What is the initial work-up for a patient presenting with jaundice and an Aspartate Aminotransferase (AST) to Alanine Aminotransferase (ALT) ratio of 1.47?

Work-up for Jaundice with AST:ALT Ratio of 1.47

In a patient presenting with jaundice and an AST:ALT ratio of 1.47, the most likely diagnosis is alcoholic hepatitis, and the initial work-up should prioritize confirming heavy alcohol use (>40-60 g/day for >6 months with <60 days abstinence), obtaining a complete liver panel with bilirubin >3 mg/dL, and excluding biliary obstruction with imaging while testing for alternative diagnoses. 1

Understanding the AST:ALT Ratio

The AST:ALT ratio of 1.47 is highly suggestive of specific etiologies:

• An AST:ALT ratio >1.5 is characteristic of alcoholic hepatitis, with <2% of histologically proven alcoholic hepatitis cases showing ratios <1.5 1
• In alcoholic liver disease, the AST:ALT ratio is typically >2.0, though ratios between 1.5-2.0 remain highly suggestive when combined with appropriate clinical context 1, 2
• This ratio pattern distinguishes alcoholic liver disease from other causes: chronic viral hepatitis and NAFLD typically show AST:ALT ratios <1.0 3, 2
• An AST:ALT ratio >1.0 in nonalcoholic liver disease suggests underlying cirrhosis, with mean ratios rising from 0.59 without cirrhosis to 1.02 with cirrhosis in chronic hepatitis B 2

Essential Initial Laboratory Testing

Complete Liver Panel

• Measure serum bilirubin (expect >3 mg/dL or >50 μmol/L in alcoholic hepatitis), AST (expect >50 IU/mL but rarely >400 IU/mL), ALT, alkaline phosphatase, albumin, and prothrombin time/INR 1
• AST and ALT typically do not exceed 400 IU/mL in alcoholic hepatitis, distinguishing it from drug-induced liver injury and ischemic hepatitis 1
• Check for neutrophilia, which is frequently observed in alcoholic hepatitis 1

Exclude Alternative Diagnoses

• Viral hepatitis serologies: HBsAg, anti-HBc IgM, HCV antibody, and HAV IgM to exclude viral causes 4
• Autoimmune markers: ANA, anti-smooth muscle antibodies, and serum IgG4 levels to exclude autoimmune hepatitis and IgG4-related sclerosing cholangitis 1
• Wilson disease screening (especially in patients <40 years): serum ceruloplasmin, 24-hour urinary copper, and slit-lamp examination for Kayser-Fleischer rings 1
• In Wilson disease presenting as acute liver failure, look for the characteristic pattern: Coombs-negative hemolytic anemia, modest AST/ALT elevations (typically <2000 IU/L), and markedly subnormal alkaline phosphatase (typically <40 IU/L) with alkaline phosphatase to bilirubin ratio <2 1

Critical Imaging Studies

• Abdominal ultrasound is mandatory to exclude biliary obstruction, which must be ruled out before diagnosing alcoholic hepatitis 1, 4
• Ultrasound can identify hepatomegaly, ascites, and features of chronic liver disease 1
• For cholestatic patterns (elevated GGT or alkaline phosphatase), imaging helps distinguish primary sclerosing cholangitis from other biliary disorders 1

Detailed Alcohol History

Document the following specific details:

• Quantity: Average daily consumption in grams (>40 g/day for women, >50-60 g/day for men are minimal thresholds) 1
• Duration: Heavy drinking typically >5 years, with >6 months of heavy use and <60 days abstinence before jaundice onset required for alcoholic hepatitis diagnosis 1
• Pattern: Recent cessation (days to weeks before symptom onset is common in alcoholic hepatitis) 1
• Consider measuring ethyl glucuronide (EtG) in urine or hair for objective confirmation of alcohol consumption 1

Severity Assessment

Calculate prognostic scores to determine disease severity and need for specific therapy:

• Maddrey Discriminant Function (mDF): 4.6 × (patient's PT - control PT in seconds) + serum bilirubin (mg/dL) 1
  • mDF ≥32 defines severe alcoholic hepatitis with 50-65% survival without treatment 1
  • mDF <32 indicates 90% survival rate 1
• MELD score: Useful for prognosis, with scores ≥21 indicating poor prognosis 1
• Glasgow Alcoholic Hepatitis Score (GAHS): Helps identify patients who may benefit from corticosteroids (GAHS ≥9 indicates poor prognosis without treatment) 1

Role of Liver Biopsy

• Liver biopsy (via transjugular route) is useful but not mandatory for confirming alcoholic steatohepatitis and has prognostic value 1
• Biopsy should be performed when there is diagnostic uncertainty, as 10-20% of clinically diagnosed alcoholic hepatitis cases have other liver diseases 1
• Histologic hallmarks include macrovesicular steatosis with ≥1 of: neutrophil infiltration, hepatocyte ballooning, and Mallory-Denk bodies 1
• The presence of cirrhosis on biopsy significantly impacts prognosis (35% 4-year survival with cirrhosis vs 58% without) 1

Common Pitfalls to Avoid

• Do not assume alcoholic hepatitis without stringent criteria: Recent jaundice onset, AST >50 IU/mL with AST:ALT >1.5, bilirubin >3 mg/dL, and documented heavy alcohol use 1
• Do not miss drug-induced liver injury: AST/ALT typically exceed 400 IU/mL in DILI, unlike alcoholic hepatitis 1
• Do not overlook cirrhosis: An AST:ALT ratio >1.0 in nonalcoholic liver disease strongly suggests underlying cirrhosis 1, 2
• Do not forget to assess for complications: Check for ascites, hepatic encephalopathy, bacterial infections, acute kidney injury, and variceal bleeding 1

Monitoring for Complications

• Screen for bacterial infections (present in up to 25% of severe alcoholic hepatitis cases) 1
• Monitor renal function for hepatorenal syndrome (Type 1) 1
• Assess for hepatic encephalopathy and gastrointestinal bleeding 1
• Check platelet count, as thrombocytopenia suggests portal hypertension or cirrhosis 1