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Portosystemic Encephalopathy

By

Danielle Tholey

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Last full review/revision Jan 2021| Content last modified Jan 2021
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Portosystemic encephalopathy is a neuropsychiatric syndrome that can develop in patients with liver disease. It most often results from high gut protein or acute metabolic stress (eg, gastrointestinal 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, oral lactulose, and nonabsorbable antibiotics such as rifaximin.

Portosystemic encephalopathy better describes the pathophysiology than hepatic encephalopathy or hepatic coma, but all 3 terms are used interchangeably.

Etiology of Portosystemic Encephalopathy

Precipitants

In patients with chronic liver disease, acute episodes of encephalopathy are usually precipitated by reversible causes. The most common are the following:

Pathophysiology of Portosystemic Encephalopathy

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 Portosystemic Encephalopathy

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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 of Portosystemic Encephalopathy

  • Clinical evaluation

  • Often adjunctive testing with psychometric evaluation, ammonia level, electroencephalogram (EEG), or a combination

  • Exclusion of other treatable disorders

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

  • Psychometric testing may reveal subtle neuropsychiatric deficits, which can help confirm early encephalopathy.

  • Ammonia levels are usually measured.

  • An EEG usually shows diffuse slow-wave activity, even in mild cases, and may be sensitive but is not specific for early encephalopathy.

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.

Prognosis for Portosystemic Encephalopathy

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) Portal hypertension is elevated pressure in the portal vein. It is caused most often by cirrhosis (in developed countries), schistosomiasis (in endemic areas), or hepatic vascular abnormalities... read more , 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.

Treatment of Portosystemic Encephalopathy

  • Treatment of the cause

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

  • Oral 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, 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.

More Information

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

Key Points

  • 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, gastrointestinal bleeding, electrolyte abnormality).

  • Treat the cause of encephalopathy and treat encephalopathy itself with bowel cleansing (using oral or rectal lactulose or oral polyethylene glycol 3350 or enemas) and oral rifaximin or neomycin.

Drugs Mentioned In This Article

Drug Name Select Trade
PARLODEL
No US brand name
XIFAXAN
CHOLAC
Levodopa
NEO-FRADIN
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