What is the likely diagnosis and initial management for a 48‑year‑old chronic alcoholic presenting with markedly elevated alkaline phosphatase, moderately increased aspartate aminotransferase, relatively low alanine aminotransferase, and total bilirubin of 7 mg/dL?

Likely Diagnosis: Alcoholic Hepatitis with Cholestatic Features

This 48-year-old chronic alcoholic presenting with markedly elevated alkaline phosphatase (ALP 461 U/L), disproportionately elevated AST (165 U/L) compared to ALT (36 U/L), and significant hyperbilirubinemia (total bilirubin 7 mg/dL) most likely has alcoholic hepatitis with prominent cholestatic features.

Key Diagnostic Features

AST/ALT Ratio Analysis

• The AST/ALT ratio is 4.6 (165/36), which is highly specific for alcoholic liver disease. An AST/ALT ratio >2 is characteristic of alcoholic liver disease, with ratios >3 being particularly specific for this diagnosis 1, 2.
• In alcoholic hepatitis, 70% of patients demonstrate an AST/ALT ratio >2, and the ratio of >1.5 is seen in >98% of histologically proven cases 3.
• The absolute AST and ALT values (typically not exceeding 400 IU/mL in alcoholic hepatitis) fit this pattern 3.

Cholestatic Pattern

• The markedly elevated ALP (461 U/L, approximately 4× upper limit of normal) indicates significant intrahepatic cholestasis, which occurs in alcoholic liver disease and is often secondary to alcoholic hepatitis 4.
• Patients with alcoholic liver disease can present with marked ALP elevation (>4× upper limit of normal) due to intrahepatic cholestasis, particularly when there is significant hepatocellular necrosis, alcoholic hyaline, and cholestasis on histology 4.
• The total bilirubin of 7 mg/dL confirms cholestasis and indicates moderate-to-severe hepatocellular dysfunction 3.

Pattern Recognition

• This combination—high AST/ALT ratio, markedly elevated ALP, and hyperbilirubinemia—represents a mixed hepatocellular-cholestatic injury pattern that is characteristic of alcoholic hepatitis 5.
• The relatively low ALT (36 U/L) compared to AST reflects the mitochondrial injury pattern typical of chronic alcohol toxicity 6.

Immediate Management Algorithm

Step 1: Confirm Diagnosis and Assess Severity (Day 0–2)

Complete the liver panel immediately:

• Obtain albumin, prothrombin time/INR, and complete blood count with platelets to assess synthetic function and rule out hepatic decompensation 3.
• Check gamma-glutamyl transferase (GGT) to confirm hepatic origin of ALP elevation; an elevated GGT confirms the ALP is liver-derived 5.
• Calculate the discriminant function (DF) score: DF = 4.6 × (prothrombin time – control) + total bilirubin (mg/dL). A DF ≥32 indicates severe alcoholic hepatitis with high short-term mortality 3.

Rule out biliary obstruction:

• Perform abdominal ultrasound with Doppler to exclude extrahepatic biliary obstruction, assess for ascites, evaluate liver echotexture, and check portal vein patency 3.
• Even though the clinical picture strongly suggests alcoholic hepatitis, biliary obstruction must be excluded when ALP is >4× upper limit of normal 4, 5.

Exclude competing diagnoses:

• Obtain viral hepatitis serologies (HBsAg, anti-HBc IgM, anti-HCV) to rule out viral hepatitis, which can cause fluctuating transaminase elevations 3.
• Check autoimmune markers (ANA, anti-smooth muscle antibody, quantitative IgG) if there is any atypical feature suggesting autoimmune hepatitis 7, 3.

Step 2: Initiate Supportive Care and Alcohol Cessation (Day 0–7)

Mandate complete alcohol abstinence:

• Immediate and complete alcohol cessation is the single most important intervention; even moderate alcohol consumption will prevent recovery and worsen outcomes 3.
• Assess for alcohol withdrawal syndrome and provide benzodiazepine prophylaxis if indicated (CIWA protocol) 3.

Nutritional support:

• Provide high-calorie, high-protein nutrition (1.2–1.5 g protein/kg/day) unless hepatic encephalopathy is present 3.
• Supplement thiamine (100 mg IV/PO daily), folate, and multivitamins to address common deficiencies in chronic alcoholics 3.

Monitor for complications:

• Assess daily for hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and variceal bleeding 3.
• If ascites develops, initiate sodium restriction (<2 g/day) and diuretics (spironolactone ± furosemide) 3.

Step 3: Consider Corticosteroid Therapy (Day 2–5)

If discriminant function ≥32 or hepatic encephalopathy is present:

• Initiate prednisolone 40 mg daily for 28 days, as corticosteroids reduce short-term mortality in severe alcoholic hepatitis 3.
• Exclude active infection (blood cultures, urinalysis, diagnostic paracentesis if ascites present) and gastrointestinal bleeding before starting corticosteroids 3.
• Contraindications to corticosteroids include active infection, gastrointestinal bleeding, renal failure, and pancreatitis 3.

Assess response at Day 7:

• Calculate the Lille score at Day 7 to predict corticosteroid response; a Lille score ≥0.45 indicates non-response and poor prognosis 3.
• If non-responsive, discontinue corticosteroids and consider early liver transplant evaluation 3.

Step 4: Ongoing Monitoring and Hepatology Referral (Week 1–4)

Repeat liver enzymes every 2–5 days initially:

• Monitor AST, ALT, ALP, bilirubin, albumin, and INR to track response to treatment 3.
• Expect gradual improvement in bilirubin and synthetic function over 2–4 weeks with abstinence 3.

Hepatology referral is mandatory:

• Refer immediately to hepatology given the severity of presentation (bilirubin 7 mg/dL, AST >5× upper limit of normal) 3.
• Hepatology consultation is essential for prognostication, consideration of liver biopsy if diagnosis is uncertain, and evaluation for liver transplantation if severe disease persists 3.

Calculate FIB-4 score once acute hepatitis resolves:

• Use age, AST, ALT, and platelet count to assess for underlying cirrhosis; a FIB-4 >2.67 indicates high risk for advanced fibrosis 3.
• If FIB-4 suggests cirrhosis, initiate surveillance for hepatocellular carcinoma (ultrasound every 6 months) and esophageal varices (upper endoscopy) 3.

Critical Pitfalls to Avoid

• Do not assume biliary obstruction is absent without imaging—even though the AST/ALT ratio strongly suggests alcoholic liver disease, marked ALP elevation (>4× upper limit of normal) mandates ultrasound to exclude extrahepatic obstruction 4, 5.

• Do not delay hepatology referral—bilirubin of 7 mg/dL with AST >5× upper limit of normal meets criteria for urgent specialist evaluation 3.

• Do not overlook hepatic decompensation—check for ascites, encephalopathy, coagulopathy, and variceal bleeding, as these complications require immediate intervention 3.

• Do not start corticosteroids without excluding infection and bleeding—active infection or gastrointestinal hemorrhage are absolute contraindications to corticosteroid therapy 3.

• Do not underestimate the importance of complete alcohol abstinence—even moderate drinking will prevent recovery and worsen prognosis; involve addiction services early 3.

• Do not forget nutritional support—chronic alcoholics are universally malnourished and require thiamine, folate, and high-calorie/high-protein nutrition 3.