Predictors of hepatotoxicity among patients treated with antituberculous medication.
BACKGROUND
Hepatotoxicity in patients diagnosed with active tuberculosis (TB) is the commonest adverse effect of therapy. We sought to analyse trends in liver function in patients diagnosed with active TB and to determine predictors of hepatotoxicity.


METHODS
We studied 275 patients with active TB treated at the Mercy University Hospital (Cork, Ireland) from 2009 to 2014 A retrospective review was undertaken of all patients' laboratory data and patient correspondence to determine predictors of hepatotoxicity.


RESULTS
A total of 170 (62%) male and 105 (38%) female patients with active TB with a mean age of 44 years were studied. In total 15 patients (6%) required their medication to be stopped or altered as a consequence of hepatotoxicity. There was a significant difference in age between patients with hepatotoxicity (52.95 years) and those that didn't develop hepatotoxicity (41.33 years) ( P ≤ 0.01). Irish born patients were more likely to develop hepatotoxicity ( P = 0.025). There was no significant association between hepatotoxicity, illicit drug use ( P = 0.211), smoking ( P = 0.95), cavitatory disease ( P = 0.191), site of disease ( p = 0.224), alcohol use ( P = 0.088) or history of alcohol excess ( p = 0.736). Among patients with TB, peak AST values did not occur within the first 2 weeks as widely thought but later (week 10).


CONCLUSIONS
Our study shows hepatotoxicity as a consequence of antituberculous therapy is common. Hepatotoxicity was more common in older patients and Irish born patients, and resulted in drug interruptions and treatment changes. Given the late peak in AST values at week 10 in patients treated with antituberculous therapy, the authors advocate that liver function tests should be monitored regularly throughout the course of treatment.
Department of Respiratory Medicine, Mercy University Hospital, Cork, Ireland.
R P
RP
Cusack
Department of Respiratory Medicine, Mercy University Hospital, Cork, Ireland.
L
L
Chawke
Department of Microbiology, Mercy University Hospital, Cork, Ireland.
D J
DJ
O'Brien
Department of Respiratory Medicine, Mercy University Hospital, Cork, Ireland.
B
B
O'Connor
Department of Respiratory Medicine, Mercy University Hospital, Cork, Ireland.
T M
TM
O'Connor
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D007494:Ireland; D008099:Liver / Q000187:drug effects*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D014376:Tuberculosis / Q000097:blood / Q000188:drug therapy*; D005723:gamma-Glutamyltransferase / Q000097:blood
D000995:Antitubercular Agents; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin