What is the role of silymarin in the treatment of acute severe hepatitis or acute liver failure in children?

Role of Silymarin and L-Ornithine L-Aspartate in Acute Severe Hepatitis or Acute Liver Failure in Children

There is insufficient evidence to recommend silymarin (Silybon) or L-ornithine L-aspartate (LOLA) as primary treatments for acute severe hepatitis or acute liver failure in children, and they should not be used in place of established treatments. 1

Current Management Approach for Acute Severe Hepatitis/ALF in Children

First-Line Management

• Glucocorticoid therapy (prednisone or prednisolone alone, 0.5-1 mg/kg daily in adults and up to 2 mg/kg in children) is the recommended first-line treatment for acute severe autoimmune hepatitis 1
• For acute liver failure (ALF), immediate evaluation for liver transplantation is recommended rather than prolonged medical therapy 1
• Treatment response should be assessed within 1-2 weeks; failure to improve laboratory tests or clinical deterioration warrants immediate consideration for liver transplantation 1

Monitoring and Response Assessment

• Rapid improvement in serum aminotransferase levels within 2 weeks is the most important indicator of favorable outcome 1
• Failure to improve any laboratory test reflecting liver inflammation or function, especially hyperbilirubinemia, requires immediate consideration of liver transplantation 1
• Hepatic encephalopathy at presentation defines ALF and indicates that liver transplantation is more likely to improve survival than protracted medical treatment 1

Evidence Regarding Silymarin (Silybon)

• There is no mention of silymarin in any of the major clinical practice guidelines for management of acute severe hepatitis or ALF in children 1
• A controlled trial of silymarin in acute viral hepatitis found no statistically significant differences in the decrease of bilirubin, transaminases, alkaline phosphatase, or prothrombin time compared to controls 2
• While silymarin has shown some benefit in chronic liver diseases due to its anti-inflammatory, antioxidant, and antifibrotic properties, evidence for its use in acute severe hepatitis or ALF in children is lacking 3, 4
• High-dose silymarin (1,050 mg/day) has shown some improvement in liver biochemical profiles in adults with decompensated HCV cirrhosis, but this cannot be extrapolated to acute liver failure in children 5

Evidence Regarding L-Ornithine L-Aspartate (LOLA)

• None of the major clinical practice guidelines for pediatric liver disease mention LOLA as a recommended treatment for acute severe hepatitis or ALF in children 1
• No specific studies evaluating LOLA in pediatric acute liver failure were provided in the evidence

Clinical Decision-Making Algorithm

1. For acute severe hepatitis in children:

   • Begin glucocorticoid therapy (prednisone/prednisolone up to 2 mg/kg daily) 1
   • Monitor laboratory tests and clinical status closely
   • If no improvement within 1-2 weeks, proceed to liver transplantation evaluation 1

2. For acute liver failure in children:

   • Proceed directly to liver transplantation evaluation 1
   • Provide supportive care while awaiting transplantation 6

3. Supportive management (for both conditions):

   • Manage coagulation disorders and hepatic encephalopathy 6
   • Consider artificial liver support as a bridge to transplantation 6
   • Monitor for complications including infection 1

Important Caveats

• Silymarin and LOLA should not delay definitive treatment or transplantation evaluation in acute severe hepatitis or ALF 1
• The etiology of acute hepatitis should be determined whenever possible, as management may differ based on cause (viral, autoimmune, toxic) 6
• Close monitoring is essential as the condition can deteriorate rapidly, requiring prompt intervention 7
• Parents should be educated about warning signs requiring immediate medical attention, including jaundice, abdominal distension or pain, changes in mental status, unusual bleeding or bruising, persistent vomiting, and fever 7