II. Definition

  1. Brain dysfunction due to liver insufficiency or portosystemic shunting

III. Epidemiology

  1. Incidence: 30-40% of Cirrhosis patients within 5 years of Cirrhosis diagnosis
    1. Mild Impairment (Grade 1): 20-80% of cases
    2. Overt Hepatic Encephalopathy (Grades 2-4): 5-25% of cases

IV. Pathophysiology

  1. Severe liver disease resulting in liver failure
  2. Inability to eliminate Neurotoxins
    1. Ammonia
    2. Mercaptans
    3. Fatty Acids
    4. Gamma-aminobutyric acid (GABA)
  3. Other Mechanisms
    1. Astrocyte dysfunction
    2. Cerebral cellular swelling
    3. Blood-brain barrier disruption

V. Risk Factors: Precipitating Events

  1. Gastrointestinal Bleeding (especially Variceal Bleeding)
    1. Blood loss of 100 ml absorbed as 14-20 g Protein
  2. Azotemia
  3. Constipation
  4. High protein dietary intake
  5. Hypokalemic acidosis
  6. CNS depressants (e.g. Benzodiazepines)
  7. Hypoxia
  8. Hypercarbia
  9. Sepsis or other acute infection

VI. Symptoms and Signs

  1. Mild Disease (insidious onset)
    1. Day-night reversal
    2. Somnolence
    3. Confusion
    4. Personality change
    5. Asterixis (Flapping Tremor)
  2. Severe Disease
    1. Stupor
    2. Coma
    3. Dementia
    4. Extrapyramidal signs
    5. Fetor hepaticus (Odor of breath from mercaptans)

VII. Labs

  1. Markers correlated with Hepatic Encephalopathy
    1. International Normalized Ratio (INR)
    2. Venous total ammonia
    3. Ong (2003) Am J Med 114:188-93 [PubMed]
  2. Blood Ammonia Level (on ice)
    1. Not correlated with prognosis
    2. Normal ammonia level should prompt evaluation for other encephalopathy cause
  3. Consider Altered Mental Status Differential Diagnosis
    1. Comprehensive metabolic panel
    2. Blood Alcohol level
    3. Urine Toxicology Screening
    4. Serum Ketones
    5. Lactic Acid

VIII. Grading: West Haven Criteria Grading System

  1. Background
    1. Overt Hepatic Encephalopathy (OHE) seen in decompensated Cirrhosis refers to grades 2-4
  2. Grade 1
    1. Trivial lack of awareness
    2. Euphoria or anxiety
    3. Shortened attention span
    4. Impaired performance of addition or subtraction
  3. Grade 2
    1. Lethargy or apathy
    2. Minimal Disorientation for time or place
    3. Subtle personality change
    4. Inappropriate behavior
  4. Grade 3
    1. Somnolence to semi-stupor
    2. Responsive to verbal stimuli
    3. Confusion
    4. Gross Disorientation
  5. Grade 4
    1. Coma (unresponsive to verbal or noxious stimuli)
  6. References
    1. Ferenci (2002) Hepatology 335(3): 716-21 [PubMed]

X. Diagnostics

XI. Management

  1. Initial Measures (effective in up to 90% of cases)
    1. ABC Management (especially airway)
    2. Avoid and correct precipitating factors listed above
    3. Reduce blood ammonia
      1. Lactulose (key management)
        1. Dose: 30-45 ml syrup PO titrated to qid or
        2. Retention enema 300 ml until >1 stool/day
      2. Decrease protein intake
        1. Limit to 20-30 g/day
        2. Protein restriction may not be needed
          1. Cordoba (2004) J Hepatol 41:38-43 [PubMed]
  2. Refractory cases
    1. Rifamaxin
    2. Neomycin 4-12 grams orally divided q6-8 hours
    3. Consider unproven or experimental methods
      1. IV branched chain amino acids
      2. Bromocriptine (may improve extrapyramidal symptoms)
      3. Flumazenil (may improve mental status)
      4. Lactilol (alternative to Lactulose)

