Monitoring and management of antituberculosis drug induced hepatotoxicity.
BACKGROUND
Hepatotoxicity to antituberculosis therapy (ATT) poses a major challenge. This often results in inadequate therapy. The risk of fulminant hepatic failure and mortality is high once icteric hepatitis develops. There is no consensus on monitoring protocols and for the reintroduction of ATT.


METHODS
All patients (from the Department of Internal Medicine and Gastroenterology, Jagjivanram Hospital and the Department of Gastroenterology, Bombay Hospital, Mumbai, India) with a diagnosis of tuberculosis, who were to receive ATT during the study period, were included in the present study for prospective periodic laboratory monitoring for the development of hepatotoxicity. Those patients who developed hepatotoxicity formed Group A (n = 21), whereas those who did not develop hepatotoxicity were included in Group C (n = 179). For the purpose of comparison with Group A, all the patients who presented directly with ATT induced hepatotoxicity during the study period were categorized as Group B (n = 24). Group A and B were further studied after normalization of liver functions for sequential reintroduction with therapeutic doses at a weekly interval.


RESULTS
In Group A, 66.6% (14 patients) of the patients were diagnosed in the asymptomatic period. Seven patients had symptomatic hepatitis, but none had icteric illness. There were no mortalities in Group A. In contrast, all the patients in Group B had symptomatic hepatitis (75% icteric hepatitis). There was a mortality rate of 16.6% (four patients). Of the 41 patients from Groups A and B who survived, reintroduction was successful in 38/39 (97.4%). In the remaining two patients who were in Group B, reintroduction was not attempted because of decompensated liver disease.


CONCLUSIONS
Periodic laboratory monitoring is important in detecting hepatotoxicity at an early stage, thereby preventing mortality. Sequential reintroduction is often successful.
Agal
Subhash
S
Department of Gastroenterology, Jagjivanram Hospital, Mumbai, India.
Baijal
Rajiv
R
Pramanik
Snehanshu
S
Patel
Nikhil
N
Gupte
Parijat
P
Kamani
Praful
P
Amarapurkar
Deepak
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality / Q000628:therapy*; D002648:Child; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015994:Incidence; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019233:Retreatment; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents