What is the recommended treatment regimen for extrapulmonary tuberculosis (TB) in patients with hepatic insufficiency?

Treatment of Extrapulmonary Tuberculosis in Patients with Hepatic Insufficiency

For patients with extrapulmonary tuberculosis and hepatic insufficiency, treatment should be tailored based on the severity of liver disease, with regimens containing fewer hepatotoxic agents as liver disease becomes more advanced. 1

Assessment of Liver Disease Severity

• Patients with tuberculosis may have abnormal liver function at baseline due to TB itself, which will typically improve with effective treatment 1
• Fluctuations in liver function tests related to pre-existing liver disease can confound monitoring for drug-induced hepatitis 1
• Expert consultation is strongly advised when treating TB patients with advanced or unstable liver disease 1

Treatment Regimens Based on Liver Disease Severity

Mild Liver Disease

• For patients with mild liver disease, standard 6-month regimens may be used with careful monitoring 1
• Monitor liver function tests more frequently, especially during the first 2 months of treatment 1

Moderate to Advanced Liver Disease

• Treatment options should be selected based on the severity of liver disease: 1

1. Regimen without isoniazid (INH):

   • Initial phase: Rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB)
   • Continuation phase: RIF, EMB, and PZA
   • Duration: 6 months total
   • Note: This regimen still contains two hepatotoxic drugs (RIF and PZA) 1

2. Regimen without pyrazinamide:

   • Initial phase: INH, RIF, and EMB for 2 months
   • Continuation phase: INH and RIF for 7 months
   • Duration: 9 months total 1

3. Regimen with only one hepatotoxic drug (for advanced liver disease):

   • Generally, RIF should be retained if possible
   • Additional agents: EMB, a fluoroquinolone, cycloserine, and injectable agents
   • Duration: 12-18 months depending on disease extent and response 1

4. Regimen with no hepatotoxic drugs (for severe unstable liver disease):

   • May include streptomycin, EMB, a fluoroquinolone, and another second-line oral drug
   • Duration: 18-24 months 1
   • Note: Limited data exists on the effectiveness of such regimens 1

Monitoring During Treatment

• For patients with known chronic liver disease, monitor liver function weekly for two weeks then biweekly for the first two months 1
• Stop treatment if:
  • ALT/AST rises to five times normal
  • Bilirubin level rises
  • Symptoms of hepatotoxicity develop (fever, malaise, vomiting, jaundice) 1

Management of Hepatotoxicity

If hepatotoxicity develops during treatment:

• If the patient is not acutely ill and TB is non-infectious, all drugs can be stopped until liver function normalizes 1
• If the patient is acutely ill or has infectious TB, a non-hepatotoxic regimen (streptomycin and ethambutol) should be used until liver function normalizes 1
• Once liver function normalizes, drugs can be reintroduced sequentially with careful monitoring 1:
  1. Start with INH at 50 mg/day, increasing to 300 mg/day after 2-3 days
  2. Add RIF at 75 mg/day, increasing to full dose over several days
  3. Finally add PZA at 250 mg/day, increasing to full dose

Special Considerations for Extrapulmonary TB

• The principles of treating extrapulmonary TB are the same as for pulmonary TB 1
• A 6-month course is recommended for most forms of extrapulmonary TB 1
• Exception: TB meningitis requires 9-12 months of treatment 1
• Corticosteroids may be added for tuberculous pericarditis or meningitis 1

Important Caveats

• Pyrazinamide is considered the most hepatotoxic of the first-line TB drugs 1, 2
• Patients with underlying liver disease are at higher risk for drug-induced liver injury 2, 3
• Tuberculosis itself can involve the liver and cause abnormal liver function 1, 4
• Antituberculous therapy-induced fulminant hepatic failure, though rare, may require liver transplantation in extreme cases 5