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Ontology: Hepatic Encephalopathy (C0019151)

Definition (MSHCZE) Soubor neurologických a psychiatrických příznaků vznikajících při jaterním onemocnění. Má částečně odlišný charakter při současné portální hypertenzi (viz encefalopatie portosystémová) či při akutním selhání s výraznou nekrózou hepatocytů. E. při akutním selhání je obv. provázena edémem mozku. JAterní encefalopatie - neurologické a psychiatrické projevy poškození mozku při jaterním selhání. Má poměrně různorodé projevy vyjádřené s různou intenzitou (akutní, chronická j. e.). Způsob, jakým vede jaterní porucha k j. e., není ještě zcela objasněn, nejuznávanější teorie předpokládá, že je kóma způsobeno poruchou metabolismu dusíku. V závislosti na stupni poruchy vědomí se rozlišují 4 stadia: prodromální (poruchy koncentrace, spánku a pozornosti, euforie nebo deprese), hrozící kóma (spavost, zpomalené reakce, flapping tremor), stupor (dezorientace, neartikulovaná řeč), kóma (hluboké bezvědomí, foetor hepaticus). J. e. může vyústit do jaterního kómatu. Viz encefalopatie portosystémová (cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ )
Definition (NCI) A constellation of signs and symptoms characterized by changes in personality, consciousness, and reflexes, resulting from neuropsychiatric abnormalities secondary to liver failure without evidence of other brain disease.
Definition (CSP) syndrome characterized by central nervous system dysfunction in association with liver failure, including portal-systemic shunts; clinical features include lethargy and confusion, frequently progressing to coma, asterixis, nystagmus, brisk oculovestibular reflexes, decorticate and decerebrate posturing, muscle spasticity, and bilateral extensor plantar reflexes.
Definition (MSH) A syndrome characterized by central nervous system dysfunction in association with LIVER FAILURE, including portal-systemic shunts. Clinical features include lethargy and CONFUSION (frequently progressing to COMA); ASTERIXIS; NYSTAGMUS, PATHOLOGIC; brisk oculovestibular reflexes; decorticate and decerebrate posturing; MUSCLE SPASTICITY; and bilateral extensor plantar reflexes (see REFLEX, BABINSKI). ELECTROENCEPHALOGRAPHY may demonstrate triphasic waves. (From Adams et al., Principles of Neurology, 6th ed, pp1117-20; Plum & Posner, Diagnosis of Stupor and Coma, 3rd ed, p222-5)
Concepts Disease or Syndrome (T047)
MSH D006501
ICD9 572.2
ICD10 K72
SnomedCT 123049003, 13920009, 449902003, 197332007
English Encephalopathies, Hepatic, Encephalopathies, Portosystemic, Encephalopathy, Portosystemic, Hepatic Encephalopathies, Portosystemic Encephalopathies, Portosystemic Encephalopathy, Encephalopathy, Hepatic, HEPATIC ENCEPHALOPATHY, ENCEPH HEPATOCEREBRAL, ENCEPH PORTAL SYSTEMIC, HEPATIC ENCEPH, PORTOSYSTEMIC ENCEPH, ENCEPH PORTOSYSTEMIC, PORTAL SYSTEMIC ENCEPH, HEPATOCEREBRAL ENCEPH, ENCEPH HEPATIC, hepatic encephalopathy, portacaval encephalopathy, hepatocerebral syndrome, hepatic encephalopathy (diagnosis), Encephalopathy