It is the most common cholestatic disorder of childhood and accounts for 50–75 % of pediatric LDLT in most centers [6]. It is characterized by a progressive inflammation of the extrahepatic bile ducts and if left untreated, inevitably leads to cirrhosis and death. A successful hepatic portoenterostomy (Kasai procedure) performed within the first 3 months of life has equivalent survival to liver transplantation performed within the first year [7]. Even then, the child may need a liver transplant at an older age due to increased frequency of cholangitis and failure to thrive. Patients with failed Kasai procedure and those presenting with complications of cirrhosis usually require liver transplantation before 2 years of age.

The hepatic hallmark of this syndrome is the paucity of bile ducts. The cholestasis typically waxes and wanes, and ocular, cardiac, and skeletal manifestations besides hypercholesterolemia may be present. While biliary diversion and medical management may be beneficial in many, liver transplantation can provide a definitive cure in most patients with hepatic effects of this syndrome [8].

This autosomal recessive disease is characterized by increased copper deposition, primarily in the liver and brain. Hepatic manifestations are more common than neurologic symptoms in children. It may present as acute hepatitis or may progress from chronic liver disease to end-stage liver disease. Liver transplant is a curative therapy, indicated for those with severe portal hypertension and those refractory to medical therapy [9].

This autosomal dominant deficiency in serum α1-antitrypsin is the most common genetic liver disease in children of Northern European descent and the most common metabolic cause of neonatal hepatitis. Children with end-stage liver disease benefit from liver transplantation.

Deficiency of liver enzymes involved in metabolizing ammonia to urea results in hyperammonemia and neurologic sequelae. Liver transplantation before the onset of irreversible brain damage can be curative in these children.

It is predominantly caused by infections such as viral (enterovirus; herpes simplex virus; hepatitis A, B, C; cytomegalovirus, Epstein-Barr virus, rubella, etc.), bacterial (Streptococcus pyogenes, Staphylococcus aureus, tuberculosis, syphilis), toxoplasmosis, etc., although a significant proportion are of idiopathic origin. Other causes include inborn errors of metabolism, mitochondrial defects, adrenal insufficiency, Budd-Chiari syndrome, polycystic disease, etc.

Children of any age can be affected by acute liver failure. Other than the causes enumerated above for neonatal hepatitis, other causes like idiosyncratic or dose-related drug toxicity and autoimmune disease can also cause fulminant hepatitis necessitating liver transplantation.

Hepatoblastoma is the most common primary liver tumor in children. The majority of hepatoblastomas can be managed by liver resection and is preceded by chemotherapy if required. However, liver transplantation may be indicated for unresectable intrahepatic tumors. They comprise less than 3 % of pediatric LDLT. Other uncommon tumors like HCC with advanced cirrhosis, and benign tumors like adenoma or arteriovenous malformations replacing nearly all liver tissue, are also indications for liver transplantation.

A potential recipient benefits from early referral to a transplant center for simultaneous evaluation and preoperative management by an experienced multidisciplinary team. The diagnosis, severity of disease, and need for liver transplant can be validated, and the evaluation protocol is initiated. The child is put on the waiting list for DDLT according to the regional guidelines. Management based on severity of liver disease, for the specific etiology, and for various complications can be started.

Close consultation among the transplant surgical team, pediatrician, hepatologist, anesthesiologist, radiologist, psychiatrist, nutritionist, social worker, and nursing team is essential. Depending upon coexisting morbidities, consultations from other specialties such as pulmonology, cardiology, nephrology, neurology, hematology, etc., may be required.

A thorough physical examination and investigations are carried out (Table 27.2).

Patients who are medically stable can be investigated on an outpatient basis, whereas those candidates with acute liver failure may need to be managed in an ICU setting. The PELD score was developed to assess the risk of mortality in children with chronic liver disease [10]. It is based on the principle that severity of liver disease is more when multiple hepatic functions such as protein synthesis, bile excretion, and metabolic and immunologic functions are compromised. The urgency for transplantation can thus be assessed using a formula based on the measurement of serum albumin, bilirubin, INR, and growth retardation.

Fulminant liver failure (FHF) in children differs from that in adults in its etiology and time to progression. Some cases may resolve without transplantation, and the outcomes of transplantation for FHF are inferior to transplantation for chronic liver disease. Hence, the decision to proceed with LDLT is a difficult one. Prognostic scoring models like the King’s College criteria [11], which is based on age, etiology, duration of jaundice, INR, and bilirubin, and the Clichy criteria (based on age and factor V levels) have been developed, but their positive predictive value for pediatric acute liver failure is low, which can possibly lead to higher transplantation rates [12].

