(See also Liver Structure and Function and Evaluation of the Patient With a Liver Disorder.)
Portosystemic encephalopathy better describes the pathophysiology than hepatic encephalopathy or hepatic coma, but all 3 terms are used interchangeably.
Etiology of Portosystemic Encephalopathy
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]).
Precipitants
In patients with chronic liver disease, acute episodes of encephalopathy are usually precipitated by reversible causes. The most common are the following:
Metabolic stress (eg, infection; electrolyte imbalance, especially hypokalemia; dehydration; use of diuretic drugs)
Conditions that increase gut protein (eg, gastrointestinal bleeding, high-protein diet)
Nonspecific cerebral depressants (eg, alcohol, sedatives, analgesics)
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
Symptoms and signs of encephalopathy tend to develop in progressive stages (see table Clinical Stages of Portosystemic Encephalopathy).
Clinical Stages of Portosystemic Encephalopathy
Stage | Cognition and Behavior | Neuromuscular Function |
|---|---|---|
0 (subclinical) | Asymptomatic loss of cognitive abilities | None |
1 | Sleep disturbances Impaired concentration Depression, anxiety, or irritability | Monotone voice Tremor Poor handwriting Constructional apraxia |
2 | Drowsiness Disorientation Poor short-term memory Disinhibited behavior | Ataxia Dysarthria Asterixis Automatisms (eg, yawning, blinking, sucking) |
3 | Somnolence Confusion Amnesia Anger, paranoia, or other bizarre behavior | Nystagmus Muscular rigidity Hyperreflexia or hyporeflexia |
4 | Coma | Dilated pupils Oculocephalic or oculovestibular reflexes Decerebrate posturing |
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.
Treatment of Portosystemic Encephalopathy
Treatment of the cause
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 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.
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), 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.
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).
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
American Association for the Study of Liver Diseases and the European Association for the Study of the Liver: Hepatic Encephalopathy in Chronic Liver Disease 2014 Practice Guidelines
