Anti-tuberculosis medication and the liver: dangers and recommendations in management

Abstract

A An nt ti i--t tu ub be er rc cu ul lo os si is s m me ed di ic ca at ti io on n a an nd d t th he e l li iv ve er r: : d da an ng ge er rs s a an nd d r re ec co om mm me en nd da at ti io on ns s i in n m ma an na ag ge em me en nt t We suggest a protocol for using liver function tests to monitor for liver damage, and give recommendations on what action to take when these become abnormal.

Cytochrome P450 2E1 Genotype and the Susceptibility to Antituberculosis Drug–Induced Hepatitis

“…10,[13][14][15][16][17] Alcohol consumption, advanced age, acetylator status, and existing chronic liver disease have been reported to increase the risk of antituberculosis drug-induced hepatitis. [3][4][5][6][7][8][9][10][11][12][13][14][15] However, the exact mechanism for this hepatotoxicity remains unclear.…”

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15] Metabolic intermediates of isoniazid, instead of isoniazid per se, are incriminated as the cause of hepatotoxicity. 3,4 Therefore, a better understanding of the metabolism of isoniazid may be of help in understanding the mechanisms underlying hepatotoxicity and obviate its occurrence.…”

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15] The incidence of antituberculosis drug-induced hepatitis ranges from 1% to 36%, depending on different regimens and definitions of hepatic injury. [3][4][5][6][7][8][9][10][11][12][13][14][15] This hepatotoxicity is also the most prevalent drug-induced hepatic injury in Taiwan and many other countries, and its associated mortality is not rare. 10,[13][14][15][16][17] Alcohol consumption, advanced age, acetylator status, and existing chronic liver disease have been reported to increase the risk of antituberculosis drug-induced hepatitis.…”

Comprehensive review of anti-tubercular treatment induced liver injury

“…3 About 10-25% people develop abnormalities in liver function tests (LFTs) and 3% develop hepatitis as a result of ATT. 4 …”

Tuberculosis in Germany from 2001 Onwards

“…Andere Autoren haben demgegenüber empfohlen, bei einem Anstieg der Transaminasen über dem Dreifachen der Norm zunächst INH abzusetzen; im Falle einer anschlieûenden Normalisierung der Werte kann es dann wieder eingesetzt werden, andernfalls sollen auch die anderen potenziell hepatotoxischen Antituberkulotika abgesetzt werden [6]. Diese Empfehlung kann durch eine Induktion einiger P-450-Enzyme durch RMP begründet werden, die in der Initialphase zu einem vermehrten Anfall toxischer Metabolite des INH führen, während sich dieser Effekt nach Autoinduktion des RMP-Metabolismus wieder aufhebt [7].…”