At this stage of the evaluation, any possible contraindications for transplant are assessed. There are relatively few absolute contraindications to pediatric LDLT, such as uncontrolled sepsis or presence of extrahepatic malignancy. Massive brain injury or uncontrolled cerebral edema in metabolic diseases or fulminant liver failure, or progressive extrahepatic disease such as severe pulmonary hypertension with hypoxemia, also precludes liver transplantation. Technical factors such as associated anomalies or extensive portal thrombosis, presence of HIV infection, and developing multiorgan failure may be considered as relative contraindications for transplant.

It is vital that an excellent rapport is created between the child’s family and the medical staff managing the patient. A long stay in the hospital involving complex treatment procedures and risk of numerous complications can strain relationships easily. The social worker can help identify logistic and financial issues besides social dynamics which can impact the management of the patient. At the same time, a psychosocial evaluation of the older child and making him aware about the illness and its management in an optimistic manner can be helpful.

The elective nature of LDLT permits optimization of the child’s status before transplantation. A child with chronic liver disease may be mostly managed in an outpatient setting, while a child with acute liver failure may need aggressive treatment in an ICU.

Vaccination is more effective if given before transplantation and initiation of immunosuppression regimens [13]. An accelerated regimen of routine vaccines may be required considering the young age of many recipients. Achieving high levels of antibody to HBsAg by vaccination can help prevent de novo HBV infection after transplant [14].

Malnutrition is common with pediatric liver disease, and growth failure is one of the indications for transplantation. It is caused by multiple factors like increased catabolism, anorexia due to liver disease, and abdominal heaviness due to hepatosplenomegaly, malabsorption, cholestasis, and impaired parenchymal function. Preoperative malnutrition and sarcopenia can have significant negative impact on liver transplantation outcomes [15]. Anthropometric assessment and delayed milestones of development can guide nutritional therapy. Vitamin and medium-chain triglyceride supplements in normal diet, high-caloric-density preparations, nasogastric feeding, and parenteral nutrition may be required. Growth failure due to parenchymal disease cannot be corrected after a point by nutritional therapy, and hence, it is a strong independent indication for liver transplantation.

Coagulopathy in decompensated chronic liver disease or in acute liver failure is indicative of worsening condition. Management of coagulopathy before transplant can greatly improve surgical outcomes. It can also increase safety of invasive procedures such as liver biopsy or invasive intracranial pressure monitoring. Increased bleeding tendency in liver disease results from a decrease in both procoagulant and anticoagulant factors as well as due to factors like altered platelet activation, hemodynamic alterations of portal hypertension, endothelial dysfunction, sepsis, and renal failure. Correction of coagulopathy must hence focus on all these factors rather than simple replacement of depleted coagulation factors [16]. Hospital guidelines regarding transfusion of fresh frozen plasma, cryoprecipitate, platelets, recombinant factor VIIa, and plasmapheresis should be prepared, as the benefit of these measures is not broadly accepted.

Neonatal candidates for transplantation usually have acute liver failure, and pulmonary, renal, and cardiac dysfunction is common. Their small size makes management difficult, as interventional procedures such as hemofiltration are not easy to perform. They require hyperreduced size grafts, increasing the risk of surgical complications.

Survival outcomes of LDLT recipients weighing less than 10 kg are inferior to those with higher weights, and hence ideally LDLT should be done after the age of the child is at least 6 months old [17]. However, as liver failure results in growth retardation, LDLT may be required in children with low weights, if they are below the third percentile of the growth curve or if the severity of the liver disease so demands; hyperreduced size grafts are required in such cases.

Donor evaluation is similar to that for LDLT in adults. Guidelines regarding degree of donor relationship and donor age are usually framed by the local health authority. For example, the Organ Transplant Act of Taiwan permits only adult relatives within fifth degree of consanguinity to be donors, whereas there is no provision for emotionally related donors. Donation should be voluntary, and the willingness of the donor should be thoroughly assessed in one-on-one psychosocial consultations. The donor should have an understanding of the potential risks associated with the surgery, especially as the donor may be an important caregiver for the recipient. Presence of social and family support systems for the donor and their comfort with the donor’s decision should be assessed. Thus, a structured assessment and informed consent are of vital importance in donor surgery.

