What anti-tuberculosis (TB) regimen is recommended for patients with liver disease?

Antituberculosis Regimens for Patients with Liver Disease

For patients with liver disease, antituberculosis regimens should be tailored based on the severity of hepatic dysfunction, with fewer hepatotoxic drugs used as liver disease becomes more advanced. 1

Treatment Algorithm Based on Liver Disease Severity

Mild Liver Disease (Normal or Minimally Elevated Liver Enzymes)

• Standard 6-month regimen can be used with careful monitoring 1
• Monitor liver function tests at baseline and if symptoms of hepatotoxicity develop 1
• For patients with known chronic liver disease, monitor liver function weekly for two weeks then biweekly for the first two months 1

Moderate Liver Disease (Stable Chronic Liver Disease)

• Regimen without pyrazinamide: Isoniazid, rifampin, and ethambutol for 2 months, followed by 7 months of isoniazid and rifampin 1
• This regimen extends treatment to 9 months but eliminates pyrazinamide, which is often implicated in drug-induced liver injury 1, 2
• Monitor liver function tests every 1-4 weeks for at least the first 2-3 months 1

Advanced Liver Disease (Significant Hepatic Dysfunction)

• Regimen without isoniazid: Rifampin, pyrazinamide, and ethambutol with or without a fluoroquinolone for at least 6 months 1
• While this regimen still includes two potentially hepatotoxic drugs, it maintains the 6-month treatment duration 1

Severe/Unstable Liver Disease (Decompensated Cirrhosis)

• Regimen with minimal hepatotoxicity: Ethambutol combined with a fluoroquinolone (e.g., levofloxacin), cycloserine, and a second-line injectable agent for 18-24 months 1
• Avoid aminoglycosides in patients with severe liver disease due to risk of renal insufficiency and bleeding from injection sites (due to coagulopathy) 1
• An ofloxacin-based regimen without rifampin has shown efficacy with reduced hepatotoxicity in patients with chronic liver disease 3

Monitoring Recommendations

Baseline Assessment

• Check liver function before starting treatment 1
• Screen for hepatitis B and C in patients with risk factors (HIV infection, injection drug use, birth in endemic regions) 1

Ongoing Monitoring

• For patients with normal baseline liver function without pre-existing liver disease: monitor clinically and repeat liver tests if symptoms develop 1
• For patients with pre-existing liver disease: measure serum aminotransferases and bilirubin every 1-4 weeks for at least 2-3 months 1
• Monitor INR periodically in patients with severe hepatic impairment 1

When to Stop Treatment

• Stop rifampin, isoniazid, and pyrazinamide if:
  • ALT/AST rises to five times normal 1
  • Bilirubin rises above normal range 1
  • ALT/AST rises above normal with symptoms of hepatitis 1

Management of Hepatotoxicity

If Hepatotoxicity Develops

• If patient is not acutely ill and TB is non-infectious: stop all drugs until liver function normalizes 1
• If patient is acutely ill or has infectious TB: use non-hepatotoxic drugs like ethambutol and streptomycin (with appropriate monitoring) until liver function normalizes 1

Reintroduction Protocol

• Once liver function normalizes, reintroduce drugs sequentially with careful monitoring 1:
  1. Start isoniazid at 50 mg/day, increasing to 300 mg/day after 2-3 days if no reaction
  2. After 2-3 more days without reaction, add rifampin at 75 mg/day, increasing gradually to full dose
  3. Finally, if needed, add pyrazinamide starting at 250 mg/day and increasing gradually

Special Considerations

• Patients with cirrhosis have a 14-fold increased risk of tuberculosis and higher case-fatality rates 4
• Drug-induced hepatotoxicity risk is increased in patients with chronic hepatitis B, hepatitis C, and cirrhosis 4, 5
• For patients with very advanced liver dysfunction (Child-Pugh score ≥11), consider regimens with no hepatotoxic drugs 4
• Expert consultation is strongly advised when treating TB in patients with advanced liver disease 1, 6

Common Pitfalls to Avoid

• Failing to monitor liver function appropriately in high-risk patients 1
• Not educating patients about symptoms of hepatotoxicity and when to seek medical attention 1
• Using standard regimens without modification in patients with advanced liver disease 1, 4
• Overlooking the potential for drug interactions in patients with liver disease who may be on multiple medications 1