What is the management of rising bilirubin in acute decompensated liver failure?

Management of Rising Bilirubin in Acute Decompensated Liver Failure

The management of rising bilirubin in acute decompensated liver failure requires immediate admission to an intensive care unit at a liver transplant center, with early evaluation for liver transplantation as the definitive treatment for eligible patients. 1, 2

Assessment and Classification

• Rising bilirubin is a critical marker of worsening liver function in acute decompensated liver failure, with levels >6 mg/dL indicating liver failure according to the CLIF-Organ Failure score system 1
• Bilirubin levels should be monitored serially to assess disease progression and treatment response, as progressive increases indicate ongoing liver injury and may signal the need for more aggressive interventions 2
• The CLIF-SOFA score evaluates the severity of organ failure, including liver function using bilirubin levels: <20 mmol/L (0 points), >20-34 mmol/L (1 point), >34-102 mmol/L (2 points), >102-204 mmol/L (3 points), and >204 mmol/L (4 points) 2
• Patients should be classified according to the ACLF grading system, with grades determined by the number of organ failures (ACLF I: single organ failure; ACLF II: two organ failures; ACLF III: three or more organ failures) 1

Initial Management

• Patients with rising bilirubin in acute decompensated liver failure should be admitted to intensive care or intermediate care units for close monitoring and management 1, 3
• Early identification and treatment of precipitating factors is crucial, particularly bacterial infections, GI bleeding, drug toxicity, or viral hepatitis reactivation 1, 3
• For patients with ACLF due to HBV reactivation, immediate administration of nucleoside analogues (tenofovir, entecavir) is strongly recommended 1
• Organ function (liver, kidney, brain, lung, coagulation, circulation) should be monitored frequently as ACLF is a dynamic condition 1, 3

Specific Interventions for Hyperbilirubinemia

• Extracorporeal liver support systems such as albumin dialysis (MARS system) or fractionated plasma separation and adsorption (Prometheus system) can be considered for patients with excessive hyperbilirubinemia, although they have not shown significant effects on overall survival in large RCTs 1, 4
• Single-pass albumin dialysis (SPAD) using 2% human serum albumin dialysate has been shown to significantly reduce bilirubin levels (reduction ratio of approximately 23%) in patients with hyperbilirubinemia (total bilirubin > 20 mg/dL) 5
• Bilirubin adsorption therapy can stabilize or decrease bilirubin levels in patients with liver failure and may be a safe short-term treatment option for patients with acute deterioration of hepatic function 4

Supportive Management

• Hemodynamic support: Monitor hemodynamic function and administer vasopressor therapy for marked arterial hypotension; avoid excessive volume expansion 1, 3
• Respiratory support: Provide oxygen therapy and ventilation if respiratory failure is present; special care should be taken to preserve airway patency to prevent aspiration pneumonia 1, 3
• Renal support: If kidney failure is present, identify and manage its cause accordingly; patients meeting criteria for hepatorenal syndrome should be treated with terlipressin and albumin or norepinephrine if terlipressin is unavailable 1, 3
• Hepatic encephalopathy: Treat early with standard therapy to prevent aspiration pneumonia 1
• Coagulation management: For patients with coagulation failure, substitutive therapy should be given only if there is clinically significant bleeding 1

Liver Transplantation Evaluation

• Early referral to liver transplant centers for immediate evaluation is strongly recommended for patients with rising bilirubin and ACLF 1, 2
• Patients with ACLF grade 2-3 according to CLIF-SOFA are candidates for liver transplantation 2
• High bilirubin levels are independently associated with short-term mortality and can be used as a biomarker to improve triage of patients with ACLF 6

Prognostic Considerations

• Bilirubin levels are a significant predictor of short-term mortality in ACLF patients, with higher levels associated with worse outcomes 6
• In patients who are not candidates for liver transplantation with four or more organ failures after one week of adequate intensive treatment, withdrawal of intensive care support can be considered due to futility 1
• The MELD score (which includes bilirubin) and the stage of hepatic encephalopathy are highly associated with mortality in ACLF patients 7

Special Considerations

• In Wilson's disease presenting as ALF, bilirubin is typically markedly elevated with a predominant indirect fraction due to hemolysis; treatment should include plasma exchange or albumin dialysis to lower serum copper, but recovery is infrequent without transplantation 1, 2
• In autoimmune hepatitis causing ALF, liver biopsy (preferably via the transjugular route in the presence of severe coagulopathy) may be necessary for diagnosis, and corticosteroid therapy (prednisone 40-60 mg/day) should be initiated while placing the patient on the transplant list 1, 2
• In drug-induced liver injury causing acute decompensation, bilirubin >2x ULN along with ALT >3x ULN and ALP >2x ULN is diagnostic 2

Pitfalls and Caveats

• Isolated hyperbilirubinemia may be due to Gilbert's syndrome or hemolysis rather than worsening liver function 2
• Bilirubin may be falsely elevated in patients with hemolysis, which should be excluded when evaluating acute liver failure 2
• In ischemic hepatitis, serum bilirubin is usually <3 mg/dL despite marked elevations in transaminases and coagulopathy 2
• Bilirubin levels should always be interpreted in the context of other liver function tests and clinical parameters 2