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Hepatic encephalopathy

Definition
HE is a reversible neuropsychiatric abnormality found in patients with chronic liver disease and/or portosystemic shunting.
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Pathophysiology
The pathophysiology of HE is multifactorial and involves agents such as ammonia, inflammatory cytokines, manganese deposition in the basal ganglia, and benzodiazepine-like compounds. Fecal microbiota and aromatic amino acids also play a role.
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Epidemiology
In the US, the incidence of hospital admission for HE is approximately 30 cases per 100,000 person-years. In patients with decompensated cirrhosis, the prevalence of HE is up to 20%.
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Disease course
HE is associated with clinical manifestations of neuronal dysfunction (delirium, seizures). If untreated, severe HE may result in brain edema, coma, and death.
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Prognosis and risk of recurrence
The in-hospital mortality of patients with HE is estimated at 14.1-15.6%. Patients with cirrhosis who develop HE have an estimated 1-year survival probability of 42% and 3-year survival probability of 23%.
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Key sources
The following summarized guidelines for the evaluation and management of hepatic encephalopathy are prepared by our editorial team based on guidelines from the Society of Critical Care Medicine (SCCM 2023), the European Association for the Study of the Liver (EASL 2022; 2018), the Baveno VII Consensus Workshop (Baveno VII 2022), the Italian Association for the Study of the Liver (AISF 2019), and the European Association for the Study of the Liver (EASL/AASLD 2014).
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Guidelines

1.Screening and diagnosis

Screening for covert hepatic encephalopathy: as per EASL 2022 guidelines, screen patients with cirrhosis and no history of overt HE for covert HE with validated (with available experience/tools and local norms) tests.
B
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  • Diagnosis

  • Differential diagnosis

2.Classification and risk stratification

Classification: as per EASL 2022 guidelines, classify HE according to the underlying condition:
Situation
Guidance
Type A
ALF
Type B
Portosystemic shunt
Type C
Cirrhosis
B
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  • Severity grading

3.Diagnostic investigations

Serum ammonia levels: as per EASL 2022 guidelines, obtain serum ammonia level measurement in patients with delirium/encephalopathy and liver disease, as a normal value brings the diagnosis of HE into question.
B

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  • Neurophysiological testing

  • Brain imaging

  • Abdominal imaging

4.Respiratory support

Mechanical ventilation: consider intubating patients with grades III-IV HE.
C

5.Medical management

Setting of care
As per EASL 2022 guidelines:
Admit patients with grades 3-4 overt HE to the ICU as they are at risk of aspiration.
B
Admit patients with HE to the ICU based on clinical judgment as there is no single marker that can identify patients who will benefit from ICU admission.
B

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  • Management of precipitating factors

  • Indications for treatment

  • Nonabsorbable disaccharides

  • Oral branched-chain amino acids

  • Intravenous L-ornithine L-aspartate

  • Dopaminergic agents

  • Antibiotic therapy

  • Diuretic therapy

  • Discontinuation of treatment

6.Inpatient care

Serial clinical assessment: assess for signs of intracranial hypertension at regular intervals and monitor for ICP and manage according to available pertinent guidelines.
B

7.Nonpharmacologic interventions

Dietary modifications: as per EASL 2022 guidelines, consider replacing animal protein with vegetable and dairy protein in patients with recurrent/persistent HE, taking into account the patient's tolerance, provided that overall protein intake is not compromised.
C

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  • Vitamin and micronutrient supplements

8.Therapeutic procedures

Albumin dialysis: consider performing albumin dialysis to ameliorate HE in patients with liver failure and overt HE.
C

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  • Occlusion of portosystemic shunts

  • Liver support system

  • Fecal microbiota transplantation

9.Perioperative care

Pre-transjugular intrahepatic portosystemic shunt prophylaxis
Consider administering rifaximin for prophylaxis of HE before non-urgent TIPS placement in patients with cirrhosis and previous episodes of overt HE.
B
Assess for the presence and/or history of overt and covert HE in patients scheduled for a non-urgent TIPS placement. Recognize that one single episode of HE is not an absolute contraindication, especially if precipitated by bleeding.
B

10.Surgical interventions

Liver transplantation: as per EASL 2022 guidelines, consider performing liver transplantation in patients with recurrent/persistent HE. Refer patients promptly to a center for evaluation in case of the first episode of overt HE.
B
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11.Specific circumstances

Patients with acute-on-chronic liver failure: consider administering nonabsorbable disaccharides in critically ill patients with acute-on-chronic liver failure and overt HE.
C
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12.Patient education

General counseling: counsel patients with a history of overt HE episode about the risks associated with driving and the appropriateness of formal driving assessment with the relevant authorities.
B

13.Preventative measures

Avoidance of precipitating factors
Avoid worsening/decompensation of the underlying liver disease, if possible, for the prevention of overt HE.
D
Avoid and manage precipitants, such as infection, constipation, and dehydration, for the prevention of overt HE.
D

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  • Primary prevention

  • Secondary prevention