What is the diagnosis for an elderly female with pruritus, alcohol dependence, negative hepatitis B (HBV) and negative hepatitis C (HCV) screen, hyperphosphatemia, and hyperbilirubinemia?

Diagnosis: Alcoholic Hepatitis with Cholestatic Features

The most likely diagnosis is alcoholic hepatitis presenting with a cholestatic pattern, characterized by elevated bilirubin and pruritus in the setting of chronic alcohol dependence. 1

Clinical Presentation and Diagnostic Criteria

This patient meets the diagnostic criteria for alcoholic hepatitis based on:

• History of alcohol dependence with presumed heavy consumption (>20 g/day for women) for likely >6 months 1
• Hyperbilirubinemia (elevated bilirubin >3 mg/dL is typical) 1
• Diffuse pruritus, which occurs in cholestatic liver disease due to accumulation of pruritogens, particularly lysophosphatidic acid and bile salts 2, 3
• Negative viral hepatitis screening (HBV and HCV excluded) 1

The elevated phosphate levels mentioned are likely alkaline phosphatase (ALP), which indicates a cholestatic pattern of alcoholic hepatitis—an uncommon but well-documented presentation. 4, 5

Key Diagnostic Features of Alcoholic Hepatitis

Laboratory Pattern Expected:

• AST/ALT ratio typically >1.5-2.0, with AST >50 IU/mL but rarely >400 IU/mL 1
• Conjugated (direct) hyperbilirubinemia predominates in cholestatic alcoholic hepatitis 1, 4, 5
• Elevated alkaline phosphatase can occur without biliary obstruction 4, 5
• Additional findings may include anemia, leukocytosis, thrombocytopenia, prolonged prothrombin time, and hypoalbuminemia 1

Critical Diagnostic Algorithm:

1. Fractionate the bilirubin to confirm conjugated hyperbilirubinemia (direct bilirubin >35% of total) 1, 6

2. Obtain abdominal ultrasound within 24-48 hours to exclude biliary obstruction—this is mandatory with 98% positive predictive value for liver parenchymal disease 1, 6

3. Check complete liver panel: AST, ALT, GGT, albumin, PT/INR to assess severity and synthetic function 1, 6

4. Consider transjugular liver biopsy if diagnostic uncertainty exists or to guide treatment decisions, particularly if considering corticosteroids 1

Histologic Confirmation

If liver biopsy is performed, expect:

• Steatohepatitis with macrovesicular steatosis and hepatocyte ballooning 1
• Intrahepatic cholestasis (bilirubinostasis) explaining the pruritus and elevated bilirubin 1
• Neutrophilic infiltration with Mallory-Denk bodies 1
• "Chicken-wire" fibrosis pattern, with most severe cases showing underlying cirrhosis 1
• Severe intra-parenchymal cholestasis is an independent predictor of short-term mortality 1

Differential Diagnoses to Exclude

Must rule out:

• Biliary obstruction (choledocholithiasis, cholangitis, pancreatic mass)—ultrasound is first-line imaging 1, 6
• Drug-induced liver injury (DILI)—AST/ALT typically >400 IU/mL in DILI, unlike alcoholic hepatitis 1
• Autoimmune hepatitis—check ANA, ASMA, immunoglobulins 1
• Primary biliary cholangitis or primary sclerosing cholangitis—if ultrasound negative but suspicion high, proceed to MRCP 1, 6

Management of Pruritus

For the diffuse itching, initiate cholestyramine as first-line therapy:

• Cholestyramine 4-16 g/day in divided doses binds bile acids in the intestine, reducing enterohepatic circulation and dermal deposition 7, 2
• Administer before meals for optimal bile acid binding 7

Second-line options if cholestyramine fails:

• Rifampicin 150-300 mg twice daily to alter pruritogen metabolism 2, 3
• Naltrexone or naloxone (μ-opioid antagonists) for central perception modulation 2, 3
• SSRIs for refractory cases 2, 3

Prognostic Assessment

Calculate severity scores to guide treatment:

• Maddrey Discriminant Function (MDF) = 4.6 × (patient's PT - control PT) + total bilirubin (mg/dL) 1
• MDF ≥32 indicates severe disease with 30-50% one-month mortality without treatment 1
• MELD score ≥18 also predicts poor prognosis 1

Critical Pitfalls to Avoid

1. Do not assume all pruritus with liver disease is from bile salts alone—lysophosphatidic acid is now recognized as a key pruritogen 2, 3

2. Do not miss biliary obstruction—always obtain ultrasound before attributing symptoms solely to alcoholic hepatitis, as 10-20% of clinically diagnosed cases have alternative diagnoses 1

3. Do not overlook cholestatic alcoholic hepatitis—while uncommon, it presents with direct hyperbilirubinemia and elevated ALP without obstruction 4, 5

4. Check vitamin K status before attributing prolonged INR to liver dysfunction—fat-soluble vitamin deficiencies are common in cholestasis and correctable 6

5. AST/ALT ratio <1.5 occurs in <2% of biopsy-proven alcoholic hepatitis—if ratio is atypical, strongly consider alternative diagnoses 1