A patient with hemoglobin 187 g/L, AST approximately 500 U/L, ALT approximately 90 U/L, total bilirubin 5.7 mg/dL (direct 3.9 mg/dL) – what is the appropriate next step in management?

Acute Hepatocellular Injury with Conjugated Hyperbilirubinemia: Immediate Diagnostic Workup Required

This patient presents with severe hepatocellular injury (AST 493 U/L, ALT 88 U/L) and conjugated hyperbilirubinemia (direct bilirubin 3.9 mg/dL, 68% of total), indicating acute liver damage that requires urgent evaluation to identify the underlying cause and assess for potential acute liver failure. 1, 2

Immediate Assessment (Within 24 Hours)

Critical Laboratory Tests

• Obtain INR/PT and albumin immediately to assess synthetic liver function and determine if this represents acute liver failure 1, 2
• Check complete blood count with peripheral smear to evaluate for hemolysis (which can elevate indirect bilirubin) and assess platelet count as a marker of portal hypertension 1, 2
• Measure lactate dehydrogenase (LDH) because the markedly elevated AST with relatively lower ALT suggests possible ischemic hepatitis; an ALT/LDH ratio <1.5 has 94% sensitivity for distinguishing ischemic injury from viral hepatitis 3
• Order viral hepatitis serologies (HBsAg, anti-HBc IgM, anti-HCV, anti-HAV IgM, anti-HEV IgM) as superimposed viral hepatitis commonly causes AST/ALT >400 U/L with bilirubin >3 mg/dL 1, 4

Imaging

• Obtain abdominal ultrasound within 24-48 hours to exclude biliary obstruction (sensitivity 65-95%) and evaluate for structural liver disease 2, 4
• Ultrasound should specifically assess for bile duct dilation, focal liver lesions, ascites, and portal vein patency 2

Pattern Recognition: AST-Predominant Injury

The AST:ALT Ratio >5 Narrows the Differential

• This AST:ALT ratio of 5.6:1 is highly unusual and suggests specific etiologies rather than common causes like NAFLD or viral hepatitis (which typically show AST:ALT <1) 4, 5
• Ischemic hepatitis is the most likely diagnosis given the marked AST predominance; it typically presents with AST/ALT >400 U/L, bilirubin usually <5 mg/dL, and profound coagulopathy that improves rapidly 1
• Alcoholic hepatitis characteristically shows AST:ALT ratio >2 (often 2-6:1), but AST rarely exceeds 400-500 U/L and this patient's AST of 493 U/L with such low ALT is more consistent with ischemic injury 1, 4
• Wilson disease with acute liver failure presents with modest transaminase elevations, Coombs-negative hemolysis, and alkaline phosphatase:bilirubin ratio <4, but typically affects patients <40 years 1

Assess for Ischemic Hepatitis

• Evaluate for recent hypotension, cardiac arrest, severe heart failure, or shock as ischemic hepatitis requires a precipitating hemodynamic event 1
• Order echocardiography to evaluate right and left ventricular function if ischemic hepatitis is suspected 1
• Confirm vascular patency with Doppler ultrasound to exclude hepatic vein thrombosis or portal vein thrombosis 1

Medication Review and Drug-Induced Liver Injury

• Review all medications, over-the-counter drugs, and herbal supplements against the LiverTox® database, as drug-induced liver injury causes 8-11% of cases with elevated transaminases 6, 4
• Acetaminophen toxicity must be excluded urgently; obtain acetaminophen level even if no history of ingestion, as it can present with AST >ALT and conjugated hyperbilirubinemia 7, 6
• If acetaminophen level is elevated or unavailable and clinical suspicion exists, initiate N-acetylcysteine immediately as efficacy diminishes after 8 hours post-ingestion 7

Autoimmune and Metabolic Causes

• Check autoimmune markers (ANA, anti-smooth muscle antibody, IgG levels) as autoimmune hepatitis can present with acute hepatocellular injury, though it typically shows higher ALT elevations 1, 4
• Obtain ceruloplasmin and 24-hour urinary copper if patient is <40 years old to exclude Wilson disease, which can present with acute liver failure 1
• Screen for hemochromatosis with ferritin and transferrin saturation, though this rarely presents acutely 4

Monitoring Strategy

If Synthetic Function Is Preserved (Normal INR, Albumin >3.5 g/dL)

• Repeat liver enzymes, bilirubin, and INR within 2-3 days to establish trend 2, 5
• If ALT increases to >300 U/L or bilirubin continues rising, escalate to daily monitoring and consider hepatology consultation 2, 5

If Synthetic Function Is Impaired (INR >1.5, Albumin <3.0 g/dL)

• This represents acute liver failure requiring immediate hepatology referral and consideration of transfer to a transplant center 1
• Monitor for hepatic encephalopathy, coagulopathy, and renal dysfunction as these indicate progression to acute-on-chronic liver failure 1

Critical Pitfalls to Avoid

• Do not assume this is simple alcoholic liver disease based on AST:ALT ratio alone; the absolute AST level of 493 U/L with such marked AST predominance is more consistent with ischemic injury 1, 3
• Do not delay imaging because the conjugated hyperbilirubinemia (68% direct) mandates exclusion of biliary obstruction within 24-48 hours 2, 4
• Do not overlook acetaminophen toxicity even without a clear ingestion history, as it is a leading cause of acute liver failure and requires immediate antidote therapy 7, 6
• Do not attribute prolonged INR to liver dysfunction before checking vitamin K status, as fat-soluble vitamin deficiencies are common in cholestatic disease 2
• Do not miss ischemic hepatitis by failing to assess recent hemodynamic events; this diagnosis requires correlation with cardiac function and recent hypotensive episodes 1, 3

Immediate Next Steps Summary

1. Order INR, albumin, CBC, LDH, and acetaminophen level stat 1, 2, 7, 3
2. Obtain viral hepatitis serologies and abdominal ultrasound within 24 hours 1, 2, 4
3. Review all medications and assess for recent hypotension or cardiac events 1, 6, 4
4. If INR >1.5 or encephalopathy develops, arrange immediate hepatology consultation 1
5. Repeat liver panel in 2-3 days to establish trend 2, 5