hepatic, Encephalopathies, Hepatocerebral, Encephalopathy, Hepatocerebral, Hepatocerebral Encephalopathies, Hepatocerebral Encephalopathy, Encephalopathies, Portal-Systemic, Encephalopathy, Portal-Systemic, Portal Systemic Encephalopathy, Portal-Systemic Encephalopathies, Portal-Systemic Encephalopathy, hepatic encephalopathy NOS, Hepatic Encephalopathy [Disease/Finding], portal-systemic encephalopathy, encephalopathy hepatic, encephalopathy portosystemic, coma hepaticum, portal systemic encephalopathy, portosystemic encephalopathy, hepatic coma/encephalopathy, Encephalopathy, Portal Systemic, Gaustad's syndrome, Portal systemic encephalopathy (disorder), Portal systemic encephalopathy, Transient hepatargy syndrome, Encephalopathy - hepatic, Hepatocerebral encephalopathy (disorder), Hepatocerebral encephalopathy, Hepatic encephalopathy, HE - Hepatic encephalopathy, Hepatic encephalopathy (disorder), encephalopathy; hepatic, encephalopathy; portosystemic, hepatic; encephalopathy, portosystemic; encephalopathy, Hepatocerebral encephalopathy -RETIRED-, Hepatic Encephalopathy, Portal-systemic encephalopathy
Dutch encefalopathie hepatisch, encefalopathie; hepatisch, encefalopathie; porta-systeem, hepatisch; encefalopathie, porta-systeem; encefalopathie, hepatische encefalopathie, Encefalopathie, hepatische, Hepatische encefalopathie, Portosystemische encefalopathie
German Enzephalopathie, hepatisch, hepatische Enzephalopathie, Hepatische Enzephalopathie, Portosystemische Enzephalopathie, Enzephalopathie, hepatische
Swedish Leverencefalopati
Japanese カンセイノウショウ, 門脈系脳症, 肝性脳障害, 肝性脳症, 肝性昏睡
Czech jaterní encefalopatie, Hepatální encefalopatie, Encefalopatie hepatální, portosystémová encefalopatie, hepatocerebrální encefalopatie
Finnish Hepaattinen enkefalopatia
Italian Encefalopatia porto-sistemica, Encefalopatia portosistemica, Encefalopatia epatocerebrale, Encefalopatia epatica
Russian PECHENOCHNAIA ENTSEFALOPATIIA, PORTOSISTEMNAIA ENTSEFALOPATIIA, PECHENOCHNAIA NEDOSTATOCHNOST' MOLNIENOSNAIA, PECHENOCHNAIA KOMA, ENTSEFALOPATIIA PECHENOCHNAIA, GEPATARGIIA, ГЕПАТАРГИЯ, ПЕЧЕНОЧНАЯ КОМА, ПЕЧЕНОЧНАЯ НЕДОСТАТОЧНОСТЬ МОЛНИЕНОСНАЯ, ПЕЧЕНОЧНАЯ ЭНЦЕФАЛОПАТИЯ, ПОРТОСИСТЕМНАЯ ЭНЦЕФАЛОПАТИЯ, ЭНЦЕФАЛОПАТИЯ ПЕЧЕНОЧНАЯ
Croatian JETRENA ENCEFALOPATIJA
Polish Encefalopatia wątrobowa, Śpiączka wątrobowa
Hungarian Hepatikus encephalopathia, Encephalopathia, hepatikus
Norwegian Leverencefalopati, Hepatisk encefalopati, Encefalopati, hepatisk
Spanish encefalopatía portal sistémica (trastorno), encefalopatía portal sistémica, encefalopatía hepatocerebral - RETIRADO - (concepto no activo), encefalopatía hepatocerebral - RETIRADO -, encefalopatía hepatocerebral, encefalopatía hepática (trastorno), encefalopatía hepática, encefalopatía portosistémica, síndrome de Gaustad, síndrome de hepargia transitoria, Encefalopatía hepática, Encefalopatía Hepática, Encefalopatía Portosistémica
Portuguese Encefalopatia hepática, Encefalopatia Hepática, Encefalopatia Portossistêmica
French Encéphalopathie hépatique, Encéphalopathie porto-cave