Current
pharmacotherapy options of
drug-induced liver injury (DILI) remain under discussion and are now evaluated in this analysis. Needless to say, the use of the offending
drug must be stopped as soon as DILI is suspected. Normal dosed drugs may cause idiosyncratic DILI, and drugs taken in overdose commonly lead to intrinsic DILI. Empirically used but not substantiated regarding efficiency by randomized controlled trials (RCTs) is the intravenous
antidote treatment with
N-acetylcysteine (NAC) in patients with intrinsic DILI by
N-acetyl-p-aminophenol (
APAP) overdose. Good data recommending
pharmacotherapy in idiosyncratic DILI caused by hundreds of different drugs are lacking. Indeed, a recent analysis revealed that just eight RCTs have been published, and in only two out of eight trials were DILI cases evaluated for causality by the worldwide used Roussel Uclaf Causality Assessment Method (RUCAM), representing overall a significant methodology flaw, as results of DILI RCTs lacking RUCAM are misleading since many DILI cases are known to be attributable erroneously to nondrug alternative causes. In line with these major shortcomings and mostly based on anecdotal reports,
glucocorticoids (GCs) and other immuno-suppressants may be given empirically in carefully selected patients with idiosyncratic DILI exhibiting autoimmune features or caused by
immune checkpoint inhibitors (ICIs), while some patients with cholestatic DILI may benefit from
ursodeoxycholic acid use; in other patients with
drug-induced hepatic
sinusoidal obstruction syndrome (HSOS) and coagulopathy risks, the indication for
anticoagulants should be considered. In view of many other mechanistic factors such as the hepatic microsomal
cytochrome P450 with a generation of
reactive oxygen species (ROS), ferroptosis with toxicity of intracellular
iron, and modification of the gut microbiome, additional
therapy options may be available in the future. In summation, stopping the offending
drug is still the first line of
therapy for most instances of acute DILI, while various
therapies are applied empirically and not based on good data from RCTs awaiting further trials using the updated RUCAM that asks for strict exclusion and inclusion details like liver injury criteria and provides valid causality rankings of probable and highly probable grades.