Survival and Quality of Life in Children

Cholestatic Liver Disease

Secondary biliary cirrhosis resulting from extrahepatic biliary atresia is the most common indication for liver transplantation in children, with metabolic disorders being a distant second. However, underlying liver disease has little if any effect on patient and graft survival. Children with biliary atresia once had the poorest results but now enjoy survival rates that do not differ statistically from children with metabolic disorders, as shown in Table 101-4 . Morbidity in children with biliary atresia is significant, but it is similar to that of children who have undergone transplantation for other indications. This morbidity is caused by the young age of these patients, many of whom have been subjected to several operations before transplantation. As initial treatment, portoenterostomy is indicated in patients with biliary atresia because it may provide some temporary relief from the detrimental consequences of the disease, allowing them to grow and become better surgical candidates for liver transplantation should they need it later on in life.

In a recent publication 134 children with biliary atresia who underwent liver transplantation were retrospectively grouped in three categories: no portoenterostomy (22 cases), portoenterostomy with early liver failure (63 cases), and portoenterostomy with late liver failure (49 cases). Early failure was defined as those patients who developed organ failure within 12 months of the portoenterostomy and late liver failure as those patients who developed organ failure after 12 months from the portoenterostomy. The group with early liver failure after portoenterostomy had worse outcomes than the other two groups, indicating that the portoenterostomy was not responsible for the increased morbidity and mortality, but that there were possibly other compounding factors, not yet characterized.

The polysplenia syndrome is a variant of biliary atresia associated with multiple spleens, preduodenal portal vein, intestinal malrotation, and absence of the vena cava. There are also variations within this syndrome. Affected children appear to have a high complication rate after liver transplantation. The hepatectomy is usually easier, because the vena cava is absent, but the reconstruction of the preduodenal vein may pose a technical challenge. Some of these patients also have situs inversus. In our experience and that of others, segmental transplants from deceased or living donors is an excellent solution to the spatial problems associated with situs inversus.

Patients with Alagille syndrome are also reported to have a poorer rate of survival because of their propensity for severe peripheral pulmonic stenosis and associated pulmonary hypertension. However, awareness of this complication and proper perioperative management can ensure a successful outcome.

Metabolic Disorders

Hepatic replacement is a good therapeutic option for children with certain metabolic disorders based in the liver. These metabolic disorders fall into two categories: first, those associated with liver injury resulting in acute or chronic liver failure and second, those diseases not associated with intrinsic liver disease but a metabolic defect that results in injury of other organs. A significant phenomenon is the recipient’s conversion to the donor phenotype after undergoing transplantation for an inborn error of metabolism based in the liver (e.g., tyrosinemia, α ₁ -antitrypsin deficiency, and type 1 hyperoxaluria, among others); this represents an actual correction of the metabolic defect.

The timing of transplantation is critical to ensure good outcomes. This is particularly important in patients with methylmalonicacidemia, where the risk for brain injury and permanent sequela is high during episodes of hyperammonemia. In a recent report, liver transplantation or combined liver/kidney transplantation for methylmalonicacidemia eradicated episodes of hyperammonemia, resulting in excellent long-term survival and stabilization of psychomotor development. Long-term follow-up is under way to evaluate whether patients who undergo early liver transplantation need kidney transplants later in life. Excellent outcomes with liver transplantation have also been observed in the management of urea cycle disorders in children. There are six urea cycle disorders, which include N -acetyl glutamate synthetase deficiency, carbamoyl phosphate synthetase I (CPSI) deficiency, ornithine transcarbamylase (OTC) deficiency, argininosuccinate synthase deficiency (also known as classic citrullinemia ), and argininosuccinate lyase deficiency, and arginase deficiency. In a recent report of 23 children who underwent liver transplantation for these disorders, the long-term patient and graft survival were 100% and 95%, respectively. There were no episodes of hyperammonemia or metabolic crises in any patients after transplantation on protein-unrestricted diets. One of the CPSI and four of the OTC deficiency still do require citrulline supplementation. Living donor liver transplantation has been used effectively for the treatment of several metabolic disorders based in the liver.