What is the management approach for a patient with acute on chronic liver failure, presenting with signs of severe liver dysfunction, such as hepatic encephalopathy, variceal bleeding, or impaired renal function?

Management of Acute-on-Chronic Liver Failure

Immediately admit all ACLF patients with signs of severe liver dysfunction to the ICU for aggressive organ support, rapid identification and treatment of precipitating events, and urgent liver transplant evaluation, as mortality is exceedingly high but organ dysfunction is often reversible. 1, 2

Initial Assessment and Diagnostic Workup

Rapidly identify the precipitating event through targeted investigations:

• Obtain blood cultures, urinalysis with culture, chest X-ray, complete blood count with differential, and C-reactive protein to identify infections 2, 3
• Perform diagnostic paracentesis if ascites is present to rule out spontaneous bacterial peritonitis (SBP) 2, 3
• Measure serum acetaminophen levels regardless of history, as acetaminophen toxicity may be occult 2, 4
• Check hepatitis A IgM and hepatitis B serologies (HBsAg, anti-HBc IgM) 2, 4
• Obtain hepatic Doppler ultrasound to verify vessel permeability and exclude portal vein thrombosis or Budd-Chiari syndrome 1, 3
• Perform echocardiography to assess for cirrhotic cardiomyopathy and guide hemodynamic management 1, 3

Management of Hepatic Encephalopathy

Critical distinction: Do NOT use lactulose or rifaximin in ACLF patients with hepatic encephalopathy, as these agents are only indicated for chronic stable cirrhosis, not acute decompensation. 2

Instead, implement the following approach:

• Intubate and sedate when Glasgow Coma Score falls below 8 or with progressive grade III-IV encephalopathy to protect the airway 1, 2
• Maintain serum sodium between 140-145 mmol/L to prevent cerebral edema 1, 2
• Monitor blood glucose at least every 2 hours and correct hypoglycemia aggressively 2, 3
• Consider nonabsorbable disaccharides (conditional recommendation, low quality evidence) or enteral polyethylene glycol as an alternative 1
• Consider oral rifaximin as adjunctive therapy only (conditional recommendation, low quality evidence) 1
• Avoid benzodiazepines and psychotropic drugs like metoclopramide that worsen encephalopathy 1, 3

The 2023 Critical Care Medicine guidelines suggest using L-ornithine L-aspartate (LOLA) in critically ill ACLF patients with overt hepatic encephalopathy, though this is based on very low quality evidence. 1

Management of Variceal Bleeding

Implement a multimodal approach combining pharmacologic, endoscopic, and antibiotic therapy:

• Start octreotide or somatostatin analog immediately for portal hypertensive bleeding (strong recommendation, moderate quality evidence) 1
• Administer proton pump inhibitors (strong recommendation, low quality evidence) 1
• Use antibiotic prophylaxis for any type of upper gastrointestinal bleeding (strong recommendation, moderate quality evidence) 1
• Perform endoscopic intervention with variceal band ligation or sclerotherapy 1
• Consider transjugular intrahepatic portosystemic shunt (TIPS) for recurrent variceal bleeding after medical and endoscopic intervention failure (conditional recommendation, low quality evidence) 1

Avoid routine correction of coagulation parameters unless active bleeding is present, as INR elevation reflects synthetic dysfunction rather than bleeding risk in cirrhosis. 1, 3

Management of Spontaneous Bacterial Peritonitis and Sepsis

Administer broad-spectrum antibiotics immediately upon recognition:

• Use broad-spectrum antibiotic agents for initial management of SBP (strong recommendation, low quality evidence) 1
• Administer appropriate antibiotics as soon as possible and within 1 hour of shock onset in patients with SBP and septic shock (conditional recommendation, low quality evidence) 1
• Add albumin infusion in critically ill ACLF patients with SBP (strong recommendation, moderate quality evidence) 1
• Do NOT perform large volume paracentesis in patients with SBP (conditional recommendation, very low quality evidence) 1
• Do NOT use midodrine or terlipressin for ACLF patients with SBP (conditional recommendation, very low quality evidence) 1

Management of Renal Dysfunction

Implement renal-protective strategies and provide renal replacement therapy when indicated:

• Avoid nephrotoxic drugs including NSAIDs 1, 3
• Use balanced (normochloremic) crystalloid solutions over normal saline for fluid replacement (conditional recommendation, low quality evidence) 1
• Provide continuous renal replacement therapy (CRRT) rather than intermittent hemodialysis for acute kidney injury 3
• Assess volume status, cardiac output, and biventricular cardiac function to guide fluid management 3
• Use norepinephrine for refractory hypotension to maintain mean arterial pressure ≥50-60 mmHg 3

Management of Ascites and Intra-abdominal Hypertension

Perform large volume paracentesis with albumin replacement for tense ascites:

• Perform LVP with measurement of intra-abdominal pressure in critically ill ACLF patients with tense ascites and intra-abdominal hypertension or hemodynamic, renal, or respiratory compromise (best practice statement) 1
• Administer albumin over crystalloid for volume replacement during paracentesis 1

Respiratory Management

Implement lung-protective ventilation strategies:

• Use standard lung-protective ventilation with low tidal volumes (6-8 mL/kg predicted body weight) and plateau pressures <30 cm H2O 3
• Intubate early for progressive encephalopathy or respiratory failure 1, 2

Nutritional Support

Initiate early enteral nutrition:

• Provide early enteral nutrition with moderate protein intake (approximately 60 grams per day) 4
• Do not restrict protein in ACLF patients with encephalopathy, as this worsens outcomes 4

N-Acetylcysteine Administration

Administer N-acetylcysteine systematically regardless of etiology:

• Initiate N-acetylcysteine therapy in all patients with acute liver failure, whatever the etiology, to improve morbidity and mortality (GRADE 2+, strong agreement) 1, 4, 3
• This applies even when acetaminophen is not the suspected cause 1, 4

Liver Transplant Evaluation

Contact a transplant center immediately for all ACLF patients:

• Early referral to specialist liver centers is essential, as the "transplantation window" is often narrow 2, 4
• Poor prognostic indicators requiring urgent transplant consideration include idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, Budd-Chiari syndrome, or indeterminate cause 2, 3
• Post-transplant survival rates are 80-90% when appropriately selected 4

Infection Prophylaxis and Surveillance

Maintain high vigilance for infectious complications:

• Use systemic antifungal prophylaxis in critically ill liver transplant recipients with risk factors for invasive fungal infections (conditional recommendation, very low quality evidence) 1
• Do NOT use selective bowel decontamination for critically ill liver transplant recipients (conditional recommendation, low quality evidence) 1
• Administer empirical broad-spectrum antibiotics for worsening hepatic encephalopathy or signs of systemic inflammatory response syndrome 3

Common Pitfalls to Avoid

Key errors that worsen outcomes in ACLF:

• Using lactulose or rifaximin for hepatic encephalopathy in acute decompensation (these are only for chronic stable cirrhosis) 2
• Routinely correcting INR with fresh frozen plasma in the absence of active bleeding 1, 3
• Using nephrotoxic agents including NSAIDs 1, 3
• Delaying transplant evaluation until the patient is "too sick" 2, 4
• Using normal saline instead of balanced crystalloids for resuscitation 1