Acute liver failure is defined as a liver disease that produces hepatic encephalopathy within 6 months of the initial diagnosis. The condition is known as fulminant liver failure when the encephalopathy develops within 2 weeks of the onset of jaundice, and as subfulminant liver failure when the encephalopathy develops within 3 months. In the United States, accidental or deliberate ingestion of acetaminophen accounts for almost 50% of cases of acute liver failure, while autoimmune hepatitis, other drugs and toxins, and acute hepatitis A and B infections account for the remainder of cases. In Asia, acute hepatitis B and E predominate as causes of acute liver failure.
MORPHOLOGYTheclinicalsyndromeofacuteliverfailureisreflectedanatomicallyandhistologicallyasmassive hepatic necrosis. Theliverissmallandshrunkenduetolossofparenchyma(
Fig.16.4A ).Microscopically,therearelargezonesofdestructionsurroundingoccasionalislandsofregeneratinghepatocytes(
Fig.16.4B ).Scarismostlyabsentgiventheacutenatureoftheprocess.
Acute liver failure manifests with nausea, vomiting, jaundice, and fatigue, which are followed by the onset of life-threatening encephalopathy, coagulation defects, and portal hypertension associated with ascites. Typically, transaminase levels in the serum are elevated into the thousands. The liver is initially enlarged by swelling and edema related to inflammation, but then as parenchyma is destroyed the liver shrinks dramatically. Eventually, as hepatocytes are lost, serum transaminase values level off and then decline rapidly as their source disappears. Worsening jaundice, coagulopathy, and encephalopathy develop; with unabated progression, the end result is multiorgan failure and, without transplantation, death. Manifestations of acute liver failure include the following: • Jaundice and icterus (yellow discoloration of the skin and sclera, respectively) due to retention of bilirubin, and cholestasis due to systemic retention of not only bilirubin but also other solutes eliminated in bile.
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Fig. 16.4 Massivelivernecrosis.(A)Theliverissmall(700g),bile-stained,soft,andcongested.(B)Hepatocellularnecrosiscausedbyacetaminophenoverdose.Confluentnecrosisisseenintheperivenularregion(zone3,arrow).Thereislittleinflammation.Residualnormaltissueisindicatedbytheasterisk. (Courtesy of Dr. Matthew Yeh,University of Washington,Seattle,Washington).
Hepatic encephalopathy encompasses a spectrum of disturbances in consciousness ranging from subtle behavioral abnormalities, to confusion and stupor, to coma and death. Encephalopathy may develop over days, weeks, or a few months after acute injury. Fluctuating neurologic signs, including rigidity, hyperreflexia, and asterixis, may develop. Asterixis refers to a nonrhythmic rapid extension-flexion movement of the head and extremities, best seen as “flapping” of the hands when the arms are held in extension with dorsiflexed wrists. Elevated ammonia levels in blood and the central nervous system correlate with impaired neuronal function and brain edema.
Coagulopathy. The liver is the source of a number of coagulation factors that decline in the face of liver failure, leading to easy bruising and bleeding. Paradoxically, disseminated intravascular coagulation (Chapter 12) also may occur due to failure of the damaged liver to remove activated coagulation factors.