The study by Schlossberg et al1 in this issue of Infectious Diseases in Clinical Practice is an important contribution to the literature in an area of ongoing controversy. For years, although the treatment guidelines have not recommended routine biochemical monitoring of liver function in the treatment of latent and active tuberculosis,2 the controversy over this recommendation has raged in the background of practicing internists, family physicians, pulmonologists, and infectious disease experts. I am reminded of this every time that I am called by a physician who has a patient with latent or active tuberculosis. The calling or referring physician asks first about the appropriate treatment course. Subsequent to this, the next question is whether I think that the physician should monitor the liver function panel during such therapy. The treatment guidelines recommend monthly clinical evaluations via patient visit, history, and clinical examination.2 In the small yet direct, concise, and convincing study by Schlossberg et al1 from the Philadelphia Department of Public Health, monthly biochemical monitoring of liver function is suggested as a prudent measure to protect patients from asymptomatic yet potentially dangerous antituberculous drug-induced hepatitis. Previous studies referenced by Schlossberg et al1 in their study span the spectrum from absolute recommendations against such biochemical monitoring to studies that are compelling in favor of routine biochemical monitoring. This probably reflects the diverse nature of the patient populations, differing coexistent medical problems, and other factors that influence the likelihood of hepatotoxicity developing in patient receiving antituberculosis therapy.
The protocol followed by the Philadelphia Department of Public Health reflects a common sense approach to monitoring of patients with latent or active tuberculosis who are receiving treatment with 1, 2, or 3 potentially hepatotoxic agents. In current published recommendations, ongoing biochemical monitoring is suggested for patients with regular alcohol intake, concurrent use of hepatotoxic drugs, prior isoniazid intolerance, current injection drug use habits, and concurrent liver disease such as chronic viral hepatitis and for women who are pregnant or in the immediate postpartum period.3 Unfortunately, the recommended monthly clinical evaluation may not identify those patients at risk for drug-induced hepatitis either because the hepatitis may be asymptomatic as in the study by Schlossberg et al1 or because even a detailed history and physical examination may not identify the presence of alcohol use/abuse, injection drug use, or medications that may have unknowingly been prescribed by another treating physician. Patients may also not understand the signs and symptoms of early drug-induced hepatitis. Reports of a high incidence of severe and/or fatal hepatitis due to combined rifampin and pyrazinamide treatment of latent tuberculosis have added further speculation and caution to the use of these drugs in the treatment of active tuberculosis as part of the primary recommended drug regimen for non-drug-resistant active tuberculosis.4
Numerous discussions that I have had with excellent general internists and infectious disease specialists also remind me of their fear for potential legal action taken against them if "clinical evaluations" go awry, and initially, asymptomatic patients, as described in the study by Schlossberg et al,1 go on to develop severe and potentially fatal hepatotoxicity. Several years ago, a highly regarded general internist in our community was treating a patient with latent tuberculosis who developed fatal isoniazid-induced hepatitis with hepatic necrosis despite appropriate routine clinical evaluations as recommended by the Centers for Disease Control and Prevention/Infectious Diseases Society of America guidelines.2 In the law suit that ensued, the patient's family was awarded a huge monetary settlement for negligent care by this physician. As a result of the legal process and malpractice judgment against him, this excellent person/internist was crestfallen and, soon thereafter, quit practicing general internal medicine to become an occupational medicine physician. In my assessment and that of almost all of my colleagues, this was a major loss of a quality general internist to the community as a whole.
Given the medical resources currently available in the United States and given the simplicity of monthly biochemical monitoring, I believe that more and more physicians are now using such monthly monitoring concomitantly with the monthly clinical evaluation to protect the patient and, perhaps, themselves from a medicolegal disaster similar to that endured by the physician referenced above. When one combines the variable patient history issues noted previously with either language communication difficulties or patient misunderstandings about the signs and symptoms of early drug-induced hepatitis and one then adds the potential for 3 commonly used drugs (isoniazid, rifampin, and pyrazinamide) to cause drug-induced hepatitis,3 rationale thought suggests that monthly biochemical monitoring may be not only reasonable but necessary in the ongoing care of patients with latent or active tuberculosis in the United States in the year 2007.
1. Schlossberg D, Pritchett EN, Nnumolu C. Asymptomatic hepatotoxicity in patients treated for tuberculosis and latent tuberculosis. Infect Dis Clin Pract
2. Centers for Disease Control and Prevention. Treatment of tuberculosis, American Thoracic Society, CDC, and Infectious Disease Society of America. MMWR Morb Mortal Wkly Rep
3. Larson AM, Graziani AL. Up To Date 2007. Available at: http://www.uptodate.com
. Web Tag: WEB006-188.8.131.52-638963648C-6. Accessed July 18, 2007.
4. CDC. Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection-United States. MMWR Morb Mortal Wkly Rep