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Portal-Systemic Encephalopathy Clinical Presentation

  • Author: Gagan K Sood, MD; Chief Editor: BS Anand, MD  more...
Updated: Dec 18, 2014


The patient may present with vague complaints, such as fatigue, or they may be brought for evaluation by relatives. Indeed, the family members of patients often are the most useful historians. They may describe restlessness (especially at night), somnolence (typically during the day), and instances reflecting episodic confusion.

  • No neurologic features are entirely specific for this disorder.
  • Clinical history or physical examination findings suggestive of liver disease, without evidence of another etiology for neurological dysfunction, form the basis for the diagnosis.
  • A precipitating factor identified from the clinical history strongly suggests the diagnosis. Therefore, directed questioning in this regard is essential.
  • Several predisposing conditions also may contribute to the development of chronic portosystemic encephalopathy.


As with many toxic and metabolic encephalopathies, mental status and, in particular, level of consciousness may fluctuate dramatically. In addition to impairment of the level of consciousness, patients with portosystemic encephalopathy may demonstrate a variety of neurologic signs together or in isolation.

  • The grades of portosystemic encephalopathy are as follows:
    • Subclinical portosystemic encephalopathy: Early in the course of portosystemic encephalopathy, patients may appear normal clinically but perform poorly on psychometric testing. This is termed subclinical portosystemic encephalopathy. This condition may be particularly important to diagnose in patients performing tasks that require rapid reaction times because these are prolonged in patients with subclinical portosystemic encephalopathy. Judgment also may be erratic or questionable. Recognition of subtle impairment, therefore, may lead to a recommendation to avoid driving an automobile or operating machinery.
    • Grade 1 portosystemic encephalopathy: With deterioration to grade 1 portosystemic encephalopathy, the examination reveals difficulty with memory, mild confusion, agitation, and irritability. Patient complaints may include restlessness or sleeping during the day and remaining awake at night. Tremor, a rhythmic or regular oscillation, and incoordination may be seen. Handwriting skills typically are impaired. Constructional apraxia may be easily demonstrated at the bedside by requesting the patient to draw a 5-pointed star.
    • Grade 2 portosystemic encephalopathy: Progression to grade 2 portosystemic encephalopathy involves a slowing of mentation and speech, with the appearance of lethargy. The patient's confusion progresses to difficulty with orientation to time, and loss of inhibition ultimately may result in inappropriate behavior. Neurologic signs include asterixis and an irregular flapping tremor that is observed best with the wrists dorsiflexed and fingers spread. Dysarthria, ataxia, and hypoactive deep-tendon reflexes are characteristic.
    • Grade 3 portosystemic encephalopathy: This grade portends the significant possibility of coma; therefore, plans to perform endotracheal intubation should be made upon recognition of this state. Patients are drowsy but can be woken up; however, they remain markedly confused. They may exhibit frankly aggressive behavior. Asterixis persists, but the deep-tendon reflexes become hyperactive as they are disinhibited, a process that culminates in the development of the decerebration seen in grade 4. Babinski signs may be seen.
    • Grade 4 portosystemic encephalopathy: This also is known as hepatic coma and represents a medical emergency. Patients are able to protect their airway reliably. Prophylactic endotracheal intubation is mandatory. Patients may remain unresponsive for several days.
  • Stigmata of chronic liver disease and portal hypertension may be evident upon examination. These include the presence of gynecomastia and testicular atrophy in males, palmar erythema, spider nevi, splenomegaly, caput medusae, ascites, peripheral edema, and a shrunken liver.
  • More specific signs resulting from the underlying liver diseases also may be present, as follows:
    • The Kayser-Fleischer rings of Wilson disease typically are identified only with slit-lamp examination.
    • Bronzed skin and arthropathy are seen in hereditary hemochromatosis.
    • Cholesterol deposition may be seen as xanthelasma in patients with chronic cholestasis of any cause, but it often is most striking in primary biliary cirrhosis.
    • Alcoholic liver disease frequently is accompanied by advanced malnutrition; however, any long-standing liver disease also may lead to temporal, shoulder girdle, and hip girdle muscle wasting.
    • Cutaneous features of hepatitis C virus infection include a characteristic rash due to leukocytoclastic vasculitis resulting from mixed cryoglobulinemia, porphyria cutanea tarda, and lichen planus.


Precipitating factors that lead to clinical manifestations of portosystemic encephalopathy may be obvious; however, often a cause is not evident despite concerted efforts to identify one. The importance of trying to determine the precipitating cause cannot be overemphasized. Infection, specifically SBP, is especially important to exclude. Several known causes are categorized below by their proposed mechanisms. In some cases, multiple mechanisms may be responsible.

  • Increased ammoniagenesis
    • Increased substrate (protein) for ammoniagenesis
    • Increased protein intake
    • Gastrointestinal bleeding
    • Constipation
    • Dehydration
    • Increased substrate (urea) for ammoniagenesis
    • Renal failure
    • Increased catabolism of protein
    • Infection
    • Hypokalemia
    • Sepsis
  • Decreased hepatocellular function
    • Dehydration
    • Hypotension
    • Sepsis
    • Hypoxia
    • Anemia
    • Development of hepatocellular carcinoma
    • Worsened intrinsic liver disease
    • Drug toxicity
    • Superimposed viral hepatitis
  • Increased portocaval shunting
    • Portal vein thrombosis
    • Transjugular intrahepatic portosystemic shunt formation
    • Surgical shunt formation
    • Spontaneous shunt formation
  • Psychoactive drug use
    • Benzodiazepines
    • Ethanol
    • Antinauseants
    • Antihistamines
    • Others
  • Other mechanisms
    • Increased diffusion of ammonia across the blood-brain barrier: Alkalosis may occur, which promotes ammonium ion conversion to less polar and more diffusible ammonia.
    • Blood transfusion: Increased ammoniagenesis from transfusions may not be entirely accurate and possibly is a more theoretical than practical concern. Glutaminase activity and generation of ammonia in stored cellular blood products (especially platelets) may conceivably lead to infusion of ammonia during transfusion.
Contributor Information and Disclosures

Gagan K Sood, MD Associate Professor, Department of Medicine and Surgery, Baylor College of Medicine

Gagan K Sood, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Noel Williams, MD, FRCPC FACP, MACG, Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada

Noel Williams, MD, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Additional Contributors

Ann Ouyang, MBBS Professor, Department of Internal Medicine, Pennsylvania State University College of Medicine; Attending Physician, Division of Gastroenterology and Hepatology, Milton S Hershey Medical Center

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor, Blake A Jones, MD, to the development and writing of this article.

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