Clinical Infectious Diseases 2006;42:346-355
This article is in the public domain, and no copyright is claimed.
1058-4838/2006/4203-0007


MAJOR ARTICLE


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

Kashef Ijaz,1 John A. Jereb,1 Lauren A. Lambert,1 William A. Bower,2 Philip
R. Spradling,1 Peter D. McElroy,1 Michael F. Iademarco,1 Thomas R. Navin,1
and Kenneth G. Castro1


No copy rights were attached to this Alan and I found it negatively
interesting...Love to you and good health in 2006. I am in LA and leave today
for home. former Ane, S.Tara Balduf


1Division of Tuberculosis Elimination, National Center for HIV, STD, and TB
Prevention, and 2Division of Viral Hepatitis, National Center for Infectious
Diseases, Centers for Disease Control and Prevention, US Department of
Health and Human Services, Atlanta, Georgia




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, 1773
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.

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