Is prednisone a reasonable treatment for most types of hepatitis?

Prednisone is NOT a reasonable treatment for most types of hepatitis

Prednisone is contraindicated or harmful in most forms of hepatitis, with the critical exception of autoimmune hepatitis where it is the cornerstone of therapy. The type of hepatitis determines whether corticosteroids will be life-saving or potentially fatal.

When Prednisone is Absolutely Contraindicated

Viral Hepatitis (Hepatitis B and C)

• Prednisone priming (steroid pretreatment) is not recommended as primary treatment for chronic hepatitis B due to risk of fatal exacerbations, particularly in patients with underlying cirrhosis 1
• A meta-analysis of 7 randomized trials showed no significant benefit of steroid pretreatment in 376 patients with HBeAg-positive chronic hepatitis B 1
• While one European study suggested benefit, the risk of fatal hepatic decompensation in cirrhotic patients outweighs any potential advantage 1
• Hepatitis B virus reactivation can occur in hepatitis B carriers treated with immunosuppressive doses of corticosteroids, and reactivation can be severe or fatal 2

Other Contraindicated Situations

• Corticosteroids should be avoided in cerebral malaria 2
• Prednisone may activate latent amebiasis and should not be used until this is ruled out in at-risk patients 2
• In patients with Strongyloides infestation, corticosteroids can lead to hyperinfection syndrome with potentially fatal gram-negative septicemia 2

When Prednisone is Essential: Autoimmune Hepatitis

First-Line Treatment Indications

Prednisone (with or without azathioprine) is the established standard of care for autoimmune hepatitis and should be initiated in all patients with active disease 1, 3

Treatment is absolutely indicated when 1, 3:

• Serum AST >10-fold upper limit of normal
• Serum AST >5-fold upper limit of normal AND γ-globulin ≥2× upper limit of normal
• Histologic features show bridging necrosis or multiacinar necrosis

Treatment Regimens for Autoimmune Hepatitis

The combination regimen of prednisone plus azathioprine is preferred over prednisone alone because it achieves similar efficacy with significantly fewer corticosteroid-related side effects (10% vs 44%) 1

Standard adult regimen 1:

• Week 1: Prednisone 30 mg/day + Azathioprine 50 mg/day
• Week 2: Prednisone 20 mg/day + Azathioprine 50 mg/day
• Week 3-4: Prednisone 15 mg/day + Azathioprine 50 mg/day
• Maintenance: Prednisone 10 mg/day + Azathioprine 50 mg/day until endpoint

Alternative monotherapy regimen (for pregnant women, those with cytopenia, thiopurine methyltransferase deficiency, or short treatment trials) 1:

• Week 1: Prednisone 60 mg/day
• Week 2: Prednisone 40 mg/day
• Week 3-4: Prednisone 30 mg/day
• Maintenance: Prednisone 20 mg/day

Treatment Outcomes in Autoimmune Hepatitis

• Remission can be achieved in 80% of patients within 3 years, with 10- and 20-year survival rates exceeding 80% 4
• Biochemical remission should be achieved within 6 months and is associated with lower frequency of progression to cirrhosis 3
• Complete normalization of transaminases and IgG levels should be the treatment goal 3

Critical Safety Considerations

Long-term corticosteroid complications 1, 3:

• 80% develop cosmetic changes (facial rounding, acne, truncal obesity) after 2 years
• Severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop after 18 months at doses >10 mg/day
• Only 13% require premature drug withdrawal due to side effects 5

Monitoring requirements 1:

• Baseline and annual bone mineral densitometry for patients on long-term therapy
• Periodic eye examinations for cataracts and glaucoma
• Leukopenia and thrombocytopenia monitoring with azathioprine

Special Populations

Acute Severe Autoimmune Hepatitis

High-dose intravenous corticosteroids (≥1 mg/kg) should be administered as early as possible 3

• If no improvement within 7 days, evaluate for liver transplantation 3

Cirrhotic Patients

• Prednisone is safe and effective in compensated cirrhosis 1
• Avoid in Child's class B or C cirrhosis due to risk of hepatic decompensation, bacterial infection, and disease exacerbation 1

Children

Treatment is warranted in most children at diagnosis with initial prednisone 2 mg/kg daily (up to 60 mg/day) with or without azathioprine 1

Common Pitfalls to Avoid

1. Never use prednisone empirically for "hepatitis" without knowing the etiology - viral hepatitis can be fatally exacerbated 1, 2
2. Screen for hepatitis B before initiating immunosuppressive treatment to prevent reactivation 2
3. Do not undertreated autoimmune hepatitis - incomplete response leads to progression and worse outcomes 3
4. Recognize that advanced cirrhosis impairs prednisone-to-prednisolone conversion, but this is usually insufficient to warrant switching to prednisolone 1, 6