Timely patient referral to an experienced pediatric liver transplant program should occur before the development of any contraindication or life-threatening complications. Selection of the potential pediatric candidate for liver transplant via a multidisciplinary evaluation process is key in achieving an ideal outcome for each and every patient. Unrecognized reversible medical conditions, alternative medical or surgical therapies and contraindications for liver transplant, will be identified. This chapter focuses on the evaluation of the patient for liver transplantation and provides an overview of the indications and contraindications for pediatric liver transplantation.

Keywords

Liver transplantation Indications Contraindications Evaluation Referral, timing Children Biliary atresia 

Introduction

Liver transplantation is lifesaving for a number of life-threatening chronic and acute liver conditions in children. Children may present with unique diseases, clinical susceptibilities, physiological responses, and special neurodevelopmental features that distinguish them from adults. Timely referral to an experienced pediatric liver transplant program will address the challenges of patient selection via a multidisciplinary evaluation process and individualized assessment plan, toward an overarching goal of achieving an ideal outcome for each and every patient. Indications and contraindications for liver transplant and the most common etiologies leading to transplant are also reviewed in this chapter.

Pre-liver Transplant Assessment

Pretransplant assessment enables identification of patients with unrecognized reversible medical conditions, those who may benefit from alternative medical or surgical therapies and those with contraindications for liver transplant. The ultimate goal of such an evaluation process is to obtain an adequately timed consensus decision regarding patient’s candidacy and suitability for liver transplantation. Concurrent goals include identifying opportunities to optimize medical therapy, maximize nutritional support, accelerate immunizations, and enable and facilitate adequate family education and support (see Table 1).
Table 1

Goals of the pre-liver transplant assessment process

Confirm the patient’s primary diagnosis, assess presence and contribution of associated systemic manifestations or comorbidities, prognosticate natural history of primary condition with and without transplantation as therapy

Identify additional medical or nontransplant surgical opportunities to maximize current therapy

Establish severity of disease, urgency for liver transplant

Determine and identify any absolute or relative contraindications

Identify any complicating factors or comorbidities that may limit tolerance to the stress of the surgery

Consider technical limitations for a successful operation and/or identify contraindications for liver transplant

Determine appropriateness for living donor liver transplantation

Assess patient’s nutritional status and implement aggressive strategies for nutritional rehabilitation

Evaluate, complete, and accelerate if required the immunization schedule (live vaccines will not be given after liver transplantation)

Develop a trusting relationship between the child, family, and transplant team

Ensure an informed decision from patient and family to proceed with liver transplantation

Provide education regarding donor organ allocation, the waiting list, and ensure adequate localization and transport logistics for when a potential liver graft is available

To provide information regarding health care plan/drug coverage costs and needs

Anticipate potential challenges that may arise posttransplant including adherence to treatment and compliance with medical advice following liver transplantation

Assessing the potential liver transplant candidate is a complex and thorough process that begins with recognition of patient’s underlying disease and comorbidities. An individualized evaluation plan that will include multiple investigations and consultations will be tailored according to the needs of each potential candidate. This process can take from a couple of days to few weeks or even months, depending on patient acuity and severity of disease.

The evaluation includes specific blood work (blood group, cell blood counts, coagulation tests, liver function, renal function, nutrition profile, and infectious serologies), radiographic studies (abdominal ultrasound, echocardiogram, and chest radiograph) and electrocardiography. Additional testing may be required to further investigate specific underlying diagnoses or comorbidities. For example, children with syndromic variants of biliary atresia may require abdominal computerized tomography angiography in anticipation of any technical modifications needed during surgery (as such as in the setting of identifying an interrupted inferior vena cava) (Varela-Fascinetto et al. 1998). A detailed renal function assessment is recommended in patients with primary liver conditions predisposing to renal dysfunction, including Alagille syndrome or metabolic liver disease, as renal-sparing immunosuppression protocols may be recommended posttransplantation (Kamath et al. 2012).

