The treatment of tuberculosis in patients with chronic liver disease is challenging, and risks versus benefits must be weighed. Potentially hepatotoxic agents include: isoniazid, pyrazinamide, rifampin, and ethionamide. Streptomycin and ethambutol appear to be free of hepatotoxicity. Active tuberculosis requires therapy in the patient with chronic liver disease, while treatment of latent tuberculosis infection might be deferred if the liver disease is likely to improve with therapy or further follow-up. Active hepatitis and end-stage liver disease are relative contraindications to the use of isoniazid or pyrazinamide for the treatment of latent tuberculosis infection.
The American Thoracic Society and Centers for Disease Control and Prevention (CDC) published recommendations regarding treatment of latent tuberculosis infection in 2000 . Four regimens were recommended for the treatment of latent tuberculosis infection in adults: (1) isoniazid daily or twice weekly for 9 months;( 2) isoniazid daily or twice weekly for 6 months; (3) rifampin/pyrazinamide daily for 2 months or twice weekly for 2-3 months; or (4) ripampin daily for 4 months. The isoniazid daily regimen for 9 months is preferred, based on prospective trials.
Recent reports of fatal and severe hepatotoxicity with the rifampin/pyrazinamide 2-month regimen has led to the further recommendation that this regimen should be used with caution, especially in patients taking other medications that might be hepatotoxic or with a history of alcohol abuse . The American Thoracic Society/CDC recommended that patients who are known to have a chronic liver disease, have risk factors for liver disease, or abuse alcohol should have baseline serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin.
Patients with mild or moderate liver disease who undergo treatment with isoniazid alone or rifampicin alone should be monitored by clinical evaluation and liver tests at least monthly. Most expert recommend that isoniazid should be stopped if a patient's aminotransferase level exceed 3 times the upper limit of normal if associated with symptoms and five times the upper limit of normal in the patient is asymptomatic. There are no recommendations for alternative doses of antituberculosis drugs in patients with liver disease.
- American Thoracic Society, CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Resp Crit Care Med 2000;161:S221-SD247.
- CDC. Update: fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations United States, 2001. MMWR 2001;50:733-735.