Auxiliary Liver Transplantation for Acute Liver Failure in Children

Introduction

Acute liver failure (ALF) is defined as the acute onset of severe hepatitis with loss of hepatic function in patients with no known underlying liver disease. ALF can result from various hepatic insults including viral infections, drug-induced liver injury, toxin exposures, and autoimmune diseases ( Fig. 37.1 ). Non-A, non-B hepatitis, an unexplained cause for ALF, remains the most common scenario.

ALF in children is a life-threatening event with a mortality rate as high as 90% in the absence of liver transplantation (LT), particularly for those with severe hepatic encephalopathy. It is relatively rare and accounts for approximately 10% to 15% of all LTs in children. The incidence varies by age: 6.9% for 0 to 2 years and 17.9% for 3 to 10 years, with the greatest burden coming in the 11-18-year age group (18.7%). With current intensive medical management and LT for patients meeting established transplant criteria, survival rates have improved to greater than 85% at 1 year and beyond.

In 1974, Karvountzis et al. showed that if patients survive the initial phase of ALF, native liver (NL) function could recover without long-term sequelae. However, for those patients who do not recover hepatic function, orthotopic LT (OLT) became the treatment of choice.

Although general clinical indicators help stratify which patients face the highest mortality risk without transplantation and also those who are likely to recover with supportive care only, there are not yet sufficiently accurate predictors in pediatric ALF to determine who will survive in the absence of transplantation. As such, there is a significant subset of children who have the potential for spontaneous recovery of liver function yet who still undergo standard OLT. The risks of OLT followed by a lifetime on immunosuppressants (IS) are a significant and unnecessary burden.

Current Guide to Listing Criteria for Liver Transplant in Acute Liver Failure in Children

In pediatric patients with ALF, listing criteria focus on acute metabolic and synthetic liver dysfunction, including the following indications, presented in Table 37.1 .

Liver Regeneration

Outcomes of LT for ALF have improved over the past 30 years but are still worse than those for chronic liver disease (CLD) because the children are sicker and invariably transplanted from an intensive care setting. Following liver replacement, these children will have to remain on lifelong immunosuppression with its associated risks of malignancy, renal impairment, hypertension, and infection. The likelihood of liver regeneration in ALF depends on the etiology of liver failure, whether there is a persistent insult, as in patients with sub-ALF, or a single insult, as in mushroom poisoning or acetaminophen overdose; hyper-ALF patients are more likely to regenerate than subacute; age when children (and adults < 40 years of age) are more likely to regenerate compared with adults; and pattern of hepatocyte loss, where there is a complete loss of the hepatocyte population regeneration is unlikely. The best treatment option for ALF is to temporarily support liver function until the NL has sufficiently regenerated. Unlike acute kidney injury where hemodialysis can completely replace renal function until the kidneys recover, there are no effective artificial means available for replacing liver function. Although existing liver support devices can carry out some functions like detoxification, none can cover the numerous functions of the liver long enough for the liver regeneration to occur predictably. These devices could serve as a bridge to LT, providing some stability while awaiting emergency LT. Auxiliary LT (ALT) is the only treatment option available at present that can act as a reliable bridge to liver regeneration so that patients are spared lifelong immunosuppression.

Auxiliary Partial Orthotopic Liver Transplant

Auxiliary partial orthotopic liver transplant (APOLT) was proposed as an alternative surgical approach to treat ALF and to allow recovery of NL function. APOLT is a unique surgical procedure in which a portion of the native damaged liver is removed (usually left lobectomy in children), and a partial or whole liver graft is implanted and used as a bridge to NL recovery. The goal of the procedure is to provide support for the liver function of these children while allowing NL to recover.

When the recovery is achieved, immunosuppression is weaned, causing the transplanted liver to involute. This procedure is most beneficial in children and young adults because of the potential to avoid lifelong immunosuppression and its side effects. However, the transplant criteria remain the same for the full liver replacement and ALT. A key consideration is that early patient survival should be the same for both procedures. Our experience suggests that long-term survival seems to be better for the APOLT group than for whole liver replacement group.

Initially considered technically challenging, APOLT has become refined as a surgical procedure, and outcomes are good for selected indications and should be considered to be the gold standard of care for children with ALF.