The expertise and insights provided by the spectrum of multidisciplinary and experienced team members as well as the patient’s primary and/or referring physician are paramount. The spectrum of team members meeting with a patient and family at pre-liver transplant candidacy assessment include: a liver transplant surgeon, a pediatric hepatologist, anesthesiologist, critical care specialist, infectious disease specialist, transplant coordinator, dietitians, pharmacist, physiotherapists, social worker, and psychologist. Consultation with other specialists and allied-health members may be required based on an individualized basis. The recently published American Association for the Study of Liver Diseases (AASLD) Clinical Practice Guidelines for “Evaluation of the pediatric patient for liver transplantation” recommended referral of patients with end-stage liver disease for a careful oral examination aimed at revealing any abnormalities such as dental caries or gingival disease for earlier intervention and optimization of oral hygiene (Shiboski et al. 2009; Squires et al. 2014).

Patients with chronic liver disease are at risk for poor growth, malnutrition and fat-soluble vitamin deficiencies, particularly those with cholestatic liver conditions such as biliary atresia, Alagille syndrome, or progressive familial intrahepatic cholestasis (PFIC) (DeRusso et al. 2007). Nutritional assessment is a key component of the pre-transplant evaluation process since it allows opportunities for intervention (Carter-Kent et al. 2007; DeRusso et al. 2007). Earliest aggressive nutritional support, such as nasogastric feeding or parenteral nutrition in patients with biliary atresia, is known to affect the pre- and posttransplant survival outcomes and neurodevelopmental outcomes. Commonly used variables including anthropometrics may not be sufficiently accurate in assessing a patient’s nutritional status. For instance, serial weight increases may reflect worsening ascites or hepatosplenomegaly and not necessarily a better nutritional status. Instead, measured triceps skinfolds and mid-upper arm circumference, which can be compared to normative data, will provide a better estimation of nutrition status in patients with chronic liver disease (Sokol and Stall 1990).

Timing and Criteria for Patient Referral

Timely referral for liver transplant should ideally occur before the development of contraindications and in those at increased risk for life-threatening clinical complications. Earliest referrals will allow a detailed evaluation of the potential candidate and optimization of the timing for liver transplant. Anticipatory and/or earliest referrals are beneficial in patients with unresectable hepatoblastoma, metabolic liver diseases refractory or challenging to medical therapy, and patients with acute liver failure.

The AASLD, and endorsed by the American Society of Transplantation (AST) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) recently published a clinical practice guideline for the evaluation of the pediatric patient for liver transplantation. Important findings about the timing and criteria for patient referrals will be highlighted below (Squires et al. 2014).

Indications for Liver Transplantation

The liver is a multifunctional organ that it is involved in a number of critical excretory (bile flow formation), synthetic (albumin and clotting factors), metabolic (glucose homeostasis), and hemodynamic functions (portal blood flow). Impairment in one or more of these areas will result in disease and eventually in the need for liver transplantation (Kamath and Olthoff 2010). The number of diseases for which liver transplantation has been performed in children has expanded since the early years of liver transplantation. Frequencies of primary diagnosis of 2702 pediatric liver transplant recipients in Studies of Pediatric Liver Transplantation (SPLIT), a North American multicenter registry, are shown in Table 2.
Table 2

Primary diagnosis for liver transplantation: Studies of Pediatric Liver Transplant (SPLIT) Registry 1995–2007

Total number

2702

Cholestatic liver disease

1457 (53.9 %)

Biliary atresia

1116

Alagille syndrome

76

Primary sclerosing cholangitis

67

Total parenteral nutrition-induced

48

Familial cholestasis

40

Idiopathic cholestasis/cirrhosis

28

Neonatal hepatitis

28

Biliary strictures

3

Other

51

Metabolic disease

405 (15 %)

Alpha-1 antitrypsin deficiency

82

Urea cycle defect

67

Cystic fibrosis

42

Wilson disease

31

Tyrosinemia

31

Glycogen storage disease

21

Crigler-Najjar syndrome

18

Gestational alloimmune liver disease

16

Primary hyperoxaluria

8

Inborn error of bile acid metabolism

3

Other

86

Acute liver failure

379 (14 %)

Unknown etiology

291

Autoimmune hepatitis

43

Acute-subacute hepatitis A,B,C

9

Other

36

Cirrhosis/end-stage liver disease

182 (6.7 %)

Autoimmune hepatitis/cirrhosis

84

Unknown

49

Neonatal hepatitis/cirrhosis

14

Hepatitis C cirrhosis

14

Other

21

Tumor

180 (6.7 %)

