Acute Liver Failure and Liver Transplantation

Pierre Tissieres

Denis J. Devictor

KEY POINTS

Infants and children with acute liver failure (ALF) should be referred to centers with expertise in pediatric liver disease, as determination of an accurate etiologic diagnosis before encephalopathy occurs is critical.

Liver support devices may stabilize hemodynamics, improve neurologic status, and give additional time for emergency liver transplantation (LT).

Encephalopathy and coagulation parameter (factor V activity, prothrombin time, and international normalized ratio) kinetics are major ALF severity criteria that aid in deciding whether to perform emergency LT.

Care following LT requires a complete understanding of the surgical and medical specificities of hepatic diseases and the management of postoperative complex multiorgan failure.

LT has drastically changed prognosis of pediatric ALF and end-stage liver disease.

ACUTE LIVER FAILURE

Acute liver failure (ALF) is a rare disease in most countries but remains endemic in some regions where viral hepatitis is highly prevalent. In the United States, the estimated frequency of ALF is 17 cases per 100,000 per year, inclusive of all age groups. The incidence of ALF in the pediatric population is unknown but accounts for 10%-15% of all pediatric liver transplantations (LTs) (1,2). In neonates and infants, metabolic diseases are the main cause of ALF and many are amenable to medical therapies, which may preclude the need for LT (3,4). In older children, viruses (especially hepatitis A virus), drug-induced hepatotoxicity, and autoimmune hepatitis are the most common identified causes of ALF. The cause of ALF remains undetermined in a large proportion of children (3,5,6). Consensus recommendations regarding management of ALF in adults have been published but these remain scarce for children (7,8,9,10). This chapter examines the specificities of ALF in neonates and children with emphasis on definition, emerging causes, clinical presentation, and controversies in management. Available medical therapies for metabolic diseases presenting with ALF in infancy are also discussed.

Definition and Classification of ALF

ALF was originally described, by Trey and Davidson in 1970, as a severe liver injury in a patient with no previous history of liver disease, which progressed to hepatic encephalopathy (HE) within 8 weeks of the initial symptoms (usually onset of jaundice). This definition was inadequate for infants and children who may present with ALF from an asymptomatic metabolic disease with encephalopathy unrelated to ALF or who may not develop encephalopathy in the course of ALF despite an unfavorable outcome. ALF in children is defined as a multisystemic disorder involving severe impairment of liver function, with or without encephalopathy, in the absence of underlying liver disease. Since 1999, the pediatric acute liver failure (PALF) study group, a consortium of 24 active pediatric hepatology centers, created a database of children with ALF (6). Their criteria for pediatric ALF includes patients from birth through 18 years who meet the following criteria: (a) no evidence of chronic liver disease, (b) biochemical evidence of acute liver injury, and (c) hepatic-based coagulopathy defined as a prothrombin time (PT) ≥15 seconds or an international normalized ratio (INR) ≥1.5 not corrected by vitamin K and the presence of HE, or PT ≥20 seconds or INR ≥2.0 regardless of the presence or absence of clinical HE. In some countries, coagulation factor V <50% is part of the definition of hepatic-based coagulopathy.

Causes of ALF

ALF can be schematically classified into seven categories: metabolic, infective, toxic, autoimmune, malignancy-induced, vascular-induced, or undetermined (18%-47% of cases) (2,3,10,11,12,13,14,15,16,17) (Table 103.1). The relationships between these etiologies are highly age-dependent. Early identification of the cause of ALF is of paramount importance for several reasons. In some cases, ALF may be reversed with immediate initiation of specific therapies. This is principally the case in certain metabolic diseases (galactosemia, fructosemia, and hereditary tyrosinemia type 1 [HT-1]), Wilson disease, autoimmune hepatitis, or acetaminophen-induced ALF (4

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