If there are multiple potential donors, then a basic screening is conducted to rule out contraindications for donation. Presence of active infection, malignancy, and systemic disease are obvious contraindications, whereas history of past infection or malignancy needs further assessment. Seropositivity for HBV, HCV, or HIV generally precludes organ donation, while LDLT with HBcAb-positive grafts may be done with pretransplant hepatitis B vaccination and if required, posttransplant antiviral agents [18].

ABO incompatibility is a major factor limiting the donor pool in LDLT. ABO-incompatible LDLT and DDLT have resulted in high rates of intrahepatic nonanastomotic biliary strictures, liver necrosis, and lower graft survival before the introduction of rituximab. On the other hand, outcomes of ABO-incompatible LDLT for recipients aged less than 1 year are similar to those of ABO-compatible LDLT, probably because the immune system is still developing [19]. In order to reduce the incidence and severity of reactions due to blood group incompatibility, various modalities like plasmapheresis to reduce blood group antibodies in serum, rituximab to reduce B cells via cytotoxic reaction, and local graft infusions of prostaglandins and steroids have been used. The outcomes for ABO-incompatible LDLT for older children are expected to improve as the immunosuppression protocols for ABO-incompatible LDLT in adults are being improved [20].

When inborn errors of metabolism are the indication for pediatric LDLT, there is a risk that the related donor may be affected by the same disease. Symptomatic donors are usually excluded during the evaluation process, but grafts from asymptomatic donors have been utilized without incident [21]. Many of these metabolic disorders are inherited in an autosomal recessive manner, and hence, the recipient has homozygous affected genes, while the asymptomatic donor may have two normal genes or carry one affected gene. Alternative methods for investigating the donor for inheritable metabolic diseases include carrying out a metabolic loading test or taking a liver biopsy from the donor to accurately measure the target enzyme activity. Such methods may be particularly useful for ornithine transcarbamylase deficiency, an X-linked recessive inherited urea cycle defect, as even heterozygous female donors who carry the recessive gene may become symptomatic due to mosaicism [22].

Complete HLA matching is not a criteria for donor selection in liver transplants because of the tolerogenic nature of the liver and the paucity of donors, although it can lead to low rates of acute rejection and increased chances of developing operational tolerance after transplant (absence of graft rejection despite withdrawal of immunosuppression) [23]. Conventionally, the cytotoxic lymphocyte crossmatch between donor lymphocytes and recipient sera is performed to assess risk of graft rejection, although quantitative assays of donor-specific antibodies and DNA-based typing methods may be more accurate and efficient.

Normally, the main concern in liver transplantation is to avoid graft rejection (initiated when the recipient’s immune system identifies graft antigens as foreign and initiates an immune response) rather than GVHD (graft versus host disease, where the lymphocytes in the graft recognize the recipient cells as foreign and initiate an immune response even though the recipient immune system is quiescent).

However, when a parent is the donor for a pediatric LDLT, the risk of GVHD has to be assessed. If the parent is homozygous for HLA allotypes and the child is heterozygous, then the recipient immune system tolerates the graft, but the graft lymphocytes may initiate a GVHD against the recipient’s HLA allotypes. In such cases, an alternative donor may be needed. Preoperative identification of anti-HLA antibodies quantitatively and qualitatively may help in avoiding severe immune intolerance (e.g., by initiating immunosuppression regimens in the recipient similar to those for ABO incompatibility) and expand the donor pool [24].

Radiology and volumetry: The left lobe or left lateral segment is almost invariably used in pediatric LDLT. Numerous variations of size, shape, and anatomy can be encountered in both the donor and recipient in pediatric LDLT, and hence, good preoperative imaging is invaluable in preparing for the procedure. A left lobe graft leaves a safe remnant liver volume of more than 40 % of the standard liver volume in the donor. A graft-to-recipient weight ratio (GRWR) of 1–3 is ideal for pediatric recipients. Grafts may turn out to be small for size when a diminutive-sized donor is present for an adolescent or due to iatrogenic ischemia of a segment from a left or left lateral graft or due to portal hyperperfusion in advanced cirrhosis. More frequently in pediatric LDLT, there is the risk of having a large-for-size graft, if the donor is big or the child is too small. A GRWR greater than 5 predisposes to portal hypoperfusion, followed by graft ischemia and graft dysfunction. It is relatively straightforward to estimate the volume of a left lobe graft by CT volumetry. Estimation of the volume of a left lateral graft and a monosegment graft is more difficult and requires expert review. A fatty liver more than 30 % may not be preferred in most centers. It is also useful to estimate the volume of the spleen in the recipient, as the relative volumes of the liver and the spleen give an estimate of the portal hyperperfusion [25].

