Overall Bottom Line

There are key differences between adult and pediatric LT with respect to indications, evaluation of candidates, timing and priority for transplant, and management.
Biliary atresia is the most common indication for LT in children in comparison with hepatitis C-related cirrhosis in adults.
The PELD score is used to prioritize organ allocation in children <12 years, while the MELD score is used for those >12 years, similar to adults.
Growth and development as well as psychosocial aspects require special attention in children requiring LT.
Exposure to EBV for the first time after LT poses unique challenges in pediatrics.

Section 1: Background

LT in children has become the standard of care for children with acute liver failure and ESLD since the early 1980s

History

1963 – First LT in a child with biliary atresia by Thomas Starzl.
1978 – Cyclosporin used as an immunosuppressant.
1989 – Tacrolimus introduced (primary immunosuppression in USA today).
1991 – First living donor transplantation was performed in a child as there was an organ shortage crisis particularly in small children.
2002 – PELD and MELD scores introduced to prioritize patients waiting for LT in the USA.

The major issue in transplantation today is the organ shortage, causing longer waiting times and increasing waiting list mortality.
To overcome this, various strategies including live donor transplantation, split LT, extended criteria donors such as elderly donors, hepatitis B core antibody positive donors, and donation after cardiac death have been employed.
Due to poorer outcome after transplant, we typically avoid using extended criteria donors and donation after cardiac death unless the benefit outweighs the risks in pediatric LT.

Incidence/prevalence

Around 12 000 pediatric LTs have been performed in the USA.
Approximately 600 transplants are performed annually.
Initial survival rates 40 years ago were in the 30% range, but now 1-year survival rates are as high as 90%.

Economic impact

LT is one of the most expensive medical and surgical procedures performed in the world today.
Conservative estimates of the cost of a single uncomplicated LT in the USA are several hundred thousand dollars.
The direct and indirect costs associated with liver disease and associated treatment exceeds $180 billion annually in the USA.
It is generally believed that when compared with other accepted medical technologies, LT meets the cost-effectiveness criterion of having an additional benefit worth the added cost.

Indications for LT in children

Cholestatic liver disease:
- Extrahepatic biliary atresia.
- Alagille syndrome.
- Sclerosing cholangitis.
- Progressive familial intra-hepatic cholestasis.
- Idiopathic neonatal hepatitis.
Fulminant liver failure.
Metabolic liver disease:
- Structural damage to the liver: Wilson disease, alpha-1 antitrypsin deficiency, tyrosinemia, cystic fibrosis, glycogen storage disease.
- No structural damage to the liver: Urea cycle defects, primary hyperoxaluria.
Autoimmune hepatitis.
Liver tumors:
- Infantile hepatic hemangioendothelioma.
- Hepatoblastoma.
Miscellaneous:
- Cryptogenic cirrhosis.
- Congenital hepatic fibrosis.
- Drug overdose/toxicity.
- Viral hepatitis.
- Retransplantation secondary to complications of first transplant.

Contraindications to LT in pediatrics

Coma with irreversible brain injury.
Uncontrolled systemic infection including AIDS.
Liver tumors with extrahepatic metastasis.
Terminal progressive systemic disease.
Inadequate cardiac or pulmonary function.

Timing of LT

Early referral is key to a successful LT
In acute liver failure
- INR >2 despite parenteral Vitamin K supplementation.
- INR >1.5 and encephalopathy.
In biliary atresia:
- Persistence of cholestasis 6–8 weeks after Kasai portoenterostomy.
- Failure to thrive, weight and height < third centile.
- Recurrent cholangitis.
- Portal hypertension complications – ascites, GI bleeding.
- Poor synthetic function with prolonged INR, reduced albumin.
In metabolic disorders:
- Failure of medical therapy.
- Repeated metabolic decompensations increase the risk of neurological deficits.

Evaluation for LT

Initial consultation by pediatric hepatologist:
- To confirm diagnosis and establish need for LT.
- To discuss other therapeutic options versus LT.
- To explain sequence of events involved in LT evaluation, listing, surgery and subsequent course and introduce to LT surgeon and coordinator.
- To begin to establish relationship with family and answer any concerns before initiating formal evaluation by the rest of the team.
Evaluation by the transplant surgeon:
- To assess suitability for LT and assess need for specialized imaging.
- To discuss type of organ, deceased versus living donor, scoring system and waiting list.
- To explain technical aspects of surgery including complications.
- To discuss outcomes after LT and side effects of immunosuppression.
Evaluation by nutritionist:
- To assess recipient’s nutritional status and caloric intake.
- To initiate tube feeding in conjunction with the hepatologist if failure to thrive.
Evaluation by infectious disease specialist:
- To ensure there are no infection issues that preclude LT.
- To ensure immunization schedule is expedited especially live vaccines in infants and babies.
Evaluation by cardiologist:
- To ensure that the child has stable cardiac status and can undergo transplant surgery.
Evaluation by social worker:
- To ensure that the child comes from a stable home and is able to comply with the post-transplant regimen and provide support as required.
Evaluation by transplant coordinator:
- To coordinate the child’s evaluation for LT.
- To go over the LT process including scoring, donor types and outcomes and take informed consent for evaluation and listing.
- To provide education about the transplant process and give appropriate manuals.
- To organize listing of the patient after evaluation is completed.
- To provide liaison between physicians, the family and the referring doctor.
Repeat consult by the hepatologist at the end of evaluation:
- To reinforce the information given by other members of the team.
- To ensure that the family understands implications of being listed for LT.
- To answer any concerns and repeat information as required.
- To ensure there is an interim plan for management until LT.