Liver failure, or hepatic failure, is a clinical condition that results from significant hepatocyte dysfunction or death. It differs from hepatitis in that patients must have uncorrectable coagulopathy in addition to hepatocyte injury, with or without encephalopathy. Hepatic failure is an acute process and should be differentiated from the acute decompensation of chronic liver disease.

The strict criteria for acute or fulminant liver failure in adults include encephalopathy, coagulopathy, and evidence of hepatic dysfunction without prior evidence of liver disease, occurring within 8 weeks of the first symptoms of illness. Because encephalopathy is uncommon and difficult to identify in infants and young children, most clinicians use uncorrectable coagulopathy and hepatic dysfunction as clinical criteria for liver failure in this age group.

Recognition of hepatic failure and its associated metabolic disturbances (Table 79-1) is crucial so that supportive therapy can be provided until recovery, or liver transplantation. Hepatic failure accounts for up to 15% of pediatric liver transplants in the United States each year.

NEONATES AND INFANTS

Neonates and young infants can present with a range of symptoms, depending on the disease. Some infants are quite ill immediately after birth with coagulopathy and acidosis. This presentation is highly suggestive of hypoxic or ischemic injury, neonatal hemochromatosis, neonatal enteroviral infection, or some other intrauterine or perinatal insult. Laboratory tests may reveal elevated transaminases in the high hundreds to thousands (suggestive of ischemia) and hyperbilirubinemia. Hypoglycemia may also be present. Clinical symptoms suggestive of sepsis, including hypotension and poor perfusion, may occur. Encephalopathy is recognizable in only one-third of these infants.¹ Infants with neonatal hemochromatosis have intrauterine growth retardation, coagulopathy, hypoalbuminemia, ascites, mild transaminase elevation, and varying degrees of renal insufficiency.

CHILDREN AND ADOLESCENTS

Children with acute hepatic failure also may present with a wide variety of symptoms. Those with infectious hepatitis may have fever, malaise, nausea, jaundice, and right upper quadrant pain. They may have been recently discharged from the emergency department or physician’s office with a diagnosis of hepatitis and elevated transaminases, jaundice, and a normal prothrombin time (PT). Many children improve (especially those with hepatitis A), but some return with rapidly worsening jaundice, and signs of coagulopathy such as petechiae, bruising, or bleeding. Mental status changes with encephalopathy may include reversal of the day–night sleep cycle, uncooperative behavior, delirium, stupor, or coma. The physical examination may reveal a shrunken liver.

Patients with hypoxic or drug- or toxin-related injury may present with very high transaminase levels. Metabolic diseases typically present with high transaminase levels and hypoglycemia. Wilson disease presenting as acute hepatic failure is often accompanied by Coombs-negative hemolytic anemia.

It is important to distinguish acute liver failure from acute hepatitis. The former involves an uncorrectable coagulopathy, with or without encephalopathy. The majority of patients who present clinically with hepatitis—elevated alanine transaminase (ALT), with or without jaundice, usually have normal synthetic function (normal PT, albumin)—but this condition can quickly progress to acute liver failure. The causes of acute hepatitis are therefore almost identical to those of acute liver failure. They include infections, metabolic and autoimmune diseases, and toxic injuries (Table 79-2). Infectious hepatitis is most frequently viral, with hepatitis A and Epstein-Barr virus being the most common. In the United States, hepatitis B and C are uncommon causes of acute hepatitis in children.²

In addition to those with acute liver injury, patients with underlying liver disease may present with increasing transaminases, jaundice, and coagulopathy, with or without encephalopathy. This is referred to as an acute decompensation of chronic liver disease. Diseases that involve significant liver fibrosis, such as α₁-antitrypsin deficiency, autoimmune hepatitis, primary sclerosing cholangitis, and Wilson disease, can present in this fashion. These patients need to be evaluated thoroughly, because many have clinical findings that are similar to those in acute liver failure. In addition, many have portal hypertension with thrombocytopenia. These two conditions can contribute to a higher risk of bleeding from esophageal varices, portal hypertensive gastropathy, or mucosal surfaces.