Portosystemic Encephalopathy

Portosystemic encephalopathy may occur in fulminant hepatitis caused by viruses, medications, or toxins, but it more commonly occurs in cirrhosis or other chronic disorders when extensive portosystemic collaterals have developed as a result of portal hypertension. Encephalopathy may also follow portosystemic anastomoses, such as surgically created anastomoses connecting the portal vein and vena cava (portacaval shunts, transjugular intrahepatic portosystemic shunting [TIPS]).

In portosystemic shunting, absorbed products that would otherwise be detoxified by the liver enter the systemic circulation directly and cause toxicity to the brain, particularly to the cerebral cortex. The substances causing brain toxicity are not precisely known. Ammonia, a product of protein digestion, is an important cause, but other factors (eg, alterations in cerebral benzodiazepine receptors and neurotransmission by gamma–aminobutyric acid [GABA]) may also contribute. Aromatic amino acid levels in serum are usually high and branched-chain levels are low, but these levels probably do not cause encephalopathy.

Symptoms and signs of encephalopathy tend to develop in progressive stages (see table Clinical Stages of Portosystemic Encephalopathy).

Symptoms usually do not become apparent until brain function is moderately impaired. Constructional apraxia, in which patients cannot reproduce simple designs (eg, a star), develops early. Agitation and mania can develop but are uncommon.

Asterixis is a characteristic flapping tremor that is elicited when patients hold their arms outstretched with wrists dorsiflexed. Neurologic deficits are usually symmetric. Neurologic signs in coma usually reflect bilateral diffuse hemispheric dysfunction.

Signs of brain stem dysfunction develop only in advanced coma, often during the hours or days before death. A musty, sweet breath odor (fetor hepaticus) can occur regardless of the stage of encephalopathy.

• Primarily history and physical examination

• Sometimes psychometric testing (for subtle neuropsychiatric deficits to help confirm early encephalopathy)

• Usually ammonia levels

• Usually EEG (usually showing diffuse slow-wave activity even in mild cases, sensitive but not specific for early encephalopathy)

• Exclusion of other treatable disorders

Cerebrospinal fluid examination is not routinely necessary; the only usual abnormality is mild protein elevation.

Other potentially reversible disorders that could cause similar manifestations (eg, infection, subdural hematoma, hypoglycemia, intoxication) should be exclude. If portosystemic encephalopathy is confirmed, the precipitating cause should be sought.

• Treatment of the cause

• Bowel cleansing using oral or rectal lactulose or oral polyethylene glycol 3350Bowel cleansing using oral or rectal lactulose or oral polyethylene glycol 3350

• Oral nonabsorbable antibiotics such as rifaximin and neomycinOral nonabsorbable antibiotics such as rifaximin and neomycin

Treating the cause usually reverses mild cases. Eliminating toxic enteric products is the other goal and is accomplished using several methods. The bowels should be cleared using enemas or, more often, oral lactulose syrup, which can be tube-fed to comatose patients. This synthetic disaccharide is an osmotic cathartic. It also lowers colonic pH, decreasing fecal ammonia production. The initial dosage should be adjusted to produce 2 or 3 soft stools daily. Protein restriction is not necessary and can be detrimental, as patients with cirrhosis are often malnourished. Treating the cause usually reverses mild cases. Eliminating toxic enteric products is the other goal and is accomplished using several methods. The bowels should be cleared using enemas or, more often, oral lactulose syrup, which can be tube-fed to comatose patients. This synthetic disaccharide is an osmotic cathartic. It also lowers colonic pH, decreasing fecal ammonia production. The initial dosage should be adjusted to produce 2 or 3 soft stools daily. Protein restriction is not necessary and can be detrimental, as patients with cirrhosis are often malnourished.

Oral nonabsorbable antibiotics such as rifaximin and neomycin are effective for hepatic encephalopathy acutely. Rifaximin is usually preferred because neomycin is an aminoglycoside, which can precipitate ototoxicity or nephrotoxicity. In refractory cases of encephalopathy one can consider the use of IV L-ornithine L-aspartate (Oral nonabsorbable antibiotics such as rifaximin and neomycin are effective for hepatic encephalopathy acutely. Rifaximin is usually preferred because neomycin is an aminoglycoside, which can precipitate ototoxicity or nephrotoxicity. In refractory cases of encephalopathy one can consider the use of IV L-ornithine L-aspartate (1, 2). Guidelines suggest that branched-chain amino acids may have a beneficial effect on HE, but in a randomized trial they did not prevent recurrence in patients with a previous episode of overt hepatic encephalopathy (3). In refractory cases of encephalopathy, one should look for other etiologies including a spontaneous shunt which may require embolization.

In chronic liver disease, correction of the precipitating cause usually causes encephalopathy to regress without permanent neurologic sequelae. Some patients, especially those with portacaval shunts or transjugular intrahepatic portosystemic shunting (TIPS), require continuous therapy; irreversible extrapyramidal signs or spastic paraparesis rarely develops. Coma (stage 4 encephalopathy) associated with fulminant hepatitis is fatal in up to 80% of patients despite intensive therapy; the combination of advanced chronic liver failure and portosystemic encephalopathy is often fatal.