Toxic hepatitis

Disease Description (Causes and Symptoms)

• Definition summary: A general term for hepatitis caused by liver cell damage from external substances such as medications, herbal medicines, health functional foods, and inhaled or injected chemicals (toxic hepatitis, drug-induced hepatitis).
• Main causes: Toxic metabolites produced during drug metabolism, immune-mediated reactions (drug-induced autoimmune reactions), overdose (e.g., acetaminophen), and folk remedies or supplements with unclear approval or distribution status.
• Pathophysiology: Direct cellular toxicity occurs during drug metabolism in the liver (particularly the endoplasmic reticulum and mitochondria), or an immune response is triggered, leading to liver cell necrosis and inflammation, cholestasis, and, in severe cases, progression to acute liver failure.
• Common symptoms:
  • May begin without symptoms
  • Fatigue, loss of appetite, nausea and vomiting, abdominal pain (right upper quadrant), fever
  • Jaundice, dark urine, gray stools
  • Skin rash and joint pain (with certain drugs or hypersensitivity reactions)
  • In acetaminophen overdose: gastrointestinal symptoms within hours → worsening after several days with jaundice, hepatic encephalopathy, ascites, etc.
• Diagnostic clues: A temporal association between the medication history and the onset of liver injury, and exclusion of other causes of hepatitis (viral, alcohol-related, autoimmune, etc.). Example of an assessment tool: RUCAM (Roussel Uclaf Causality Assessment Method for drug-induced liver injury).

Treatment Methods

• Immediate discontinuation: The most important step is to immediately discontinue the suspected medication (including prescription drugs, over-the-counter drugs, herbal medicines, and health functional foods).
• Supportive treatment and monitoring:
  • Perform periodic blood tests (ALT/AST, total/direct bilirubin, ALP, GGT, INR, and blood cell counts).
  • Symptom management (nausea and vomiting, pain, itching, etc.) and fluid and electrolyte management.
• Specific antidote:
  • Acetaminophen overdose: N-acetylcysteine (NAC) is the standard antidote (early administration is effective when possible; the timing and route of administration are determined by the physician).
• Immune-mediated or autoimmune-like findings:
  • Steroid treatment may be considered, but the indication and appropriateness are determined by a specialist (considering exclusion of other causes and the risk of infection).
• Severe disease/acute liver failure:
  • If acute liver failure is suspected due to hepatic encephalopathy, elevated INR, rapidly increasing bilirubin, etc., emergency hospitalization and evaluation for liver transplantation are necessary (transplantation should be considered if the prognosis is poor).
• Lifestyle management and follow-up:
  • Avoid alcohol and other hepatotoxic medications.
  • Do not restart the causative medication even after recovery (consider the possibility of cross-reactivity).
  • If necessary, establish a vaccination and medication administration plan after confirming complete recovery of liver function.
• Precautions (during treatment):
  • Refrain from self-treatment (folk remedies or combining multiple products).
  • Regular liver function tests are recommended for those taking hepatotoxic medications such as tuberculosis treatments or anticancer drugs for a prolonged period (e.g., at intervals of several weeks).

Checklist Before an Outpatient Visit (Materials, Information to Record, and Example Questions)

• Materials/documents to prepare:
  • A list of currently taken medications (including prescription drugs, nonprescription drugs, herbal medicines, health functional foods, and herbs/supplements) — indicate the medication name, dose, start date, and discontinuation date
  • Past medical history (liver disease, amount of alcohol use, drug allergies or history of hypersensitivity)
  • Recent blood test results (ALT, AST, ALP, GGT, total/direct bilirubin, INR)
  • A diary of when symptoms began and how they changed (including photos and the date symptoms started)
  • Alcohol use history (frequency and amount)
• Questions that are helpful for patients to prepare in advance for the outpatient visit:
  • When and which medication was first taken? When was the last dose taken?
  • How many days or weeks after taking it did the symptoms begin?
  • Did anyone else have a similar reaction when taking the same medication?
  • Have there recently been any vaccinations, surgeries, or exposures to chemicals (such as at the workplace)?

Examples of General Questions to Ask the Doctor

• How likely is it that this medication (or ingredient) caused damage to my liver?
• What is the prognosis for my current liver condition (the possibility of complete recovery and the risk of long-term liver damage)?
• Which medications, foods, or activities should I avoid in daily life?
• Which tests should I undergo in the future, and at what intervals?

Examples of Condition-Specific Questions

• If I need to take the specific medication I was taking (medication name) again, how will the possibility of using an alternative medication or restarting it be determined?
• What is the safe maximum dose of acetaminophen (or the suspected medication I took), and is it permissible to drink alcohol while taking it?