Hepatotoxicity of antituberculosis drugs.

Abstract

We read with interest the editorial by Dr Hall (April 1996;51:351-

Monitoring and management of antituberculosis drug induced hepatotoxicity

“…Reintroduction in the setting of fulminant hepatitis is usually considered unsafe. 25 With the help of close monitoring of symptoms and LFT in the present study, it was possible in these patients to reintroduce antitubercular therapy.…”

“…This was in contrast to the guidelines given by the BTS, where sequential reintroduction of gradually increasing doses at intervals of 2–3 days was suggested 4,9 . The period of 2–3 days was considered insufficient for the identification of the offending drug 25 . The lack of recurrence of ATT‐hepatotoxicity on the reintroduction might be suggestive of the phenomenon of metabolic adaptation 12 .…”

“…Icteric hepatitis is associated with adverse prognosis and has a mortality rate of 4–20% in the absence of liver transplantation 8,17 , 18 . Symptoms of hepatitis develop late in acute hepatic necrosis and are often accompanied by established liver failure 25 . The factor of the greatest clinical importance for development of severe hepatotoxicity and mortality is probably continuation of ATT, once hepatic dysfunction has occured 23,26 .…”

“…8,17,18 Symptoms of hepatitis develop late in acute hepatic necrosis and are often accompanied by established liver failure. 25 The factor of the greatest clinical importance for development of severe hepatotoxicity and mortality is probably continuation of ATT, once hepatic dysfunction has occured. 23,26 Biochemical abnormalities generally occur well before clinical symptoms/signs of hepatic injury are obvious.…”

“…4,9 The period of 2-3 days was considered insufficient for the identification of the offending drug. 25 The lack of recurrence of ATThepatotoxicity on the reintroduction might be suggestive of the phenomenon of metabolic adaptation. 12 Potent induction of the cytochrome p450 (CYP) enzyme system by R is thought to be responsible for enhanced hepatotoxicity of the combination of H and R, but chronic CYP2E1 over-expression results in an adaptive response in the hepatocytes leading to sustained signal-regulated kinase (ERK) activation mediated by EGFR/c-Raf signaling.…”