Which single therapy is most appropriate for a 51‑year‑old man with severe alcoholic hepatitis (MELD 33, AST 389 U/L, ALT 112 U/L, bilirubin 15 mg/dL, INR 1.8, creatinine 3.4 mg/dL, ascites, leukocytosis) – antibiotics, nutritional support with folic acid and thiamine, pentoxifylline, corticosteroids, or granulocyte‑colony stimulating factor?

Treatment of Severe Alcoholic Hepatitis with MELD 33

Corticosteroids (prednisolone 40 mg daily for 28 days) are the single most appropriate therapy for this patient with severe alcoholic hepatitis, as he meets criteria with MELD 33 (>20) and Maddrey discriminant function >32, and has no absolute contraindications. 1

Why Steroids Are the Answer

The American Association for the Study of Liver Diseases explicitly states that MELD score >20 should prompt consideration of steroid treatment, and this patient's MELD of 33 clearly exceeds this threshold. 1 The 2019 AASLD guidance confirms corticosteroids significantly reduce 28-day mortality in severe alcoholic hepatitis when MDF ≥32 or MELD >20. 1

Calculating Disease Severity

• Maddrey Discriminant Function: Using INR 1.8 and bilirubin 15.4, this patient's MDF is approximately 47, well above the threshold of 32 for severe disease requiring treatment. 1
• MELD 33 alone indicates extremely high short-term mortality without intervention. 1, 2

Why the Other Options Are Incorrect

Nutritional Support Alone

While nutritional therapy with thiamine and folic acid is essential supportive care that must accompany steroids, it is not sufficient as monotherapy for severe disease. 1 The AASLD guidelines show enteral nutrition reduces mortality by 36% (HR 0.64), but this benefit is additive to, not a replacement for, corticosteroids in severe alcoholic hepatitis. 1 Nutritional support should provide 30-40 kcal/kg/day and 1.2-1.5 g protein/kg/day alongside steroid therapy. 2, 3

Pentoxifylline

The 2019 AASLD guidance explicitly recommends avoiding pentoxifylline as it provides no survival benefit. 4 The large STOPAH trial with 270 patients demonstrated pentoxifylline combined with prednisolone showed no benefit over corticosteroids alone. 1 While earlier studies suggested pentoxifylline reduced hepatorenal syndrome, this has not been confirmed in high-quality recent trials. 1

Antibiotics Alone

Antibiotics are critical for infection screening and treatment before initiating steroids, but are not primary therapy for alcoholic hepatitis itself. 1 This patient should have blood cultures, urine cultures, and diagnostic paracentesis performed immediately, with antibiotics given only if infection is documented. 4, 2 Infections occur in 12-26% at admission and up to 50% during steroid treatment, making surveillance essential but not the primary intervention. 1

G-CSF

While one 2019 randomized trial showed G-CSF reduced 90-day mortality in steroid non-responders (Lille score >0.45), it is not first-line therapy. 5 G-CSF should only be considered after steroid failure is documented at day 7, not as initial treatment. 5

Critical Implementation Steps

Before Starting Steroids

• Screen for contraindications: Active GI bleeding, uncontrolled infection, acute pancreatitis, or renal failure. 1, 3
• Obtain cultures: Blood, urine, and ascitic fluid (given his ascites) before initiating therapy. 4, 2
• Address the elevated creatinine (3.4): This patient has acute kidney injury, likely hepatorenal syndrome. Avoid nephrotoxins (NSAIDs, aminoglycosides, IV contrast), use diuretics cautiously, and consider albumin with vasoconstrictors. 1, 3

Steroid Regimen

• Prednisolone 40 mg daily orally (or methylprednisolone 32 mg IV if unable to take oral) for 28 days, followed by either abrupt discontinuation or 2-week taper. 4, 2

Day 7 Response Assessment

• Calculate Lille score at day 7 using age, albumin, change in bilirubin from day 0 to day 7, creatinine, and INR. 4
• If Lille ≥0.56 (null responder): Stop steroids immediately—continuing exposes to infection risk without benefit. 4
• If Lille 0.45-0.56 (partial responder): Consider stopping on case-by-case basis. 4
• If Lille <0.45 (good responder): Continue full 28-day course (85% 6-month survival). 2

Mandatory Concurrent Supportive Care

• Complete alcohol abstinence: Essential for any survival benefit. 1, 3
• Aggressive nutrition: 30-40 kcal/kg/day, 1.2-1.5 g protein/kg/day via enteral route. 2, 3
• Vitamin supplementation: Thiamine, folic acid, vitamin B12, pyridoxine, vitamin D, and zinc. 4, 3
• Infection surveillance: Repeat cultures if clinical deterioration occurs, as 25% develop infections during first month of steroid treatment. 4

Common Pitfalls to Avoid

The most critical error is continuing steroids in non-responders (Lille ≥0.56), which exposes patients to infection without survival benefit and delays consideration of liver transplantation. 4 With MELD 33, this patient should be evaluated for early liver transplantation if he proves to be a steroid non-responder at day 7. 1, 4

Do not withhold steroids due to elevated creatinine alone—while this increases risk, it is not an absolute contraindication if infection is ruled out and hepatorenal syndrome is managed supportively. 1