What is the workup and treatment for decompensated liver failure?

Decompensated Liver Failure: Workup and Treatment

Initial Recognition and Classification

Decompensated cirrhosis requires immediate recognition of whether the patient has acute-on-chronic liver failure (ACLF), as this determines prognosis and urgency of intervention. ACLF is defined by organ failure(s) with 28-day mortality ≥20%, versus <5% in decompensation without ACLF 1.

Diagnostic Criteria for ACLF

Use the CLIF-SOFA scoring system to assess six organ systems 1:

• Liver: Bilirubin >102 mmol/L (>6 mg/dL) indicates failure 1, 2
• Kidney: Creatinine >170 mmol/L or need for renal replacement therapy 1
• Brain: Hepatic encephalopathy grade III-IV 1
• Coagulation: INR ≥2.5 or platelets <10 1
• Circulation: Need for vasopressors (dopamine >5, epinephrine >0.1, norepinephrine >0.1 mcg/kg/min) 1
• Lungs: PaO2/FiO2 <200 or need for mechanical ventilation 1

ACLF grading determines management intensity 1:

• Grade 1: Single organ failure (kidney alone, or liver/coagulation/circulation/lung with creatinine 132-170 mmol/L and/or HE grade 1-2)
• Grade 2: Two organ failures
• Grade 3: Three or more organ failures

Immediate Workup

Essential Laboratory Evaluation

Obtain these tests immediately upon presentation 1, 2:

• Complete metabolic panel: Bilirubin (total and direct), ALT, AST, alkaline phosphatase, albumin, creatinine 2
• Coagulation studies: INR, PT 2
• Complete blood count: To assess for infection, anemia from bleeding 3
• Blood glucose: Check every 2 hours initially, as hypoglycemia mimics encephalopathy 3
• Arterial blood gas: pH and lactate are critical prognostic markers 2
• Ammonia level: If hepatic encephalopathy present 4

Identify Precipitating Factors

Identifying and treating precipitants is the cornerstone of ACLF management 1. Search systematically for:

• Bacterial infection (present in 60-80% of acute liver failure cases): Obtain blood cultures, urine culture, ascitic fluid analysis (cell count, culture, gram stain), chest X-ray 3. Start empirical broad-spectrum antibiotics immediately if sepsis suspected 3.
• Fungal infection (occurs in one-third of acute liver failure patients): Consider if persistent fever despite antibacterials 3
• Gastrointestinal bleeding: Check hemoglobin, perform upper endoscopy if indicated 1
• Viral hepatitis reactivation: HBV DNA, HCV RNA, hepatitis serology 1
• Alcohol-related hepatitis: History of recent heavy drinking, AST:ALT ratio >2:1 1
• Drug-induced liver injury: Detailed medication history including over-the-counter drugs and supplements 1
• Portal vein thrombosis: Doppler ultrasound or CT imaging 1

Etiology-Specific Testing

• Autoimmune hepatitis: ANA, anti-smooth muscle antibody, IgG levels; consider transjugular liver biopsy if severe coagulopathy present 2, 5
• Wilson's disease: Ceruloplasmin, 24-hour urine copper, slit-lamp exam for Kayser-Fleischer rings; look for hemolysis with elevated indirect bilirubin 2
• Hepatitis B: If HBV DNA positive, start nucleos(t)ide analogues (entecavir or tenofovir) immediately—this is an emergency 1, 2

Treatment Strategy

Triage and ICU Admission

All patients with ACLF grade 2-3 require ICU admission 1. Patients with grade 1 ACLF or unstable decompensation need intermediate care with frequent monitoring 2.

Organ Support

Hepatic Encephalopathy Management

• Lactulose: 15-30 mL orally 2-4 times daily, titrate to 2-3 soft bowel movements per day 4
• Rifaximin: 550 mg twice daily (91% of patients in trials used lactulose concomitantly) 6
• Airway protection: Intubate for grade III-IV encephalopathy to prevent aspiration pneumonia 2

Renal Support

• Hepatorenal syndrome: Terlipressin plus albumin is first-line; use norepinephrine if terlipressin unavailable 2
• Avoid excessive volume expansion: Worsens portal hypertension and ascites 2
• Renal replacement therapy: For creatinine >440 mmol/L or refractory fluid overload 1

Circulatory Support

• Vasopressors: For mean arterial pressure <70 mmHg despite fluid resuscitation 1, 2
• Avoid excessive crystalloid: Worsens ascites and portal hypertension 2

Coagulation Management

Do not give prophylactic FFP or platelets—most patients have rebalanced hemostasis 3. Transfuse only for:

• Active bleeding
• High-risk invasive procedures (e.g., transjugular liver biopsy) 3

Prophylactic transfusion obscures disease progression monitoring 3.