Hepatoblastoma

128

Hepatocellular carcinoma

21

Hemangioendothelioma

18

Other

13

Toxicity

20 (0.7 %)

Drug induced

11

Accidental overdose

6

Attempted suicide

2

Other

1

Other

79 (2.9 %)

Congenital hepatic fibrosis

16

Budd-Chiari syndrome

13

Other

50

At the time of evaluation for liver transplantation and regardless of the primary diagnosis, patients will present with one or more of the following indications: (1) cholestatic liver disease; (2) chronic end-stage liver disease with liver synthetic dysfunction and/or complications of portal hypertension; (3) acute liver failure; (4) unressectable liver tumors, including vascular malformations such as hepatic hemangioendothelioma; and/or (5) metabolic disease (Whitington and Balisteri 1991).

Contraindications to Liver Transplant

Liver transplantation should not be offered in those circumstances in which liver transplant has consistently lead to poor patient and graft outcomes. Absolute contraindications to transplantation include: (1) generalized extrahepatic malignancy with the exception of hepatoblastoma with isolated pulmonary metastases; (2) uncontrolled systemic infection; (3) progressive terminal nonhepatic disease; (4) severe portopulmonary hypertension not responsive to medical therapy; and (5) severe, irreversible neurologic injury (Whitington and Balisteri 1991; Kamath and Olthoff 2010; Squires et al. 2014).

Relative contraindications to liver transplant constitute those situations in which the risks of transplantations may be outweighed by other considerations or mitigated by other interventions before listing. With improved understanding on the pathophysiology and treatment of diseases, previously considered absolute contraindications to transplant such as hemophagocytic lymphohistiocytosis are now accepted as relative contraindications to be determined by pediatric liver transplant programs on a case-by-case basis (Amir et al. 2016). Absolute and relative contraindications to liver transplant are shown in Table 3.
Table 3

Contraindications to liver transplant

Absolute

 Generalized extrahepatic malignancy with the exception of hepatoblastoma with isolated pulmonary metastases

 Uncontrolled systemic infection

 Progressive terminal nonhepatic disease including valproate-induced liver failure (Alper’s disease) or Niemann-Pick disease type C

 Severe portopulmonary hypertension not responsive to medical therapy

 Severe, irreversible neurologic injury

Relative

 Hepatocellular carcinoma with venous invasion or rapid progression despite chemotherapy

 Hemophagocytic lymphohistiocytosis (HLH)

 Acquired immunodeficiency syndrome (AIDS)

 Severe psychosocial abnormalities including high certainty of nonadherence despite multidisciplinary interventions and support

Etiology

Describing all the etiologies leading to liver transplantation in children is far beyond the purpose of this text. Instead, broad listing indications for liver transplantation are revised.

Cholestatic Liver Diseases

This group includes a wide variety of etiologies such as biliary atresia, Alagille syndrome, or PFIC. Irrespective of the cause, children with cholestatic chronic liver diseases are often referred for liver transplantation candidacy assessment and patient selection with similar onset or concerns of impending complications. These include growth failure, severe malnutrition, intractable pruritus, or hepatic osteodystrophy. Complications derived from portal hypertension or hepatic insufficiency may also be present at the time of liver transplant assessment.

Biliary Atresia is a progressive, idiopathic, fibro-obliterative disease of the extrahepatic biliary tree that presents with biliary obstruction exclusively in the neonatal period (Balisteri et al. 1996). The overall incidence is low (about 1:10,000 to 1:20,000 live births). Hepatoportoenterostomy within the first 60 days of life should be the primary surgical intervention. Although surgical intervention improves survival, biliary atresia remains the most common pediatric indication for liver transplantation worldwide (Hartley et al. 2009). Children with syndromic variants of biliary atresia may present with anatomical variations such as interrupted inferior vena cava or splenic malformations. Abdominal vascular imaging performed at time of evaluation for transplantation may allow anticipation of any technical modifications that may be needed during surgery (Varela-Fascinetto et al. 1998).

