Metabolic Comorbidities and Risk of Development and Severity of Drug-Induced Liver Injury

Table 1

Overview of host metabolism factors influencing specific mechanisms.

Mechanistic factors	Host metabolism factors	Host responses
Threshold dose	High body fat	Reduce drug clearance
Covalent binding	Alcohol, diet	Inducers/inhibitors of drug; metabolizing enzymes
Oxidative stress	Obesity/insulin resistance/NAFLD,; advanced cellular senescence	Increase cellular; oxidants
	Fatty liver	Increase lipid peroxidation
	Obesity/insulin resistance/; NAFLD, nutrition	Depletion of antioxidants
Mitochondrial; liability	Advanced cellular senescence (insulin resistance/NASH, chronic; inflammation)	Mitochondrial; dysfunction
Hepatic; transporters; inhibition	Altered hepatic FXR(e.g., NASH )	Hepatic transporter; regulations
Inflammation and; immune responses	Increased influx of LPS (e.g.,; alcohol abuse), obesity	Proinflammatory Conditions influence inflammation and immune response
Tissue injury and repair	Altered FXR, nutritional deficiencies	Influence tissue repair