What is the difference between albumin and bilirubin when assessing liver function?

Albumin vs. Bilirubin in Liver Function Assessment

Core Distinction

Albumin and bilirubin measure fundamentally different aspects of liver function: albumin reflects hepatic synthetic capacity (the liver's ability to produce proteins), while bilirubin reflects hepatic excretory function (the liver's ability to process and eliminate waste products). 1, 2

Albumin: Marker of Synthetic Function

What it measures:

• Albumin is produced exclusively by the liver and serves as the primary indicator of the liver's protein synthesis capacity 2
• Normal values: >3.5 g/dL; levels <3.5 g/dL indicate impaired hepatic synthetic function 2
• Half-life of approximately 20 days, making it a marker of chronic rather than acute liver dysfunction 3

Clinical significance:

• Low albumin is the most concerning finding when assessing liver function, as it indicates loss of hepatic reserve 2
• Incorporated into both Child-Pugh scoring (along with bilirubin, PT, ascites, encephalopathy) and the ALBI score (albumin-bilirubin grade) for prognostic stratification 1
• The ALBI score can further stratify Child-Pugh A patients into ALBI grade 1 (better prognosis) versus ALBI grade 2 (worse prognosis), with median survivals of 26 versus 14 months respectively 1

Critical limitation:

• Albumin is NOT liver-specific and can be reduced in numerous non-hepatic conditions including sepsis, systemic inflammatory disorders, nephrotic syndrome, malabsorption, gastrointestinal protein loss, and malnutrition 2, 4
• Overinterpretation of low albumin as definitive evidence of liver disease is a common pitfall 2, 4

Bilirubin: Marker of Excretory Function

What it measures:

• Bilirubin reflects the liver's ability to conjugate and excrete bile pigments, representing overall hepatic metabolic clearance 5
• Normal total bilirubin: <1.2 mg/dL; direct (conjugated) bilirubin: <0.18 mg/dL 2
• Bilirubin is considered "probably the best test of overall liver function" among routine laboratory tests 5

Clinical significance:

• Elevated bilirubin indicates impaired hepatic excretion and is incorporated into Child-Pugh, MELD, and ALBI scoring systems 1
• Pattern analysis is critical: conjugated hyperbilirubinemia (direct >35% of total) suggests cholestatic disease or biliary obstruction, while unconjugated elevation suggests hemolysis or Gilbert's syndrome 2, 6
• Normal bilirubin with only minimally elevated direct fraction argues against significant cholestatic disease 2

Prognostic value:

• Elevated bilirubin predicts poor outcomes including tumor recurrence after resection, drop-out from transplant waiting lists, and reduced survival in advanced HCC 1
• The combination of albumin and bilirubin (ALBI score) has proven remarkably accurate for prognosis across multiple liver diseases and even non-hepatic conditions 7

Integrated Assessment Framework

When evaluating liver function, both parameters must be interpreted together:

• Compensated cirrhosis (Child-Pugh A): Normal or near-normal albumin (>3.5 g/dL) and bilirubin (<2 mg/dL) 1
• Decompensated cirrhosis (Child-Pugh B/C): Progressive decline in albumin and/or elevation in bilirubin, along with clinical signs (ascites, encephalopathy) 1
• Low albumin with normal bilirubin and normal aminotransferases: Consider non-hepatic causes first (nephrotic syndrome, malnutrition, protein-losing enteropathy, systemic inflammation) before attributing to chronic stable liver disease 2, 4

Essential complementary tests:

• Prothrombin time/INR (another synthetic function marker) 1
• Aminotransferases (ALT/AST) to assess active hepatocellular injury 1, 4
• Platelet count and imaging for portal hypertension assessment 1

Clinical Decision-Making Algorithm

For newly identified liver lesions with abnormal liver function tests: 2

1. If albumin is low (<3.5 g/dL) but bilirubin is normal:

   • Rule out non-hepatic causes (urinalysis for proteinuria, nutritional assessment, inflammatory markers)
   • Check PT/INR to confirm synthetic dysfunction
   • If PT/INR also abnormal → chronic liver disease with impaired synthetic function

2. If bilirubin is elevated (>1.2 mg/dL):

   • Determine if conjugated (direct >35% of total) or unconjugated
   • Conjugated → abdominal ultrasound to distinguish intrahepatic cholestasis from biliary obstruction 4
   • Unconjugated → evaluate for hemolysis or Gilbert's syndrome 2

3. If both albumin and bilirubin are abnormal:

   • Calculate Child-Pugh score and ALBI grade for prognostic stratification 1
   • Assess for signs of portal hypertension (varices, splenomegaly, thrombocytopenia <100×10⁹/L) 1
   • Consider MELD score if transplant evaluation is relevant 1

The key pitfall to avoid: Never assume normal albumin and bilirubin exclude significant liver disease—30% of patients with cirrhosis may have normal routine liver function tests until complications develop 4