Incidence of and risk factors for severe liver toxicity in HIV-infected patients on anti-tuberculosis treatment.
OBJECTIVE
To assess the incidence and risk factors for severe liver toxicity in human immunodeficiency virus (HIV) infected patients on anti-tuberculosis treatment and the impact of patients' characteristics and concomitant medications instituted during the first week of antituberculosis treatment.


METHODS
HIV-infected patients referred to six French hospitals between 1 January 1992 and 31 December 2004, with confirmed or 'presumptive' tuberculosis (TB). Liver toxicity was studied during the first 2 months of TB treatment.


RESULTS
During the 12 years of the study period, 144 patients were enrolled. Severe liver toxicity developed in 15 (10.7%). The median time to development of liver toxicity was 14 days. In the univariate analysis, high baseline bilirubin levels (P = 0.004), CD4 cell counts between 50 and 100 cells/mm3 (P = 0.022) and the use of fluconazole (P = 0.0005) were associated with liver toxicity. In the multivariate analysis, independent risk factors were abnormal baseline alanine aminotransferase (ALT) (P = 0.028) and bilirubin levels (P = 0.033) and the use of fluconazole (P = 0.008).


CONCLUSIONS
Severe liver toxicity is frequent, and occurs early in the course of anti-tuberculosis treatment. ALT and bilirubin levels should be closely monitored during the first month of treatment, especially in patients with high baseline ALT or bilirubin levels. We suggest caution when prescribing fluconazole and anti-tuberculosis drugs concomitantly, although this needs to be confirmed and further investigated.
Pukenyte
E
E
Department of Infectious Diseases, Centre Hospitalier de Tourcoing, Tourcoing, France. evelina_pukenyte@yahoo.com
Lescure
F X
FX
Rey
D
D
Rabaud
C
C
Hoen
B
B
Chavanet
P
P
Laiskonis
A P
AP
Schmit
J L
JL
May
T
T
Mouton
Y
Y
Yazdanpanah
Y
Y
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000453:epidemiology; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000453:epidemiology
D019380:Anti-HIV Agents; D000995:Antitubercular Agents