Respiratory Support

• Oxygen therapy: Maintain SpO2 >90% 2
• Mechanical ventilation: For PaO2/FiO2 <200 or respiratory distress 1, 2

Infection Management

Empirical broad-spectrum antibiotics are mandatory if infection suspected—do not wait for culture results 3. Bacterial infection is the most common ACLF precipitant 3.

• Start third-generation cephalosporin or piperacillin-tazobactam immediately 3
• Add antifungal coverage if persistent fever after 48-72 hours 3
• Adjust antibiotics based on culture results and local resistance patterns 3

Etiology-Specific Treatments

Hepatitis B Reactivation

Start entecavir or tenofovir immediately—this is an emergency 1, 2. However, 25% of patients deteriorate despite antiviral therapy, so:

• List for transplant evaluation simultaneously 1
• Reassess within 2 weeks: improvement in any lab parameter or stable bilirubin indicates potential response 1

Autoimmune Hepatitis

All decompensated patients should receive a corticosteroid trial before transplant listing 1, 5:

• Prednisone 40-60 mg/day (or 1 mg/kg/day) with or without azathioprine 1, 5
• Assess response at 2 weeks: improvement in bilirubin or any lab parameter predicts success 1, 5
• Poor prognostic signs: multiacinar necrosis on biopsy, bilirubin not improving after 2 weeks—proceed urgently to transplant 1, 5

Wilson's Disease

Urgent transplant evaluation required—medical therapy rarely achieves recovery 2. Consider plasma exchange or albumin dialysis as bridge to transplant 2.

Artificial Liver Support Systems

MARS and Prometheus systems do not improve 28-day or 90-day survival in randomized trials 1. However, they may:

• Improve hepatic encephalopathy and hepatorenal syndrome 1
• Provide short-term bridge to transplant in ACLF grade 2-3 1

Use only in specialized centers as bridge to definitive therapy, not as standalone treatment 1.

Liver Transplantation Evaluation

Early referral to transplant center is critical for ACLF patients 1, 2.

Transplant Candidacy

Immediate transplant evaluation indicated for 1, 2:

• ACLF grade 2-3 2
• King's College criteria met (paracetamol: pH <7.3 or lactate >3.5 mmol/L; non-paracetamol: INR >6.5 or three of: age <10 or >40, non-A/non-B hepatitis, jaundice >7 days before encephalopathy, INR >3.5, bilirubin >17 mg/dL) 2
• Wilson's disease with hemolysis and coagulopathy 2
• Autoimmune hepatitis not responding to corticosteroids after 2 weeks 1, 5

Transplant Outcomes

• 1-year survival: 78% in ACLF patients receiving early transplant vs. <10% without transplant 1
• 5-year survival: 83-92% in adults 1, 5
• Recurrent disease: Occurs in 32% with autoimmune hepatitis but usually mild and manageable 5

Futility Criteria

Consider withdrawal of intensive care if 1:

• Four or more organ failures persist after one week of adequate intensive treatment
• Patient not a transplant candidate
• MELD score >25 with limited transplant access (only 8.6% of trial patients had MELD >19) 6

Prognostic Assessment

Reassess ACLF grade at 3-7 days—trajectory of organ failures predicts outcome better than admission status 1. Improving organ function indicates potential for recovery; worsening or stable multi-organ failure indicates need for urgent transplant 1.

Post-discharge prognosis without transplant is dismal: 1-year survival <25% 1. All survivors should be referred to transplant centers 1.

Critical Pitfalls to Avoid

• Do not delay antibiotics while awaiting cultures—infection drives ACLF progression 3
• Do not give prophylactic blood products—they obscure monitoring and most patients have balanced hemostasis 3
• Do not assume leukopenia requires growth factors—no evidence supports this, and underlying infection must be treated first 3
• Do not delay transplant evaluation in ACLF grade 2-3—the "transplant window" is narrow 1
• Do not continue corticosteroids beyond 2 weeks in autoimmune hepatitis without improvement—proceed to transplant 1, 5
• Do not overlook fungal infections—they occur in one-third of acute liver failure patients 3