Liver transplantation in children with biliary atresia should be considered when one or more of the following: (1) patients with late initial presentation (>120 days of age) and advanced cirrhosis on liver biopsy or unfavorable course; (2) lack of reestablishment of biliary drainage after the hepatoportoenterostomy with a total bilirubin greater than 6 mg/dL (102.6 μmol/L) beyond 3 months from hepatoportoenterostomy; (3) complications derived from profound cholestasis; (4) recurrent episodes of ascending cholangitis; and (5) cirrhosis with signs of liver insufficiency or complications of portal hypertension (Shneider et al. 2006).

Other cholestatic conditions such as Alagille syndrome or PFIC type 1 and 2 will present similarly at time of liver transplant assessment. Other indications for liver transplant in these primary conditions include severe pruritus refractory to medical or surgical therapy (biliary diversion or ileal exclusion), marked osteodystrophy with bone fractures, xanthomata, or more rarely, the evidence of hepatic malignancy – hepatocellular carcinoma.

Alagille syndrome is an autosomal dominant disorder, which may present with characteristic facial features and hepatic, cardiac (most often peripheral pulmonary artery stenosis), skeletal (typically butterfly vertebrae), renal, vascular or ophthalmologic involvement. Extrahepatic manifestations of Alagille syndrome – mainly structural cardiac disease – have a significant impact on the outcome of liver transplantation. Hence, a careful and individualized pretransplant evaluation plan is warranted in this population. Vascular imaging of the abdomen – to investigate for any potential arterial stenosis or coarctation – and head and neck – to investigate for any vascular anomalies – before transplantation is recommended (Kamath et al. 2012).

Three types of PFIC have been identified which are autosomal recessive cholestatic conditions resulting from mutations in ATP8B1 (PFIC1), ABCB11 (PFIC2), and ABCB4 (PFIC3), respectively. Treatment with ursodeoxycholic acid is recommended. Timely intervention with partial external biliary diversion or ileal exclusion may relieve pruritus and slow disease progression in patients with PFIC1 and PFIC2. Given the extrahepatic expression of ATP8B1, clinical concerns often experienced by patients include intractable diarrhea, poor growth, recurrent pancreatitis, or graft steatohepatitis (Lykavieris et al. 2003). Indications for liver transplantation in PFIC1 include: biliary diversion failed or not timely performed. Unlike PFIC1, liver transplantation is curative for patients with bile salt export pump (BSEP) disease, formerly PFIC2 who do also present high risk of malignancy in the native liver (Lykavieris et al. 2003; Romano et al. 2011). Disease recurrence in patients with BSEP disease has been reported, which should be disclosed as part of the informed consent prior to transplant (Siebold et al. 2010).

Chronic End-Stage Liver Disease

Cirrhosis is a common outcome of different mechanisms and etiologies of chronic liver injury including Wilson’s disease, autoimmune hepatitis, primary sclerosing cholangitis, or cryptogenic cirrhosis. Its presence alone is not sufficient to warrant liver transplantation unless it presents with evidence of deteriorating liver synthetic function – hypoalbuminemia and/or uncorrectable coagulopathy – or decompensated portal hypertension, not manageable with maximal medical therapeutic interventions.

Common manifestations of decompensated cirrhosis include refractory ascites, hepatic encephalopathy, variceal hemorrhage, and spontaneous bacterial peritonitis. Other complications include hepatorenal syndrome, hepatopulmonary syndrome, or portopulmonary hypertension. The presence of any of these should lead to patient referral for liver transplant evaluation. Of note, severe portopulmonary hypertension not responsive to medical therapy is considered a contraindication for liver transplant (Squires et al. 2014).

In patients with liver disease associated with cystic fibrosis, variceal bleeding secondary to portal hypertension, in the absence of other signs of decompensated liver disease, requires careful consideration by an experienced liver transplant program as to the risks versus benefits of offering liver transplantation (Colombo et al. 2002). Liver transplantation in patients with cystic fibrosis should be reserved for patients who have evidence of hepatocellular dysfunction in addition to unmanageable complications of portal hypertension. Pre-liver transplant assessment in this unique patient population requires careful evaluation of the cardiopulmonary status, nutritional status, and bacterial or fungal respiratory colonization.

Patients with preexisting stable chronic liver diseases may present with acute-on-chronic liver failure, defined by an acute deterioration in liver function in addition to extrahepatic organ failure, after a precipitating event such as a bacterial or viral infection. Recognition of such clinical scenarios may be an appropriate trigger for referral to a transplant center.

