Pediatric metabolic liver diseases: Evolving role of liver transplantation

Abstract

Metabolic liver diseases (MLD) are the second most common indication for liver transplantation (LT) in children. This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation. LT is also performed in metabolic disorders for end-stage liver disease, its sequelae including hepatocellular cancer. It is also performed for preventing metabolic crisis’, arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia. Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis, cholestasis, inflammation, variable amount of fibrosis, and cirrhosis. The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT. A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters. Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver. The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.

Keywords: Liver transplantation; Metabolic liver disease; Tyrosinemia; Wilson disease; Glycogen storage diseases; Urea cycle disorders; Pathology; Auxiliary liver transplant

Core Tip: Metabolic disorders are important cause of morbidity and mortality in children. Their clinical presentations are varied and include end-stage liver disease, hepatocellular cancer, renal tubular acidosis, seizures, encephalopathy, myopathy etc. Liver transplantation (LT) is a curative option in many metabolic disorders. LT is contraindicated in mitochondrial disorders with significant extrahepatic involvement. A combined liver kidney transplant is needed in disorders where the underlying defects significantly damages both the organs. The outcome of LT is excellent in metabolic disorders. Auxiliary partial orthotopic LT is an attractive option as it provides the defective enzymes keeping the native liver intact and may hold an option of withdrawing immunosuppression in case gene therapy can be offered in future.