CNS nontumor

Toxic and metabolic disorders

Hepatic encephalopathy


Resident / Fellow Advisory Board: Meaghan Morris, M.D., Ph.D.
Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D.
Palgun Nisarga, M.D.
Kymberly A. Gyure, M.D.

Topic Completed: 13 September 2021

Minor changes: 13 September 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Hepatic encephalopathy [title] CNS


Palgun Nisarga, M.D.
Kymberly A. Gyure, M.D.
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Cite this page: Nisarga P, Gyure KA. Hepatic encephalopathy. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnshepatic.html. Accessed October 16th, 2021.
Definition / general
  • Spectrum of neurocognitive abnormalities occurring in patients with acute or chronic liver disease or portosystemic shunting
Essential features
  • Clinical pattern and pathology are not dependent on the etiology of liver disease
  • Characterized by neurocognitive abnormalities
  • Elevated blood ammonia levels considered to play central role
  • Histologic hallmark - Alzheimer type II astrocyte - enlarged, pale nuclei with a rim of chromatin
Terminology
  • Hepatic encephalopathy (HE)
  • Portosystemic encephalopathy
ICD coding
  • ICD-9:
    • 572.2 - hepatic encephalopathy
  • ICD-10:
    • K72.91 - hepatic failure, unspecified with coma
    • K70.41 - alcoholic hepatic failure with coma
    • K72.11 - chronic hepatic failure with coma
    • K71.11 - toxic liver disease with hepatic necrosis, with coma
    • K72.01 - acute and subacute hepatic failure with coma
Epidemiology
  • Chronic alcoholism, acute drug poisoning, status post portosystemic bypass, hepatic failure patients
Sites
  • Gray matter astrocytes
Pathophysiology
  • Acute hepatic encephalopathy: cerebral edema and increased intracranial pressure (cause of death)
  • Pathophysiology of hepatic encephalopathy is multifactorial
  • Postulated agents include ammonia (NH3), inflammatory cytokines, manganese deposition in the basal ganglia, benzodiazepine-like compounds (GABA), microbiota and aromatic amino acids (Drugs 2019;79:17)
  • Ammonia has been considered to play a central role in HE (see Diagrams / tables)
Etiology
  • HE type A: HE associated with acute liver failure (e.g. acetaminophen overdose)
  • HE type B: HE associated with portosystemic bypass in the absence of hepatic disease
  • HE type C: HE associated with cirrhosis and portal hypertension or portosystemic bypass
  • Reference: Hepatology 2002;35:716
Diagrams / tables

Contributed by Palgun Nisarga, M.D.
Ammonia and hepatic encephalopathy

Ammonia and hepatic encephalopathy

Clinical features
  • Disorientation, behavioral and personality changes, including somnolence, agitation, anger and restlessness
  • Motor abnormalities, including Parkinsonism, choreoathetosis, spastic paraparesis with hyperreflexia and slowness of speech
  • Dementia-like pattern and sleep disturbances
  • May be precipitated by infection, gastrointestinal bleeding, medication noncompliance, electrolyte imbalance / renal failure or acute liver injury
  • Clinical patterns: coma, rapidly developing confusion (somnolent or agitated), continuous mild mental dysfunction with recurrent episodes of severe confusion, predominant motor disorder (pyramidal and extrapyramidal) or mild brain dysfunction (J Clin Exp Hepatol 2018;8:432)
  • Asterixis in alcoholic liver disease
Diagnosis
  • Based predominantly on clinical features
  • West Haven criteria used to grade severity (Hepatology 2002;35:716)
Laboratory
  • Serum ammonia levels may be elevated
Radiology description
  • Symmetric, hyperintense signal in the basal ganglia, especially the globus pallidus, on T1 weighted MR images
  • Restricted diffusion in the cerebral cortex (diffusion weighted imaging)
  • Reference: AJNR Am J Neuroradiol 2008;29:1612
Prognostic factors
  • Prognosis based on percent of viable hepatic parenchyma in acute hepatic failure
  • Necrosis > 50% in liver biopsy - threshold for liver transplantation (Clin Liver Dis 2018;22:257)
  • Poor prognosis independent of severity of liver disease and despite treatment advances; 1 year survival approximately 20 - 40% (World J Gastroenterol 2020;26:2221)
Case reports
Treatment
  • Treatment of precipitating event
  • Reduce blood ammonia concentration using nonabsorbable disaccharides or antibiotics
  • Liver transplantation
  • Reference: Aliment Pharmacol Ther 2010;31:537
Gross description
  • Acute hepatic encephalopathy: cerebral edema with herniation
  • Chronic hepatic encephalopathy: brain is typically normal grossly
  • Reference: N Engl J Med 2016;375:1660
Microscopic (histologic) description
  • Alzheimer type II astrocytes: enlarged, pale nuclei with a rim of chromatin and a prominent nucleoli
  • Astrocyte doublets / pairs and triplets are seen
  • Severe disease: astrocyte nucleus appears lobulated and contains glycogen granules
  • Most commonly seen in gray matter regions, including globus pallidus, putamen, pons, thalamus, dentate nucleus and cortical gray matter (deep layers)
  • Acute hepatic encephalopathy: brain edema due to swelling of perivascular astrocytes (Hepatology 1992;15:1060)
  • Reference: J Neuropathol Exp Neurol 1994;53:213
Microscopic (histologic) images

Contributed by Kymberly A. Gyure, M.D. and Palgun Nisarga, M.D.
Alzheimer type II astrocyte Alzheimer type II astrocyte

Alzheimer type II astrocyte

Positive stains
Negative stains
  • Severe disease: astrocytes lose immunoreactivity to GFAP
Sample pathology report
  • History of cirrhosis with hepatic encephalopathy
    • Alzheimer type II astrocytosis
Differential diagnosis
  • Differential diagnosis is investigated from a clinicoradiological standpoint
  • Clinically should be distinguished from stroke
  • Alzheimer type II astrocytes also seen in uremic encephalopathy, hypercapnic encephalopathy and in infants with hypoxia and hypoglycemia; their distinction from hepatic encephalopathy is based on clinical and radiologic features, not pathology
Board review style question #1
Which of the following is the most likely cause of death in a patient with acute hepatic encephalopathy?

  1. Acute renal failure
  2. Bleeding diathesis
  3. Cerebral edema
  4. Hypoglycemia
  5. Myocardial necrosis
Board review style answer #1
C. Cerebral edema and herniation are common in acute hepatic encephalopathy

Comment Here

Reference: Hepatic encephalopathy
Board review style question #2

Which part of the CNS most commonly shows increased Alzheimer type II astrocytes?

  1. Basal ganglia
  2. Brain stem
  3. Cerebellum
  4. Cerebral cortex
  5. Internal capsule
Board review style answer #2
A. Alzheimer type II astrocytes are most commoly found in the basal ganglia, especially the globus pallidus

Comment Here

Reference: Hepatic encephalopathy
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