Bilirubin as a Prognostic Indicator of Liver Failure
Bilirubin is a strong and reliable prognostic indicator of liver failure, with elevated levels consistently associated with poor outcomes and increased mortality risk across various liver disease presentations.
Bilirubin in Acute Liver Failure
Bilirubin serves as a key component in the diagnosis and prognostication of acute liver failure:
The American Association for the Study of Liver Diseases defines acute liver failure as the presence of coagulopathy, hepatic encephalopathy, and absence of pre-existing liver disease, with elevated bilirubin (>3 mg/dL) being a characteristic feature 1
In acute liver failure, the pattern and degree of bilirubin elevation helps distinguish between different etiologies:
Bilirubin in Chronic Liver Disease and Cirrhosis
In chronic liver disease, bilirubin elevation reflects disease progression:
Serum bilirubin has been shown to be a strong marker of prognosis in chronic cholestatic diseases, but it typically rises permanently above the upper limit of normal only in late-stage disease 2
In advanced cirrhosis, glucuronyl conjugation of bilirubin and biliary excretion of conjugated bilirubin become markedly impaired, leading to jaundice. The concentration of bilirubin in serum thus becomes a good prognostic marker for patients with decompensated liver cirrhosis 3
Bilirubin in Acute-on-Chronic Liver Failure (ACLF)
Bilirubin is particularly valuable as a prognostic marker in ACLF:
High levels of bilirubin are able to predict short-term mortality in patients with ACLF. In ROC curve analysis, conjugated (0.751, p < 0.05) and total bilirubin (0.746, p < 0.05) levels were significantly the best short-term mortality predictors 4
Recent research has established that admission bilirubin >7.5 mg/dl is a cutoff associated with increased mortality risk in cirrhosis patients, and can be used to identify liver failure when combined with INR >1.5 5
The direct bilirubin to total bilirubin ratio (DB/TB) has prognostic significance in ACLF. Patients with DB/TB ≥0.80 had much lower 90-day mortality risk compared to those with DB/TB <0.80 6
Bilirubin in Specific Liver Diseases
Primary Biliary Cholangitis (PBC)
- Referral for liver transplantation should be made once the serum bilirubin exceeds 100 μmol/l or significant impairment of liver function ensues 2
Wilson's Disease
- In fulminant Wilson's disease, bilirubin levels are typically >10 mg/dL with a characteristic pattern including:
- Coombs-negative hemolytic anemia
- Low alkaline phosphatase
- A high bilirubin (mg/dL) to alkaline phosphatase (IU/L) ratio (≥2.0) is a reliable indicator of Wilson disease 2
Clinical Application and Pitfalls
When to Use Bilirubin for Prognosis
- Bilirubin should be evaluated in conjunction with other markers of liver dysfunction, particularly:
- Coagulation parameters (INR, factor V)
- Presence of hepatic encephalopathy
- Renal function
Common Pitfalls
Isolated unconjugated hyperbilirubinemia may not reflect liver failure but rather conditions like Gilbert's syndrome or hemolysis 7
In some conditions like ischemic hepatitis, bilirubin may remain relatively low despite severe liver injury 2
Bilirubin naturally fluctuates in some conditions like primary sclerosing cholangitis, which may complicate its use as a standalone prognostic marker 2
Conclusion
Bilirubin is a powerful prognostic indicator in liver failure across various etiologies. Its utility is maximized when interpreted in the context of other clinical and laboratory parameters, particularly INR, creatinine, and the presence of hepatic encephalopathy. Recent research has established specific cutoff values (such as >7.5 mg/dL) that are strongly associated with increased mortality risk, making bilirubin an essential component of prognostic models in liver failure.