Apart from the graft volume, the dimensions of the graft and the abdominal cavity are also important. The anteroposterior diameter of the graft (the maximum distance between the anterior surface of the graft and the porta hepatis on CT imaging of the donor) should be accommodated inside the child’s abdominal cavity (the distance from the vertebral body to the anterior abdominal wall on CT imaging of the recipient). A recipient with preoperative ascites or hepatomegaly may be able to receive a larger graft. While a difference of 2 cm between the graft size and the size of the abdominal cavity may be overcome due to the compliance of the pediatric chest wall and abdomen, any excessive disparity may require temporary abdominal wall closure using a prosthetic material, with its attendant risks [26].

Portal vein hypoplasia is common in patients with biliary atresia and so the portal vein size, portal flow velocity, and location of the splenomesenteric junction in relation to the pancreas and coronary vein should be assessed preoperatively. The coronary vein may be needed as a portal vein replacement or it may need to be ligated to increase portal perfusion. Early branching of P2 and P3 from the main portal vein, replacing the left portal vein is possible in the donor and should be looked for.

CT angiography of the donor liver gives important information about the arterial anatomy of the left side. An accessory hepatic artery or replaced left hepatic artery may arise from the left gastric artery and run through the lesser omentum. Unless it is extremely small, it is not sacrificed, but taken along with the graft. Adequate length of the hepatic artery may be obtained by dividing the left gastric artery proximally. The A4 may arise from the common, left or right hepatic artery and has to be carefully dissected for left lobe LDLT. The CT angiography gives information about the size of the hepatic arteries (which may be large in cases of biliary atresia with portal hypoplasia) and patency of the gastroduodenal and gastroepiploic artery (which is the nearest alternative inflow artery of suitable size and length if the recipient hepatic arteries cannot be used). The biliary anatomy is evaluated in the donor by MRCP or three-dimensional reconstruction of high-resolution CT images. The left-sided graft more commonly has only a single bile duct.

A wide venous outflow reconstruction is crucial for obtaining good outcomes after LDLT. The middle hepatic vein (MHV) is usually taken along with the left lobe graft, and the middle and left hepatic veins usually form a single outflow tract. Occasionally, V2 and V3 may drain separately into the MHV instead of forming the LHV. When a hyperreduced size graft is required, preoperative imaging can guide the surgical technique, by delineating the vascular anatomy and estimating the volumes and dimensions of segments 2 and 3. Close coordination between the surgical teams operating on the donor and recipient ensures that no time is wasted and minimal graft ischemic times are achieved.

The left lobe hepatectomy for pediatric LDLT is similar to the adult donor hepatectomy. The common trunk of the MHV and LHV is exposed by suprahepatic dissection after dividing the falciform ligament. The left inferior phrenic vein is divided early in the dissection to prevent inadvertent bleeding. The gastrohepatic ligament is incised, taking care to preserve any accessory hepatic vessels running in the ligament. The Arantius duct is carefully transfixed where it enters the LHV and divided. This maneuver enables the common trunk of the MHV and LHV to be safely looped.

The gall bladder is mobilized away from its liver bed, and the cystic plate is separated from the hilar plate. Intraoperative cholangiography (IOC) is performed in left-sided grafts if there is history of previous biliary surgery in the donor or if the preoperative MRCP shows variations such as the right posterior sectoral duct arising from the left hepatic duct, trifurcation of the hepatic ducts, or branching of the left hepatic ducts within 1 cm of the confluence [27]. IOC is performed using an olive-tipped needle inserted into the infundibulum or the cystic duct. The gall bladder acts as a guide to the biliary and arterial anatomy of the hilum and is useful for retraction. Hilar dissection is started with the aim of exposing the left hepatic artery first. The A4 is identified if present. The left portal vein is looped after identifying and dividing its caudate branch(es). The arterial and portal inflow to the left lobe is temporarily occluded, and the left lobe demarcation is marked on the surface of the liver. The volume of the graft is estimated again by visual inspection.