Acute Liver Failure

Pediatric acute liver failure is a life-threatening illness in which a previously healthy child rapidly progresses to severe hepatic dysfunction and coagulopathy, which results in death or the need for liver transplantation nearly 50% of the time. Acute liver failure is not a single disease and is considered to be the final common pathway of a variety of insults to the liver. Etiologies differ widely among geography and age at presentation, and can be broadly categorized as infectious, immunologic, metabolic, and toxin/drug related (Dhawan 2012). Etiology of acute liver failure remains indeterminate in almost half of the cases (Squires et al. 2006).

Identification of pediatric acute liver failure as defined below should prompt an emergent consultation and referral to a pediatric liver transplant center. Acute liver failure can be defined following the inclusion criteria defined for the Pediatric Acute Liver Failure study by Squires et al. (2006): (1) absence of a known, chronic liver disease; (2) liver-based coagulopathy that is not responsive to parenteral vitamin K; (3) international normalized ratio (INR) between 1.5 and 1.9 with clinical evidence of encephalopathy or 2.0 and higher regardless of the presence of clinical encephalopathy. Hepatic-based encephalopathy usually is a late feature and is not essential for the diagnosis (Rivera-Penera et al. 1997).

One of the priorities of the evaluation process of a presenting child with acute liver insufficiency is identification of treatable conditions such as neonatal liver failure secondary to gestational alloimmune liver disease, acetaminophen toxicity, or autoimmune hepatitis. Another priority is to exclude genetic multisystem disorders such as valproate-associated liver failure, for which liver transplantation is contraindicated (Mindikoglu et al. 2011). In the absence of a single criterion that can predict the outcome of children with acute liver failure, there is a risk that some patients undergoing liver transplantation may have survived without it.

Tumors

Decision toward liver transplantation in children with liver tumors should occur in close collaboration with pediatric oncologists, radiologists, and even pathologists. Hepatoblastoma is the most common malignancy leading to liver transplantation in the pediatric population, followed by hepatocellular carcinoma and hepatic hemangioendothelioma, which are rare indications for transplant.

Gold standard treatment for hepatoblastoma is perioperative chemotherapy followed by complete resection of viable tumor (Malogolowkin et al. 2012). Liver transplant is indicated for patients with unresectable nonmetastatic hepatoblastoma and for those with cleared pulmonary metastasis after chemotherapy or pulmonary metastasis completely resected with tumor-free margins (Aronson et al. 2005). Children with unresectable hepatoblastoma, should be referred urgently for liver transplant evaluation.

Hepatocellular carcinoma is uncommon in children, and in comparison to the adult population, it is most commonly found in noncirrhotic livers (Yu et al. 2006). Cure is only achieved with resection and liver transplant should be early considered in the absence of extrahepatic disease.

Liver transplantation should be offered in children with hepatic hemangioendothelioma not responding to treatment or causing life-threatening complications such as high-output cardiac failure or coagulopathy (Kasabach-Merritt syndrome) (Squires et al. 2014).

Metabolic Liver Disease

Liver transplantation has evolved into an attractive approach for a growing number of liver-based metabolic diseases in a variety of clinical situations, even in the absence of structural liver disease (Kayler et al. 2002, 2003). In children with metabolic liver disease, transplant should be considered before any irreversible complications that would impose a contraindication for transplant occur (Stevenson et al. 2010). Indication and timing for liver transplantation for metabolic liver disease varies among different etiologies (Arnon et al. 2010). A clear understanding of the biology of the metabolic disease is critical to assess the potential impact of liver transplantation on the course of the disease (Mazariegos et al. 2014).

Critical questions that need to be addressed during the evaluation process of a patient with metabolic disease: (1) Does the patient have structural liver disease or is at increased risk for malignancy? (2) Is the metabolic defect confined to the liver or is it also expressed in other organs? (3) Will liver transplantation prevent, mitigate, or reverse the extrahepatic organ or central nervous system injury? (4) What are the clinical outcomes of the metabolic defect if not corrected? (5) Are there any other effective therapies to mitigate risks without transplantation?

