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Antituberculosis Drugs and Hepatotoxicity

Drs. Yew and Leung underscore several issues regarding the hepatotoxicity of antituberculosis medications. The recent ATS Statement was primarily focused on discussion of first-line agents, due to the substantial breadth and length of the document (1). The Statement does also review hepatotoxicity associated with fluoroquinolones and refers to that associated with para-aminosalicylic acid. Given the increasing need for second-line drugs to treat tuberculosis resistant to first-line agents, we agree there is basis for additional study of the former.

We agree with Drs. Yee and Leung that rechallenge with a hepatotoxic agent with rapidly escalating doses may not generally be helpful, since most hepatotoxicity is idiosyncratic and not dose-related. The Statement, like Drs. Yee and Leung's letter, also discourages rechallenge with pyrazinamide after successful reintroduction of isoniazid and rifampin. As discussed in the Statement, rifampin and pyrazinamide are not generally recommended for the treatment of latent tuberculosis infection due to hepatotoxicity of the regimen (1, 2).

Drs. Yee and Leung suggest that the role of routine biochemical monitoring should be re-examined. Studies to assess the optimal monitoring strategy to identify and prevent hepatotoxicity are needed, as discussed in the Statement. Identification of factors that increase the risk of hepatotoxicity should prompt regular biochemical monitoring, and clinical monitoring should be provided for all treated patients.

Jussi J. Saukkonen, David L. Cohn, Robert M. Jasmer, Steven Schenker, John A. Jereb, Charles M. Nolan, Charles A. Peloquin, Fred M. Gordin, David Nunes, John Bernardo, Raman Venkataramanan and Timothy R. Sterling on behalf of the ATS Hepatotoxicity of Antituberculosis Therapy Subcommittee

FOOTNOTES

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

1. Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, Peloquin CA, Gordin FM, Nunes D, Strader DB, et al., on behalf of the ATS Hepatotoxicity of Antituberculosis Therapy Subcommittee. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006;174:935–952.[Abstract/Free Full Text]
2. Centers for Disease Control and Prevention (CDC); American Thoracic Society. 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, 2003. MMWR Morb Mortal Wkly Rep 2003;52:735–739.[Medline]

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