Acute Liver Failure

Acute liver failure consists of severe liver dysfunction, as evidenced by coagulopathy, jaundice, and encephalopathy, usually in the absence of underlying liver disease.

Paracetamol Toxicity

Paracetamol toxicity is associated with liver damage in dose dependent fashion.

It is compounded in the setting of concomitant starvation ketosis or concurrent infections. Hepatocytes metabolize paracetamol via microsomal cytochrome P450 (CYP450) into non-toxic byproducts. This metabolism pathway via CYP450, specifically cytochrome P450 2E1 (CYP2E1), produces reactive oxygen species, originally thought to be the ultimate cause of liver injury in paracetamol overdose. After recent debunking of that long-standing belief, mitochondrial dysfunction has instead been attributed as the main source of free radicals and oxidative stress in paracetamol hepatotoxicity.

Association with Myopathies

There are up to 6 case reports published of paracetamol induced ALF in the listed myopathies.

Proposed mechanisms of injury-

Glutathione depletion and increased CYP2E1 ac- tivity in relation to relative malnutrition may contribute to increased paracetamol toxicity.

Critically ill patients often receive multiple drugs concurrently, drug interactions at the level of paracetamol metabolism, e.g., induction of CYP2E1 or inhibition of alternative pathways, may contribute to increased toxicity

Patients may be undernourished even though weight for age appropriate, and may be an additional contributing factor