Metabolic liver diseases potentially leading to liver transplant can be grouped in the following categories (see Table 4) (Mazariegos et al. 2014):
Table 4

Metabolic diseases for which liver transplant has been reported (With permission from Mazariegos et al. 2014)

Diseases with structural liver disease

Metabolic defect mainly expressed in the liver

Metabolic defect expressed in other organs or tissues

 Alpha-1 antitrypsin deficiency

 Wilson disease

 Tyrosinemia type I

 Cystic fibrosis

 Glycogen storage disease Type IV (GBE1 gene)

 PFIC1

 PFIC2

 Glycogen storage disease types Ib, III, and IV

 PFIC3

 Nonalcoholic steatohepatitis

 Primary bile acid synthesis disorders

 Gaucher disease, Niemann–Pick disease

 Hepatic porphyrias

 Cholesterol ester storage disease

 Acute intermittent porphyria

 Mitochondrial cytopathies

 Variegate porphyria

 Cerebrotendinous xanthomatosis

 Glycogen storage disease type Ia

 Citrin deficiency

 Hereditary fructose intolerance

 Erythropoietic porphyria

 Indian childhood cirrhosis

 

Diseases without structural liver disease

Metabolic defect mainly expressed in the liver

Metabolic defect expressed in other organs or tissues

 Crigler–Najjar syndrome type 1

 Citrulinemia

 Primary hyperoxaluria

 Cystinosis

 Urea cycle disorders

 Branched amino acids disorders

 Familial hypercholesterolemia

 Organic acidemias:

 Fatty acid oxidation defects

  Propionic acidemia

 Coagulation defects:

  Methylmalonic acidemia

  Hemophilia A

  Mevalonicacidemia

  Factors V and VII deficiency

  Maple syrup urine disease

  Proteins C and S deficiencies

 

 Factor H deficiency

 

 Afibrinogenemia

 

 Amyloidosis type 1

 
  1. 1.
    Diseases with structural liver disease with:
    1. (a)

      Metabolic defect mainly expressed in the liver

       
    2. (b)

      Metabolic defect expressed in other organs or tissues

       
     
  2. 2.
    Diseases with normal liver parenchyma with:
    1. (a)

      Metabolic defect mainly expressed in the liver

       
    2. (b)

      Metabolic defect expressed in other organs or tissues

       
     

Retransplantation

Review of the SPLIT database was revealing for a 11.2% rate of re-liver transplantation among 1611 pediatric patients who underwent primary liver transplantation in a pediatric liver transplant program in the United States or Canada during a 9-year study period. The most common causes of graft failure during the first 30 postoperative days were vascular complications (46.7%) and primary graft dysfunction (43.9%). Patient survival outcomes were worse in patients requiring early re-liver transplantation (Ng et al. 2008).

Among SPLIT subjects alive after 1 year from liver transplantation, the most common cause of late graft loss is acute and chronic rejection (48.5%) followed by the chronic effects of hepatic arterial thrombosis (11.4%) and biliary strictures (8.6%) (Soltys et al. 2007).

Recurrence of Primary Disease After Liver Transplantation

Relapse of primary disease after liver transplant in children is rare, and it is limited to patients who have received a transplant for autoimmune liver diseases, PFIC2, and malignancy. In patients transplanted for hepatic malignancy, a combined oncology and pediatric liver transplant medical-surgical follow-up management is recommended.

Autoimmune liver diseases potentially leading to transplantation include autoimmune hepatitis, autoimmune sclerosing cholangitis, and primary sclerosing cholangitis (Mieli-Vergani and Vergani 2011). Disease recurrence in the graft is a well-recognized complication in this group of patients (Chai et al. 2010). Consequently, patients may require maintenance of a low-dose steroid-based immunosuppression regimen, compared to the typical standard of steroid-free status by 3–6 months following liver transplantation for the majority of other pediatric indications.

Recurrence of low GGT cholestasis mimicking BSEP disease following liver transplantation has been reported in patients with ABCB11 mutations. Recurrent BSEP deficiency in the liver graft is often associated with poor response to treatment and is accompanied by significant morbidity and mortality (Siebold et al. 2010).

Conclusion

Adequate and timely referral of the potential candidate to an experienced pediatric liver transplant center is an important and fundamental element toward achieving the overarching goal of an ideal outcome for children requiring liver transplantation. Given the increasing spectrum of conditions that may benefit from liver transplantation as a lifesaving intervention amidst the supply–demand imbalance challenges experienced by liver transplant programs worldwide, the patient selection process and recipient considerations by a skilled multidisciplinary team are critical elements in the journey towards the overarching goal of keeping the “ideal” end in mind – optimizing both quantity and quality of life-years restored by life-saving liver transplantation.

