What is the most likely diagnosis and immediate management for a 45‑year‑old chronic alcoholic presenting with severe anemia, oral ulcerations, anorexia, mild hyperbilirubinemia, normal renal function and electrolytes, and mild splenomegaly?

Diagnosis: Severe Alcoholic Hepatitis with Macrocytic Anemia and Possible Hemolysis

This patient most likely has severe alcoholic hepatitis with macrocytic anemia, and immediate management requires calculating the Maddrey Discriminant Function (MDF) score to determine if corticosteroid therapy is indicated, while simultaneously initiating thiamine 500 mg IV three times daily, enforcing absolute alcohol abstinence, and providing aggressive nutritional support. 1, 2

Immediate Diagnostic Assessment

Calculate severity scores immediately to stratify mortality risk:

• MDF score ≥32 indicates severe disease with 40-50% mortality at 90 days without treatment 2
• MELD score >20 predicts high 90-day mortality and triggers consideration for corticosteroid therapy 1, 2
• The combination of macrocytic anemia (Hb 5.5), mild hyperbilirubinemia (predominantly indirect at 1.2 mg/dL), splenomegaly, anorexia, and oral ulcers in a chronic alcoholic strongly suggests alcoholic hepatitis with underlying cirrhosis and possible hemolysis 1

Screen for infections before any treatment:

• Obtain blood cultures, urine cultures, and diagnostic paracentesis (if ascites present) immediately, even without fever, as infection is present in 20-30% of severe alcoholic hepatitis cases 2
• Do not start corticosteroids until active infection, hepatitis B, tuberculosis, and GI bleeding are excluded 2

Universal Immediate Interventions (All Patients)

Thiamine administration is critical and time-sensitive:

• Administer thiamine 500 mg IV three times daily for 3-5 days BEFORE any glucose-containing solutions to prevent Wernicke's encephalopathy 1, 2
• This is non-negotiable in all chronic alcoholics with malnutrition 1

Enforce complete alcohol abstinence:

• This is the single most important intervention and cornerstone of all treatment, improving both short-term and long-term survival 1, 3, 2

Provide aggressive nutritional support:

• 35-40 kcal/kg ideal body weight daily and 1.2-1.5 g/kg/day protein, as protein-calorie malnutrition is present in almost every patient with severe alcoholic hepatitis 1, 2

Addressing the Severe Anemia (Hb 5.5)

The macrocytic anemia has multiple potential etiologies in this alcoholic patient:

Megaloblastic anemia from folate/B12 deficiency:

• Chronic alcoholics commonly develop megaloblastic anemia due to poor nutrition and direct toxic effects 4
• Consider checking folate and B12 levels, though treatment should not be delayed pending results 5

Acquired sideroblastic anemia:

• 17% of chronic alcoholics with anemia show ring sideroblasts on bone marrow examination, even with macrocytic picture on peripheral smear 4
• This represents direct bone marrow toxicity from alcohol 4, 6
• Sideroblastic anemia should be ruled out in chronic alcoholics with anemia not responding to vitamin B12/folate 4

Hemolytic component (Zieve's syndrome or alcohol-induced hemolysis):

• The predominantly indirect hyperbilirubinemia (1.2 mg/dL indirect vs 0.8 mg/dL direct) suggests hemolysis in addition to hepatic dysfunction 7
• Zieve's syndrome presents with the triad of jaundice, hemolytic anemia, and hyperlipidemia in chronic alcohol use, though hyperlipidemia may be absent 7
• Alcohol can directly alter erythrocyte membrane phospholipid composition, causing echinocytosis and hemolysis 8
• Check reticulocyte count, LDH, haptoglobin, and direct Coombs test to confirm non-immune hemolysis 7

Transfusion considerations:

• With Hb 5.5, transfusion may be necessary for symptomatic anemia, but recognize that transfused cells may acquire the same membrane defects if alcohol-induced hemolysis is present 8
• Transfusion should be guided by symptoms rather than arbitrary thresholds in this setting

Corticosteroid Therapy Decision

If MDF ≥32 or MELD >20 AND no contraindications exist:

• Start prednisolone 40 mg daily for 28 days 1, 2
• Corticosteroids provide modest survival benefit at 28 days but no benefit beyond 28 days 2

Calculate Lille score on day 7:

• If Lille score ≥0.45, stop corticosteroids immediately as non-responders have increased risk of infection and death 1, 2

Critical Monitoring

Avoid nephrotoxic agents:

• Do not use diuretics or other nephrotoxic drugs, as acute kidney injury is an early manifestation of multi-organ failure syndrome with very high mortality 1

Monitor for complications:

• Infections (20-30% incidence, primary trigger for multi-organ failure) 2
• Hepatorenal syndrome, hepatic encephalopathy, variceal bleeding 2
• Multi-organ failure, especially if SIRS is present on admission 1

Liver Transplantation Consideration

If MELD >26:

• Refer for early liver transplantation evaluation, as 90-day mortality is very high and traditional 6-month abstinence requirement may be waived in select cases of severe alcoholic hepatitis 1

Common Pitfalls to Avoid

• Do not give glucose before thiamine – this can precipitate Wernicke's encephalopathy 1, 2
• Do not assume anemia is purely megaloblastic – check for hemolysis and consider sideroblastic anemia if not responding to B12/folate 4
• Do not start corticosteroids without excluding infection – this increases mortality in infected patients 2
• Do not continue corticosteroids beyond day 7 if Lille score ≥0.45 – this only increases infection risk without benefit 1, 2