What test has the greatest prognostic value in a patient with liver disease, as indicated by elevated total bilirubin (hyperbilirubinemia), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels?

Prothrombin Time Has the Greatest Prognostic Value in Acute Liver Injury

In this patient with acute hepatocellular injury (markedly elevated transaminases with jaundice), prothrombin time is the single most important prognostic marker as it directly reflects hepatic synthetic function and predicts mortality, hepatic encephalopathy, and need for transplantation. The answer is C. Prothrombin time.

Why Prothrombin Time is Superior for Prognosis

Prothrombin time directly measures the liver's ability to synthesize clotting factors and is the most dynamic indicator of hepatic synthetic function in acute injury. 1 This is fundamentally different from the other markers:

• PT/INR is the core component of all major prognostic scoring systems including the Maddrey Discriminant Function (MDF), MELD score, and Child-Pugh score, which predict survival in acute and chronic liver disease 2, 1
• PT prolongation (INR >1.5) combined with altered mental status defines acute liver failure and predicts need for liver transplantation 1
• Serial PT monitoring tracks disease progression in real-time, with worsening PT at 48-72 hours despite treatment indicating poor prognosis and need for escalation of care 1

Why the Other Options Are Inferior

Bilirubin (Option A)

While bilirubin reflects overall liver function, it is less dynamic and clinically relevant than PT for acute prognostication 1. Bilirubin can remain elevated due to delta bilirubin (21-day half-life) even after the underlying injury resolves, making it a lagging indicator 3. In the Maddrey Discriminant Function, PT carries more weight (coefficient of 4.6) than bilirubin (coefficient of 1.0) 2.

Albumin (Option B)

Albumin has a half-life of approximately 20 days, making it useful for chronic liver disease assessment but too slow to reflect acute changes in hepatic synthetic function 4, 5. In this patient with only 7 days of symptoms, albumin would not yet reflect the severity of acute injury.

ALT (Option D)

While ALT indicates the degree of hepatocellular injury occurring day-by-day, it does not predict prognosis or mortality 4, 5. Transaminases can be markedly elevated (as in this case with ALT 1650) yet the patient may recover fully if synthetic function (PT) remains intact. Conversely, patients can have modest transaminase elevations but develop fulminant hepatic failure if PT becomes severely prolonged.

Clinical Application in This Case

For this patient presenting with:

• Markedly elevated transaminases (AST 700, ALT 1650) indicating severe acute hepatocellular injury
• Elevated bilirubin (26 μmol/L) indicating impaired hepatic function
• 7-day symptom duration requiring assessment of synthetic function

The immediate priority is measuring PT/INR to assess hepatic synthetic capacity and stratify mortality risk 1:

• INR >1.5 with hepatic encephalopathy defines acute liver failure and warrants immediate transplant evaluation 1
• INR >2.0 predicts high mortality risk regardless of encephalopathy status 1
• Serial PT measurements (daily or more frequently) should be obtained to track disease trajectory 1

Critical Prognostic Thresholds

The most important PT/INR cutoffs for risk stratification are 2, 1:

• INR ≥1.5: Defines coagulopathy; combined with encephalopathy = acute liver failure
• INR ≥2.0: High mortality risk; consider transplant evaluation
• Maddrey Discriminant Function ≥32: 30-50% one-month mortality (MDF = 4.6 × [PT - control PT] + bilirubin in mg/dL)
• MELD score ≥18: Poor prognosis in acute alcoholic hepatitis

Common Pitfalls to Avoid

• Do not rely solely on transaminase levels to gauge prognosis - patients with massive transaminase elevations (>1000) can have excellent outcomes if PT remains normal 4
• Do not wait for albumin to decline before assessing severity - albumin changes too slowly to guide acute management 5
• Check vitamin K status in cholestatic patients - fat-soluble vitamin deficiency can cause elevated INR that mimics liver dysfunction rather than true synthetic failure 3
• Recognize that worsening PT despite treatment is ominous - failure of PT to improve or continued prolongation at 48-72 hours predicts poor outcome and need for transplant evaluation 1