Cross-References

References

  1. Amir AZ, Ling SC, Naqvi A et al. (2016) Liver transplantation for children with acute liver failure associated with secondary hemophagocytic lymphohistiocytosis. Liver Transpl 22:1245–1253.CrossRefPubMedGoogle Scholar
  2. Arnon R, Kerkar N, Davis MK et al (2010) Liver transplantation in children with metabolic diseases: the studies of pediatric liver transplantation experience. Pediatr Transplant 14:796–805CrossRefPubMedGoogle Scholar
  3. Aronson DC, Schnater JM, Staalman CR et al (2005) Predictive value of the pretreatment extent of disease system in hepatoblastoma: results from the International Society of Pediatric Oncology Liver Tumor Study Group SIOPEL-1 study. J Clin Oncol 23:1245–1252CrossRefPubMedGoogle Scholar
  4. Balisteri WF, Grand R, Hoofnagle JH et al (1996) Biliary atresia: current concepts and research directions. Summary of a symposium. Hepatology 23:1682–1692CrossRefGoogle Scholar
  5. Carter-Kent C, Radhakrishnan K, Feldstein AE (2007) Increasing calories, decreasing morbidity and mortality: is improved nutrition the answer to better outcomes in patients with biliary atresia? Hepatology 46:1329–1331CrossRefPubMedGoogle Scholar
  6. Chai PF, Lee WS, Brown RM et al (2010) Childhood autoimmune liver disease: indications and outcome of liver transplantation. J Pediatr Gastroenterol Nutr 50:295–302CrossRefPubMedGoogle Scholar
  7. Colombo C, Battezzati PM, Crosignani A et al (2002) Liver disease in cystic fibrosis: a prospective study on incidence, risk factors and outcome. Hepatology 36:1374–1382CrossRefPubMedGoogle Scholar
  8. Dhawan A (2012) Acute liver failure in children and adolescents. Clin Res Hepatol Gastroenterol 36:278–283.CrossRefPubMedGoogle Scholar
  9. DeRusso PA, Ye W, Shepherd R et al (2007) Growth failure and outcomes in infants with biliary atresia: a report from the Biliary Atresia Research Consortium. Hepatology 46:1632–1638CrossRefPubMedGoogle Scholar
  10. Hartley JL, Davenport M, Kelly DA (2009) Biliary atresia. Lancet 374:1704–1713CrossRefPubMedGoogle Scholar
  11. Kamath BM, Olthoff KM (2010) Liver transplantation in children: update 2010. In: Ng VL, Feng S (eds) Optimization of outcomes for children after solid organ transplantation, vol 57, Pediatric Clinics of North America. Saunders, Philadelphia, pp 401–414Google Scholar
  12. Kamath BM, Yin W, Miller H et al (2012) Outcomes of liver transplantation for patients with Alagille syndrome: the studies of pediatric liver transplantation experience. Liver Transpl 18:940–948CrossRefPubMedGoogle Scholar
  13. Kayler LK, Merion RM, Lee S et al (2002) Long-term survival after liver transplantation in children with metabolic disorders. Pediatr Transplant 6:295–300CrossRefPubMedGoogle Scholar
  14. Kayler LK, Rasmussen CS, Dykstra DM (2003) Liver transplantation in children with metabolic disorders in the United States. Am J Transplant 3:334–339CrossRefPubMedGoogle Scholar
  15. Lykavieris P, van Mil S, Cresteil D et al (2003) Progressive familial intrahepatic cholestasis type 1 and extrahepatic features: no catch-up of stature growth, exacerbation of diarrhea, and appearance of liver steatosis after liver transplantation. J Hepatol 39:447–452CrossRefPubMedGoogle Scholar
  16. Malogolowkin MH, Katzenstein HM, Krailo M et al (2012) Treatment of hepatoblastoma: the North American cooperative group experience. Front Biosci (Elite Ed) 4:1717–1723CrossRefGoogle Scholar
  17. Mazariegos G, Shneider B, Burton B et al (2014) Liver transplantation for pediatric metabolic disease. Mol Genet Metab 111:418–427CrossRefPubMedGoogle Scholar
