What is Hepatic Encephalopathy?
Hepatic encephalopathy is a brain dysfunction caused by liver insufficiency and/or portosystemic shunting that manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma. 1
Core Pathophysiology
The condition results from two primary mechanisms that allow neurotoxins, particularly ammonia, to reach the brain 1:
- Liver insufficiency reduces the liver's capacity to detoxify ammonia and other neurotoxins 1
- Portosystemic shunting (PSS) allows portal blood to bypass the liver entirely, delivering toxins directly to systemic circulation 1, 2
The alterations in brain function produce behavioral, cognitive, and motor effects that were historically termed portosystemic encephalopathy before being consolidated under the term hepatic encephalopathy 1
Clinical Spectrum
HE exists on a continuum from minimal to severe manifestations 1:
Minimal/Covert HE (20-80% of cirrhotic patients)
- Only detectable through specialized psychometric testing 1
- Affects attention, working memory, psychomotor speed, and visuospatial ability 1
- Reduces quality of life and increases risk for overt HE 1
Overt HE (30-40% of cirrhotic patients during disease course)
- Personality changes: apathy, irritability, disinhibition 1
- Sleep-wake disturbances: excessive daytime sleepiness 1
- Progressive disorientation to time and space 1
- Motor abnormalities: asterixis (flapping tremor), hypertonia, hyperreflexia 1
- Advanced stages: confusion, stupor, coma 1
Classification Framework
HE must be classified according to four factors 1:
1. Underlying Disease Type
- Type A: Acute liver failure (distinct features, risk of cerebral herniation) 1
- Type B: Predominantly portosystemic bypass without cirrhosis 1, 2
- Type C: Cirrhosis with or without shunting 1
2. Severity of Manifestations
Graded using West Haven Criteria from minimal (subclinical) to Grade 4 (coma) 1
3. Time Course
- Episodic: discrete episodes 1
- Recurrent: episodes occurring ≤6 months apart 1
- Persistent: continuous behavioral alterations with intermittent worsening 1
4. Precipitating Factors
Common triggers include infections, gastrointestinal bleeding, constipation, sedatives, electrolyte disturbances, and dietary protein loads 1
Epidemiology and Prognosis
The prevalence correlates directly with liver disease severity 1:
- At cirrhosis diagnosis: 10-14% have overt HE 1
- Decompensated cirrhosis: 16-21% prevalence 1
- Post-TIPS procedure: 10-50% develop HE within one year 1
- Recurrence risk: 40% within 1 year after first episode, 40% within 6 months after recurrent episodes despite lactulose 1
Unless the underlying liver disease is successfully treated, HE is associated with poor survival and high recurrence risk 1. Even minimal HE increases risk for severe episodes and impairs quality of life 1
Key Clinical Pitfalls
Asterixis is Not Pathognomonic
While asterixis (negative myoclonus with loss of postural tone) is commonly present in early-to-middle stages of HE, it also occurs in uremia and other metabolic encephalopathies 1
Mental and Motor Signs May Dissociate
Cognitive/behavioral symptoms and motor abnormalities do not necessarily progress in parallel, creating difficulty in staging severity 1
Reversibility is Not Always Complete
Although traditionally considered fully reversible, emerging evidence suggests that repeated episodes of overt HE may cause persistent cumulative cognitive deficits 1
Non-Cirrhotic HE Exists
Large portosystemic shunts (congenital or spontaneous) can cause HE despite preserved liver synthetic function and absence of cirrhosis 2
Differential Diagnosis
The diagnosis requires excluding alternative causes of altered mental status 1:
- Metabolic: hypoglycemia, hyponatremia, hypercalcemia, uremia 1
- Toxic: alcohol intoxication/withdrawal, benzodiazepines, opioids 1
- Infectious: meningitis, encephalitis 1
- Neurological: stroke, intracranial bleeding, nonconvulsive seizures 1
- Psychiatric disorders 1
Hyponatremia and sepsis can both precipitate HE and cause encephalopathy independently, creating diagnostic complexity 1