Portosystemic Encephalopathy

Portosystemic encephalopathy may occur in fulminant hepatitis Fulminant Hepatitis Fulminant hepatitis is a rare syndrome of rapid (usually within days or weeks), massive necrosis of liver parenchyma and a decrease in liver size (acute yellow atrophy); it usually occurs after... read more caused by viruses, drugs, or toxins, but it more commonly occurs in cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more or other chronic disorders when extensive portosystemic collaterals have developed as a result of portal hypertension Portal Hypertension Portal hypertension is elevated pressure in the portal vein. It is caused most often by cirrhosis (in North America), schistosomiasis (in endemic areas), or hepatic vascular abnormalities. Consequences... read more . 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] Treatment ).

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. 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.

Diagnosis is ultimately based on clinical findings, but testing may help:

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 ruled out. If portosystemic encephalopathy is confirmed, the precipitating cause should be sought.

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 orally 3 times a day, should be adjusted to produce 2 or 3 soft stools daily. Contrary to prior practice, protein restriction is no longer necessary and can be detrimental, as cirrhotic patients are often malnourished. 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. However, there is no evidence that treatments such as lactulose or rifaximin help alleviate encephalopathy in acute liver failure Acute Liver Failure Acute liver failure is caused most often by drugs and hepatitis viruses. Cardinal manifestations are jaundice, coagulopathy, and encephalopathy. Diagnosis is clinical. Treatment is mainly supportive... read more .

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. Hemodialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more can help clear ammonia if there is acute liver failure. 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 Liver Transplantation Liver transplantation is the 2nd most common type of solid organ transplantation. (See also Overview of Transplantation.) Indications for liver transplantation include Cirrhosis (70% of transplantations... read more .

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.

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) Treatment , require continuous therapy, and irreversible extrapyramidal signs or spastic paraparesis rarely develops. Coma (stage 4 encephalopathy) associated with fulminant hepatitis Fulminant Hepatitis Fulminant hepatitis is a rare syndrome of rapid (usually within days or weeks), massive necrosis of liver parenchyma and a decrease in liver size (acute yellow atrophy); it usually occurs after... read more is fatal in up to 80% of patients despite intensive therapy; the combination of advanced chronic liver failure and portosystemic encephalopathy is often fatal.

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