Portosystemic encephalopathy is a neuropsychiatric syndrome. It most often results from high gut protein or acute metabolic stress (eg, GI bleeding, infection, electrolyte abnormality) in a patient with portosystemic shunting. Symptoms are mainly neuropsychiatric (eg, confusion, asterixis, coma). Diagnosis is based on clinical findings. Treatment is usually correction of the acute cause, a diet that includes vegetable protein as the primary protein source, oral lactulose, and nonabsorbable antibiotics such as rifaximin.
(See also the American College of Gastroenterology’s practice guideline Hepatic Encephalopathy.) Portosystemic encephalopathy better describes the pathophysiology than hepatic encephalopathy or hepatic coma, but all 3 terms are used interchangeably.
Portosystemic encephalopathy may occur in fulminant hepatitis caused by viruses, drugs, 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 patients with chronic liver disease, acute episodes of encephalopathy are usually precipitated by reversible causes. The most common are the following:
In portosystemic shunting, absorbed products that would otherwise be detoxified by the liver enter the systemic circulation and reach the brain, causing toxicity, 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).
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. A characteristic flapping tremor (asterixis) 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.
Diagnosis is ultimately based on clinical findings, but testing may help:
CSF 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 ruled out. If portosystemic encephalopathy is confirmed, the precipitating cause should be sought.
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 TIPS, require continuous therapy, and 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.
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, 30 to 45 mL po tid, should be adjusted to produce 2 or 3 soft stools daily. Dietary protein should be about 1.0 mg/kg/day, primarily from vegetable sources. Oral nonabsorbable antibiotics such as rifaximin and neomycin are effective for hepatic encephalopathy. Rifaximin is usually preferred because neomycin is an aminoglycoside, which can precipitate ototoxicity or nephrotoxicity.
Sedation deepens encephalopathy and should be avoided whenever possible. For coma caused by fulminant hepatitis, meticulous supportive and nursing care coupled with prevention and treatment of complications increase the chance of survival. High-dose corticosteroids, exchange transfusion, and other complex procedures designed to remove circulating toxins generally do not improve outcome. Patients deteriorating because of fulminant hepatic failure may be saved by liver transplantation.
Other potential therapies, including levodopa, bromocriptine, flumazenil, sodium benzoate, infusions of branched-chain amino acids, keto-analogs of essential amino acids, and prostaglandins, have not proved effective. Complex plasma-filtering systems (artificial liver) show some promise but require more study.
Portosystemic encephalopathy is a neuropsychiatric syndrome that occurs when portosystemic shunting allows absorbed products that are normally detoxified by the liver to reach the brain.
Manifestations include cognitive and behavioral dysfunction (eg, confusion, obtundation, coma) and neuromuscular dysfunction (eg, flapping tremor, ataxia, hyperreflexia or hyporeflexia).
Diagnose portosystemic encephalopathy based mainly on clinical findings, but usually measure the blood ammonia level, and if signs are subtle or absent, do neuropsychologic testing.
Exclude other treatable disorders (eg, subdural hematoma, hypoglycemia, intoxication), and search for triggers of encephalopathy (eg, infection, GI bleeding, electrolyte abnormality).
Treat the cause of encephalopathy and treat encephalopathy itself with bowel cleansing (using oral lactulose or enemas), restriction of dietary protein to vegetable sources, and oral rifaximin or neomycin.