Journal Article

Severe or Fatal Liver Injury in 50 Patients in the United States Taking Rifampin and Pyrazinamide for Latent Tuberculosis Infection

Kashef Ijaz, John A. Jereb, Lauren A. Lambert, William A. Bower, Philip R. Spradling, Peter D. McElroy, Michael F. Iademarco, Thomas R. Navin and Kenneth G. Castro

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 42, issue 3, pages 346-355
Published in print February 2006 | ISSN: 1058-4838
Published online February 2006 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/499244
Severe or Fatal Liver Injury in 50 Patients in the United States Taking Rifampin and Pyrazinamide for Latent Tuberculosis Infection

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Background. Severe liver injuries were attributed to the rifampin and pyrazinamide (RZ) regimen after it was recommended for treating latent tuberculosis infection. Implicating RZ as the likeliest cause required excluding alternative causes.

Methods. US health departments reported data on patients who died or were hospitalized for liver disease within 1 month after taking RZ for latent tuberculosis infection from October 1998 through March 2004. The circumstances were investigated on site for each case. Illness characteristics, reasons for RZ treatment, doses and frequency of administration of pyrazinamide, monitoring during treatment, and causes of liver injury were determined.

Results. Liver injury was attributable to RZ use for all 50 patients reported, 12 of whom died. For 47 patients, RZ was the likeliest cause of liver injury. The median patient age was 44 years (range, 17–73 years). Thirty-two patients (64%) were male. Seven (16%) of 43 patients tested had hepatitis C virus antibodies, 1 (2%) of 45 had chronic hepatitis B, 3 (14%) of 22 had positive results of HIV serologic tests, 34 (71%) of 48 had alcohol use noted, and 33 (66%) of 50 were taking additional hepatotoxic medications. Six patients, 2 of whom died, had no predictors for liver disease. Patients who died were older (median age, 52 vs. 42 years; P = .08) and took a greater number of other medications (median number of medications, 4 vs. 2; P = .05) than did those who recovered, but these 2 factors were correlated (P < .01). Thirty-one patients (62%) were monitored according to guidelines, 9 of whom died.

Conclusions. RZ was the likeliest cause of most of these liver injuries, some of which were fatal in spite of monitoring. Fatality was predicted by age or use of other medications, but none of the cofactors showed promise as a reliable clinical predictor of severe liver injury.

Journal Article.  4735 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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