  18. Mieli-Vergani G, Vergani D (2011) Autoimmune liver diseases in children – what is different from adulthood? Best Pract Res Clin Gastroenterol 25:783–795CrossRefPubMedGoogle Scholar
  19. Mindikoglu AL, King D, Magder LS, et al (2011) Valproic acid associated acute liver failure in children: case report and analysis of liver transplantation outcomes in the United States. J Pediatr 158:802–807CrossRefPubMedGoogle Scholar
  20. Ng V, Anand R, Martz K et al (2008) Liver retransplantation in children: a SPLIT database analysis of outcome and predictive factors for survival. Am J Transplant 8:386–395CrossRefPubMedGoogle Scholar
  21. Rivera-Penera T, Moreno J, Skaff C et al (1997) Delayed encephalopathy in fulminant hepatic failure in the pediatric population and the role of liver transplantation. J Pediatr Gastroenterol Nutr 24:128–134CrossRefPubMedGoogle Scholar
  22. Romano F, Stroppa P, Bravi M et al (2011) Favorable outcome of primary liver transplantation in children with cirrhosis and hepatocellular carcinoma. Pediatr Transplant 15:573–579PubMedGoogle Scholar
  23. Shiboski CH, Kawada P, Golinveaux M et al (2009) Oral disease burden and utilization of dental care patterns among pediatric solid organ transplant recipients. J Public Health Dent 69:48–55CrossRefPubMedPubMedCentralGoogle Scholar
  24. Shneider BL, Brown MB, Haber B et al (2006) A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000. J Pediatr 148:467–474CrossRefPubMedGoogle Scholar
  25. Siebold L, Dick AA, Thompson R et al (2010) Recurrent low gamma-glutamyltranspeptidase cholestasis following liver transplantation for bile salt export pump (BSEP) disease (posttransplant recurrent BSEP disease). Liver Transpl 16:856–863CrossRefPubMedGoogle Scholar
  26. Sokal EM, Sokol R, Cormier V et al (1999) Liver transplantation in mitochondrial respiratory chain disorders. Eur J Pediatr 158(Suppl 2):S81–S84CrossRefPubMedGoogle Scholar
  27. Sokol RJ, Stall C (1990) Anthropometric evaluation of children with chronic liver disease. Am J Clin Nutr 52:203–208CrossRefPubMedGoogle Scholar
  28. Soltys KA, Mazariegos GV, Squires RH et al (2007) Late graft loss or death in pediatric liver transplantation: an analysis of the SPLIT database. Am J Transplant 7:2165–2171CrossRefPubMedGoogle Scholar
  29. Squires RH, Shneider BL, Bucuvalas J et al (2006) Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr 148:652–658CrossRefPubMedPubMedCentralGoogle Scholar
  30. Squires RH, Ng V, Romero R et al (2014) Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 59:112–131CrossRefPubMedGoogle Scholar
  31. Stevenson T, Millan MT, Wayman K et al (2010) Long-term outcome following pediatric liver transplantation for metabolic disorders. Pediatr Transplant 14:268–275CrossRefPubMedGoogle Scholar
  32. Studies of Pediatric Liver Transplantation Consortium (2007) Annual report 2007. Emmes, RockvilleGoogle Scholar
  33. Varela-Fascinetto G, Castaldo P, Fox IJ et al (1998) Biliary atresia-polysplenia syndrome: surgical and clinical relevance in liver transplantation. Ann Surg 227:583–589CrossRefPubMedPubMedCentralGoogle Scholar
  34. Whitington PF, Balisteri WF (1991) Liver transplantation in pediatrics: indications, contraindications, and pretransplant management. J Pediatr 118:169–177CrossRefPubMedGoogle Scholar
  35. Yu SB, Kim HY, Eo H et al (2006) Clinical characteristics and prognosis of pediatric hepatocellular carcinoma. World J Surg 30:43–50CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.The Hospital for Sick ChildrenTorontoCanada
  2. 2.Division of Pediatric Gastroenterology, Hepatology and Nutrition and SickKids Transplant and Regenerative Medicine Center, The Hospital for Sick ChildrenUniversity of TorontoTorontoCanada

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