Can steroids be given to patients presenting with fulminant hepatitis?

Management of Fulminant Hepatitis: Steroid Use

Corticosteroids should not be given to patients with fulminant hepatitis with severe coagulopathy and hepatic encephalopathy grade III-IV, as they show no benefit and may delay life-saving liver transplantation. 1

Types of Fulminant Hepatitis and Steroid Indications

Autoimmune Fulminant Hepatitis

• Patients with acute severe autoimmune hepatitis (AS-AIH) with severe coagulopathy and hepatic encephalopathy grade III-IV should not receive corticosteroids but should be considered for early liver transplantation 1
• In less severe presentations of AS-AIH (without high-grade encephalopathy), early introduction of high-dose corticosteroids (1 mg/kg/day) may be beneficial and should be considered as early as possible 1
• Low-grade hepatic encephalopathy is not a contraindication to corticosteroid therapy in AS-AIH 1

Alcoholic Fulminant Hepatitis

• For severe alcoholic hepatitis (defined by Maddrey Discriminant Function score ≥32), prednisolone 40 mg daily for 28 days is the standard treatment 1, 2
• Response should be assessed after 7 days using the Lille model; patients with scores ≥0.56 (null responders) should have steroids discontinued 1, 2
• Pentoxifylline (400 mg three times daily for 28 days) may be considered as an alternative in patients with contraindications to steroids 1, 3

Immune Checkpoint Inhibitor-Induced Fulminant Hepatitis

• For grade 4 immune checkpoint inhibitor hepatitis (AST/ALT >20× ULN or bilirubin >10× ULN or hepatic decompensation with ascites or encephalopathy), patients should be hospitalized at a center with expertise in liver failure 1
• Treatment includes 2 mg/kg/day methylprednisolone with a planned 4-6 week taper 1
• If no response to steroids within 3 days (defined as <50% drop in transaminases), second-line immunosuppression with mycophenolate mofetil, azathioprine, or tacrolimus should be initiated 1

Predictors of Poor Response to Steroids

• High MELD score (>40) is associated with decreased survival with steroid use in fulminant hepatitis 4
• Encephalopathy grade 3 or higher significantly predicts corticosteroid failure in fulminant autoimmune hepatitis 5
• A Spanish study found that a nomogram combining older age, MELD score, encephalopathy, and ascites at initiation of corticosteroids accurately predicts response to therapy 1

Decision Algorithm for Steroid Use in Fulminant Hepatitis

1. Determine etiology of fulminant hepatitis (autoimmune, alcoholic, drug-induced, viral, etc.) 1

2. Assess severity using:

   • Encephalopathy grade (I-IV) 1
   • Coagulopathy (INR) 1
   • MELD score 5, 4

3. For autoimmune fulminant hepatitis:

   • If severe coagulopathy AND encephalopathy grade III-IV: Do not give steroids, proceed to liver transplantation evaluation 1
   • If low-grade or no encephalopathy: Consider corticosteroids (prednisolone 1 mg/kg/day) 1
   • Monitor response: If no improvement or worsening in liver biochemistry or development/worsening of hepatic encephalopathy, consider early liver transplantation 1

4. For alcoholic fulminant hepatitis:

   • If Maddrey score ≥32: Start prednisolone 40 mg daily 1, 2
   • Assess response at day 7 using Lille model 1, 2
   • If Lille score ≥0.56: Discontinue steroids 1

Important Caveats

• Corticosteroid therapy in fulminant hepatitis may delay liver transplantation evaluation and precipitate postoperative complications such as infection, bleeding, or poor wound healing 6
• A multivariate analysis showed that mechanical ventilation, MELD score, and ALT levels were significant predictors of spontaneous survival, not steroid use 4
• In patients with the highest MELD scores (>40), steroid use was associated with significantly lower survival (30% versus 57%) 4
• Liver biopsy should be considered before starting glucocorticoids to maximize diagnostic utility and confirm etiology 1

Summary

The decision to use steroids in fulminant hepatitis must be based on the underlying etiology and severity of presentation. For patients with severe autoimmune hepatitis with high-grade encephalopathy and coagulopathy, steroids provide no benefit and may delay life-saving liver transplantation. Early liver transplantation evaluation is critical for patients with poor prognostic indicators such as high MELD scores and high-grade encephalopathy.