What are the signs of hepatic encephalopathy?

Signs of Hepatic Encephalopathy

Hepatic encephalopathy (HE) produces a wide spectrum of neurological and psychiatric manifestations ranging from subtle cognitive deficits to coma, with characteristic motor abnormalities including asterixis being a key diagnostic sign. 1

Neuropsychiatric Manifestations

Early Signs (Minimal/Covert HE)

• Alterations in attention, working memory, psychomotor speed, and visuospatial ability 1
• Personality changes reported by relatives: apathy, irritability, and disinhibition 1
• Sleep-wake cycle disturbances with excessive daytime sleepiness 1

Progressive Signs (Overt HE)

• Progressive disorientation to time and space 1
• Inappropriate behavior and acute confusional state 1
• Agitation or somnolence, progressing to stupor and coma in severe cases 1

Motor Abnormalities

Characteristic Motor Signs

• Asterixis ("flapping tremor"): a negative myoclonus consisting of loss of postural tone, easily elicited by hyperextension of wrists with separated fingers 1
  • Can be observed in hands, feet, legs, arms, tongue, and eyelids
  • Present in early to middle stages of HE before stupor/coma
  • Not pathognomonic (also seen in uremia and other conditions)

Pyramidal Signs

• Hypertonia, hyperreflexia, and positive Babinski sign in noncomatose patients 1, 2
• Deep tendon reflexes may diminish and disappear in coma 1
• Rarely, transient focal neurological deficits 1

Extrapyramidal Dysfunction

• Hypomimia (reduced facial expression) 1, 2
• Muscular rigidity 1, 2
• Bradykinesia and hypokinesia 1, 2
• Monotony and slowness of speech 1, 2
• Parkinsonian-like tremor 1, 2
• Dyskinesia with diminished voluntary movements 1, 2
• Rarely, involuntary movements similar to tics or chorea 1

Special Clinical Variants

Hepatic Myelopathy

• Severe motor abnormalities exceeding mental dysfunction 1, 2
• Progressive spasticity and weakness of lower limbs with hyperreflexia 1, 2
• Relatively mild persistent or recurrent mental alterations 1
• Does not respond to standard ammonia-lowering therapy 1
• May reverse with liver transplantation 1

Cirrhosis-Associated Parkinsonism

• Prominent extrapyramidal and/or pyramidal signs 1, 2
• Unresponsive to ammonia-lowering therapy 1
• Occurs in approximately 4% of patients with advanced liver disease 1, 2
• Previously called acquired hepatolenticular degeneration (now obsolete term) 1

Clinical Pitfalls and Caveats

• Mental and motor signs may not progress in parallel, making staging difficult 1
• Asterixis is not specific to HE (also seen in uremia and other conditions) 1
• Seizures are very rarely reported in HE 1
• While generally considered reversible, repeated episodes of overt HE may be associated with persistent cumulative deficits in working memory and learning 1
• Thiamine deficiency (particularly in alcoholic liver disease) can cause similar cerebral symptoms that cannot be differentiated from HE by clinical examination alone 1
• Always exclude other causes of altered mental status in patients with liver disease before attributing symptoms solely to HE 1

Early recognition of these signs is critical for timely intervention with ammonia-lowering strategies such as lactulose 3 and rifaximin 4, which can improve outcomes and reduce morbidity and mortality associated with hepatic encephalopathy.