Treatment of High Bilirubin in Adults with Cirrhosis
The primary treatment for hyperbilirubinemia in adults with cirrhosis should focus on managing the underlying liver disease and its complications, with specific interventions including sodium restriction, diuretic therapy, and albumin infusion for severe cases.
Understanding Hyperbilirubinemia in Cirrhosis
Hyperbilirubinemia in cirrhosis is typically a manifestation of progressive liver dysfunction and can be exacerbated by:
- Worsening of underlying liver disease
- Development of complications (ascites, hepatorenal syndrome)
- Superimposed acute liver injury
- Medication effects
First-Line Management Approach
1. Address the Underlying Liver Disease
- Identify and treat the primary cause of cirrhosis:
- Abstinence from alcohol for alcoholic liver disease
- Antiviral therapy for viral hepatitis
- Weight loss and metabolic control for non-alcoholic fatty liver disease
- Avoid hepatotoxic medications that may worsen hyperbilirubinemia 1
2. Dietary and Fluid Management
- Sodium restriction (5-6.5g salt/day or 87-113 mmol sodium/day) 1
- Adequate caloric intake (35-40 kcal/kg/day) and protein (1.2-1.5 g/kg/day) 1
- Fluid restriction is generally not necessary except in cases of severe hyponatremia (serum sodium <120-125 mmol/L) 2
3. Management of Ascites
Ascites management is crucial as it often accompanies hyperbilirubinemia in advanced cirrhosis:
| Grade | Description | Treatment |
|---|---|---|
| Grade 1 (mild) | Only detectable by ultrasound | Sodium restriction |
| Grade 2 (moderate) | Moderate abdominal distension | Sodium restriction + Diuretics |
| Grade 3 (large) | Marked abdominal distension | Sodium restriction + Diuretics + Paracentesis |
- For Grade 2 ascites: Start with spironolactone 100 mg daily, which can be increased up to 400 mg/day 1
- For recurrent ascites: Combination therapy with spironolactone 100 mg + furosemide 40 mg daily 1
- For Grade 3 ascites: Large volume paracentesis with albumin replacement (8g albumin per liter of ascites removed for paracentesis >5L) 1
Advanced Interventions for Severe Hyperbilirubinemia
1. Albumin Infusion
- For patients with severe hyperbilirubinemia and decompensated cirrhosis, albumin infusion (25g/week) may improve diuretic responsiveness and reduce hospital readmissions 2
- Long-term albumin administration (25g/week up to 1 year, then 25g every 2 weeks) after first-onset ascites has been shown to improve survival and decrease ascites recurrence 2
2. Extracorporeal Albumin Dialysis (ECAD)
- For patients with cirrhosis and superimposed acute injury with progressive hyperbilirubinemia (>20 mg/dL), ECAD has shown improved 30-day survival compared to standard medical therapy 3
- ECAD can decrease plasma bile acids and bilirubin by approximately 43% and 29%, respectively, after one week of treatment 3
- This approach may be particularly useful for increasing survival in patients awaiting liver transplantation 3
3. Bilirubin Adsorption (BA)
- For excessive hyperbilirubinemia (>25 mg/dL), bilirubin adsorption can stabilize or decrease bilirubin levels 4
- A single BA treatment can reduce bilirubin levels from an average of 31 mg/dL to 23.7 mg/dL 4
- This is a short-term treatment option for patients with acute deterioration of hepatic function 4
Management of Complications
1. Spontaneous Bacterial Peritonitis (SBP)
- Diagnostic paracentesis should be performed if ascites is present 1
- SBP is diagnosed with neutrophil count >250/mm³ in ascitic fluid 1
- Immediate treatment with third-generation cephalosporins (e.g., ceftriaxone) 1
2. Hepatorenal Syndrome
- Avoid nephrotoxic drugs (NSAIDs, aminoglycosides, ACE inhibitors, ARBs) 1
- For type I hepatorenal syndrome, consider albumin infusion plus vasoactive drugs (octreotide and midodrine) 2
3. Hepatic Encephalopathy
- Lactulose as first-line therapy 1, 5
- Avoid sedatives and medications that may precipitate encephalopathy 1
- Consider branched-chain amino acid supplementation 1
Liver Transplantation Evaluation
- Referral for liver transplantation evaluation should be considered for patients with persistent hyperbilirubinemia despite medical management 1
- Liver transplantation remains the only curative option for end-stage liver disease 1
- Patients with cirrhosis, ascites, and type I hepatorenal syndrome should have an expedited referral for liver transplantation 2
Monitoring
- Regular monitoring of liver function tests, electrolytes, and renal function
- Ultrasound screening for hepatocellular carcinoma every 6 months
- Endoscopic surveillance for varices
Caution
- Protease inhibitors (including simeprevir) should be used with extreme caution, if at all, in patients with advanced cirrhosis as they may cause marked hyperbilirubinemia and hepatic decompensation 6
- Endoscopic procedures like variceal ligation may potentially worsen hyperbilirubinemia in some patients with advanced cirrhosis 7