Why do steroids help in alcoholic hepatitis but not in other forms of hepatitis, such as viral hepatitis?

Why Steroids Work in Alcoholic Hepatitis But Not Other Forms of Hepatitis

Steroids are effective in severe alcoholic hepatitis because they specifically target the unique inflammatory cascade driven by TNF-α and other pro-inflammatory cytokines that characterize this disease, whereas other forms of hepatitis (particularly viral hepatitis) have fundamentally different pathophysiologic mechanisms that do not respond to—and may be worsened by—immunosuppression. 1

The Unique Inflammatory Mechanism in Alcoholic Hepatitis

Alcoholic hepatitis is fundamentally an inflammatory disease, not an infectious one. The pathophysiology centers on:

• Excessive TNF-α production that drives hepatocyte injury and necrosis 1
• Elevated intercellular adhesion molecule-1 (ICAM-1) levels that correlate with disease severity 1
• Pro-inflammatory cytokine storm including IL-8 and macrophage inflammatory protein-1a 2

Prednisolone 40 mg daily works by directly reducing transcription of these pro-inflammatory cytokines, with measurable decreases in TNF-α and ICAM-1 levels that correlate with histological improvement 1. This mechanism is highly specific to the alcohol-induced inflammatory cascade.

Why This Doesn't Apply to Viral Hepatitis

The critical difference lies in disease mechanism:

• Viral hepatitis requires active immune response to clear infected hepatocytes—suppressing this response with steroids would allow viral replication to accelerate
• Alcoholic hepatitis has no pathogen to clear—the injury is purely inflammatory from toxic metabolites and cytokine release
• Immunosuppression in viral hepatitis is counterproductive, potentially leading to viral reactivation and fulminant hepatic failure

Evidence of Efficacy in Severe Alcoholic Hepatitis

The therapeutic window is remarkably specific:

• Steroids improve 28-day survival from 65.1% (placebo) to 84.6% (steroid group) in patients with mDF ≥32 1
• Maximum benefit occurs with MELD scores 25-39, showing 21-30% survival benefit 3
• No benefit above MELD 51, where patients are too sick to respond 3
• Primary benefit is reducing liver failure-related death (OR 0.46), not infection-related mortality 4

The Response Assessment Algorithm

Treatment response must be assessed at day 7 using validated scoring systems 1, 5:

• Lille score ≤0.16 (complete responders): 91.1% 28-day survival—continue full 28-day course 1, 5
• Lille score 0.16-0.56 (partial responders): 79.4% 28-day survival—continue treatment 1, 5
• Lille score ≥0.56 (null responders): 53.3% 28-day survival—discontinue steroids immediately due to increased infection risk without benefit 1, 5, 2

Critical Caveats and Pitfalls

The median time from admission to steroid initiation should be 6.5 days 6, allowing thorough evaluation to exclude contraindications:

• Active infection or sepsis (steroids increase fungal infection risk specifically) 5, 4
• Gastrointestinal bleeding 1, 5
• Acute renal failure 1, 5
• Acute pancreatitis 1, 5

Common mistake: Starting steroids too quickly without adequate infection screening. While steroids don't increase bacterial infection rates overall 4, fungal infections occur more frequently (8 of 528 steroid-treated vs. 1 of 534 controls) 4, and all fungal infection deaths occurred in the steroid arm 4.

Vigilant monitoring is essential in the first month when most infections occur 6. After completing 28 days, taper over 2 weeks rather than abrupt cessation 5, 6.

Why Alternative Treatments Fail

• Pentoxifylline is inferior to prednisolone (74.5% vs. 87.0% 1-month survival) 2 and should only be used when steroids are contraindicated 5, 2
• Pentoxifylline does NOT work as rescue therapy for steroid non-responders 2
• For null responders, liver transplantation is the primary rescue option, showing significantly higher survival than continued medical therapy 1, 2

The Bottom Line on Mechanism Specificity

Steroids work in alcoholic hepatitis because the disease is purely inflammatory cytokine-mediated injury without an infectious agent requiring immune clearance. This stands in stark contrast to viral hepatitis, where the immune system must remain active to eliminate infected cells. The 28-day survival benefit (but not 90-day benefit) 3, 7 underscores that steroids buy time for liver recovery in a specific therapeutic window, but long-term outcomes depend entirely on achieving alcohol abstinence 5, 2.