Severe or fatal liver injury in 50 patients in the United States taking rifampin and pyrazinamide for latent tuberculosis infection.
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.
Ijaz
Kashef
K
Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, GA 30333, USA. kijaz@cdc.gov
Jereb
John A
JA
Lambert
Lauren A
LA
Bower
William A
WA
Spradling
Philip R
PR
McElroy
Peter D
PD
Iademarco
Michael F
MF
Navin
Thomas R
TR
Castro
Kenneth G
KG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000401:mortality*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects*; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D019966:Substance-Related Disorders; D014376:Tuberculosis / Q000188:drug therapy*; D014481:United States
D000995:Antitubercular Agents; D011718:Pyrazinamide; D012293:Rifampin