Hepatic Encephalopathy Overview

Early Anti-Infection Treatments

• Introduce early anti-infection treatments when hepatic encephalopathy progresses, infections appear, or SIRS is present.
• Consider antifungal therapy for patients with prolonged critical care and multiple organ failure.

Hepatic Encephalopathy (HE)

• Fluctuating condition; can progress from mild awareness loss to deep coma.
• Associated symptoms include headache, vomiting, asterixis, agitation, hyperreflexia, and clonus.
• HE diagnosis is made through exclusion of other conditions.
• HE progression mirrors liver function deterioration.
• Neurological deterioration can be worsened by infection or inflammation, even without sepsis, or other organ failure.

Progression to Grade 3 HE

• Characterized by agitation, frequent aggression and decreased Glasgow Coma Scale (GCS) score (typically E1-2, V3-4, M4).
• Intubation, mechanical ventilation, and aspiration prevention are recommended to improve respiratory care.

Progression to Grade 4 HE

• Severe condition with notably decreased GCS (E1, V1-2, M1-3).
• Risk reduction of pulmonary barotrauma is essential.
• Target PaCO2 is 4.5-5.5 kPa (34-42 mmHg).
• Propofol is the recommended sedative.
• Anti-seizure drugs (e.g. levetiracetam or lacosamide) may be used to protect from ICH, but are not routinely warranted.
• Opiod use, for adequate pain management, is essential.
• Monitor EEG if seizure risk is high.
• Administer antiepileptic drugs with minimal hepatotoxicity risk.
• Frequent clinical and neurological evaluations are required.

Liver Transplantation

• Transplantation is indicated for patients with irreversible acute liver failure (ALF).
• Survival following emergency liver transplant can be as high as 80%.
• Selection for transplant depends on the patient's predicted survival without transplant, their potential for survival after transplant, and if they are too sick to allow transplant procedures.

Criteria for Emergency Liver Transplantation

• King's Criteria: pH <7.3, lactate >3mmol/L, or Grade 3 HE, serum creatinine >300 µmol/L, and INR >6.5.
• Beaujon-Paul Brousse Criteria: confusion/coma (HE grades 3 or 4), Factor V <20% if <30 years, Factor V <30% if >30 years, INR ≥6.5, or 3/5 of: aetiology, age, interval jaundice encephalopathy >7 days, bilirubin ≥300 µmol/L, INR ≥3.5

Organ-Specific Management in ALF

• Main complications:
  • Coagulation/haemostasis
  • Neurological (cerebral oedema)
  • Infection
  • Pulmonary
  • Metabolic
  • Renal
• Regular monitoring of organ function (e.g. renal, pulmonary).
• Clinical decision-making regarding organ support/treatment is mandatory.

Transfer to Specialized Unit

• Transfer to specialized units is crucial.
• Early transfer to specialized units improves outcomes.
• Consider transfer when hepatic encephalopathy, renal dysfunction, non-specific features, or poor prognostic signs appear.
• Suggested referral criteria for ALF exist.

Other Relevant Assessments

• Acute kidney injury (AKI) is common, and renal replacement therapy (RRT) might be necessary.
• Coagulation abnormalities (thrombocytopenia, reduced coagulation factors) are common.
• Sepsis, inflammation and anti-inflammatory management is crucial.
• Regular blood tests for monitoring and adjusting treatment strategies are required.
• Liver transplantation is the most effective solution when indicated.

Pregnancy-Related ALF

• If ALF occurs in pregnancy, interventions targeting the baby are a priority.

Differential Diagnoses of ALF

• Paracetamol overdose is a common cause.
• Other causes include viral hepatitis, drug reactions, acute Budd-Chiari syndrome, Wilson's disease, and mushroom poisoning.

Classification of ALF

• ALF is classified based on the duration between jaundice onset and HE development (hyperacute, acute, subacute).
• Different classifications evaluate the severity and prognosis of the patient.

Assessment and Management at Presentation

• Immediate actions
• Exclude other conditions
• Initiate early discussion with a transplant centre.
• Screen for HE
• Determine the aetiology.