What is the management of Anti-Tuberculosis Treatment (ATT)-induced hepatitis according to National Tuberculosis Elimination Programme (NTEP) guidelines?

Management of ATT-Induced Hepatitis According to NTEP Guidelines

When ATT-induced hepatotoxicity occurs, all hepatotoxic drugs (isoniazid, rifampicin, and pyrazinamide) should be immediately stopped, and patients should be monitored until liver function normalizes before sequential reintroduction of drugs. 1

Monitoring for Hepatotoxicity

Pre-treatment Assessment

• Check baseline liver function before starting ATT
• Identify risk factors: advanced age, female sex, malnutrition, HIV infection, pre-existing liver disease, alcohol use

Monitoring Schedule

• For patients with normal baseline liver function:

  • No routine monitoring required
  • Test liver function if symptoms develop (fever, malaise, vomiting, jaundice, or unexplained deterioration) 2

• For patients with pre-existing liver disease:

  • Weekly monitoring for first 2 weeks
  • Biweekly monitoring for first 2 months
  • Monthly monitoring thereafter 1

Criteria for Diagnosing ATT-Induced Hepatotoxicity

• Stop all hepatotoxic drugs when:
  • AST/ALT ≥5× upper limit of normal in asymptomatic patients
  • AST/ALT ≥3× upper limit of normal in symptomatic patients
  • Bilirubin rises above normal range
  • Patient develops jaundice 1

Management of ATT-Induced Hepatotoxicity

Initial Management

1. Stop all hepatotoxic drugs (isoniazid, rifampicin, and pyrazinamide)
2. Evaluate patient's clinical status:
   • If patient is not unwell and TB is non-infectious: No treatment until liver function normalizes
   • If patient is unwell or sputum smear positive: Use non-hepatotoxic regimen (streptomycin and ethambutol) 2
3. Consider hospitalization for close monitoring in severe cases

Reintroduction Protocol

Once liver function tests normalize, reintroduce drugs sequentially:

1. Isoniazid:

   • Start at 50 mg/day
   • Increase to 300 mg/day after 2-3 days if no reaction
   • Continue for 2-3 more days

2. Rifampicin:

   • Start at 75 mg/day
   • Increase to 300 mg after 2-3 days
   • Increase to full dose (450-600 mg based on weight) after another 2-3 days
   • Continue for 2-3 more days

3. Pyrazinamide:

   • Start at 250 mg/day
   • Increase to full dose gradually if no reaction 2

Alternative Regimens

If a drug cannot be reintroduced due to recurrent hepatotoxicity:

• If pyrazinamide is the cause:

  • Isoniazid and rifampicin for 9 months, with ethambutol for initial 2 months

• If isoniazid cannot be used:

  • Rifampicin, ethambutol, and a fluoroquinolone for 12-18 months

• If rifampicin cannot be used:

  • Isoniazid, ethambutol for 12-18 months 1

Patient Education

Patients should be instructed to:

• Stop medications immediately if experiencing symptoms of hepatotoxicity
• Report symptoms promptly: unexplained anorexia, nausea, vomiting, dark urine, jaundice, fatigue, abdominal pain
• Avoid alcohol during treatment
• Avoid other hepatotoxic medications when possible 1

Special Considerations

• Sequential reintroduction is successful in approximately 97% of cases 3
• Continuing ATT after development of jaundice is associated with high fatality rates 4
• Patients with underlying silent chronic liver disease or HBV infection have significantly higher risk of developing ATT-induced hepatotoxicity 4

Monitoring During Reintroduction

• Daily monitoring of clinical condition and liver function during drug reintroduction
• If hepatotoxicity recurs, permanently discontinue the offending drug and design an alternative regimen