What is the treatment for poison-induced hepatitis?

Treatment of Poison-Induced Hepatitis

The cornerstone of treatment for poison-induced hepatitis is immediate discontinuation of the offending agent, with N-acetylcysteine being the specific antidote for acetaminophen toxicity and supportive care for most other drug-induced liver injuries. 1, 2

Immediate Management Steps

Identify and Stop the Offending Agent

• Discontinue all potentially hepatotoxic medications immediately upon suspicion of drug-induced hepatitis, retaining only essential medications 3, 1, 4
• Obtain detailed history of all prescription drugs, non-prescription medications, herbal supplements, and dietary products taken over the past year, including timing, dosage, and last dose 3, 4
• Verify ingredients of all non-prescription medications whenever possible 3

Specific Antidote Therapy

For Acetaminophen Poisoning

• Administer N-acetylcysteine intravenously as the specific antidote for acetaminophen-induced hepatotoxicity 2, 5
• Use the Rumack-Matthew nomogram to guide treatment decisions: if acetaminophen concentration is at or above the "possible toxicity line," immediately administer loading dose 2
• Total dosage: 300 mg/kg given as 3 sequential doses over 21 hours (loading dose followed by maintenance doses) 2
• For patients with risk factors (chronic alcohol use, malnutrition, concurrent hepatotoxic drugs like isoniazid), treat even if concentrations are in the non-toxic range 2

For Mushroom Poisoning (Amanita Species)

• Administer penicillin G (300,000 to 1 million units/kg/day IV) and silymarin (30-40 mg/kg/day) despite lack of controlled trial evidence 3
• Silymarin (milk thistle) has generally shown better success than penicillin G, though penicillin G is more readily available in the United States 3
• Consider gastric lavage and activated charcoal via nasogastric tube if patient presents within hours to one day of ingestion 3
• List patient for liver transplantation immediately, as this is often the only lifesaving option 3

Grading Severity and Treatment Escalation

Grade 1 Hepatitis (ALT/AST 1-3× ULN or bilirubin 1-1.5× ULN)

• Monitor liver chemistries once or twice weekly 3
• May continue treatment with close observation or delay dosing depending on clinical context 3

Grade 2 Hepatitis (ALT/AST >3-5× ULN or bilirubin >1.5-3× ULN)

• Hold all potentially hepatotoxic treatments 3, 1
• Consult gastroenterology or hepatology specialist 3
• For symptomatic patients: administer prednisone 0.5-1.0 mg/kg/day or equivalent 3
• If hepatitis fails to resolve after 1-2 week delay, initiate systemic glucocorticoids 3
• Consider liver biopsy before starting glucocorticoids to maximize diagnostic utility 3

Grade 3 Hepatitis (ALT/AST >5-20× ULN or bilirubin >3-10× ULN)

• Permanently discontinue the offending agent 3
• Urgent gastroenterology/hepatology consultation required 3
• Consider hospitalization and liver biopsy on case-by-case basis 3
• Initiate methylprednisolone 1-2 mg/kg/day or equivalent with planned 4-6 week taper 3
• If no response within 3-5 days, add second-line immunomodulators: azathioprine, mycophenolate mofetil, or tacrolimus 3
• Avoid infliximab due to potential idiosyncratic liver toxicity and lack of clinical benefit 3

Grade 4 Hepatitis (ALT/AST >20× ULN or bilirubin >10× ULN or hepatic decompensation)

• Hospitalize immediately, preferably at referral center with liver failure expertise 3
• Permanently discontinue all hepatotoxic agents 3
• Start methylprednisolone 2 mg/kg/day or equivalent with planned 4-6 week taper 3
• If transaminases fail to drop by at least 50% within 3 days, initiate secondary immunosuppression (azathioprine, mycophenolate mofetil, or tacrolimus) 3
• Antithymocyte globulin reserved only for refractory, severe cases 3
• List for liver transplantation as this may be the only lifesaving option 3, 5

Adjunctive Therapy for Cholestatic Pattern

When to Consider Ursodeoxycholic Acid (UDCA)

• For cholestatic drug-induced liver injury (alkaline phosphatase >2× ULN or ALT/AP ratio <2), consider UDCA 13-15 mg/kg/day 1
• UDCA may beneficially affect cholestasis in approximately two-thirds of cases, though evidence is limited 1
• Do not use corticosteroids for cholestatic DILI with normal autoimmune markers and IgG levels 1
• Exception: Consider corticosteroids only if IgG >2× ULN and/or anti-smooth muscle antibody titers >1:80, suggesting drug-induced autoimmune-like hepatitis 1

Critical Monitoring Requirements

Laboratory Surveillance

• Repeat liver function tests within 7-10 days after drug discontinuation to confirm pattern and assess trend 1
• Continue monitoring until alkaline phosphatase normalizes, total bilirubin normalizes, and clinical symptoms resolve 1
• For acetaminophen overdose: check acetaminophen levels, ALT/AST, and INR after last maintenance dose 2
• If acetaminophen levels remain detectable or ALT/AST continue rising, continue N-acetylcysteine beyond 21 hours and contact poison center 2

Exclude Competing Etiologies

• Rule out viral hepatitis (hepatitis A, B, C, D, E), autoimmune hepatitis, biliary obstruction, and ischemic hepatitis 3
• Obtain cross-sectional imaging (CT/MRI) if elevated alkaline phosphatase and/or bilirubin present 3
• Consider MRCP or endoscopic ultrasound for patients with risk factors for biliary obstruction and normal abdominal ultrasound 3

Special Populations and Pitfalls

Patients with Pre-existing Liver Disease

• Higher risk of drug-induced hepatotoxicity in patients with underlying liver disease or previous DILI 4, 6
• Chronic alcohol users have increased risk even if alcohol discontinued during treatment 4
• For cirrhotic patients with decompensation, coordinate treatment with transplant center 3

Common Pitfalls to Avoid

• Do not confuse cholestatic DILI with drug-induced autoimmune-like hepatitis, which presents with elevated aminotransferases >5× ULN, positive autoantibodies, elevated IgG, and may require corticosteroids 1
• Time to biochemical resolution after drug discontinuation may be protracted (mean 14.1 weeks), so do not prematurely restart suspected agents 7, 8
• Most patients (94%) recover completely after withdrawal of the offending drug, with cholestatic injury having better prognosis than hepatocellular injury 1, 8