Drug-induced liver injury: Review article

Drug-induced liver injury (DILI) is a term that describes abnormalities in liver function tests (LFTs) related to medication intake. DILI, a subtype of hepatotoxicity, does not include hepatic injuries related to nonmedicinal compounds, including herbal, complementary, and alternative medicines [1, 2]. DILI accounts for roughly 0.1% to 3% of hospital admissions, 600 liver transplantations, and 120 deaths from liver failure in the United States each year [3-6]. It is the Number 1 cause of death from acute liver failure in the country [3], and the most frequent cause of medication withdrawal from the market [7]. The liver is the central organ in the metabolism and detoxification of drugs and toxins. Consequently, drugs affect the liver more frequently than any other organ and place the liver at increased risk for toxic damage [8]. After absorption by the intestines, drugs reach the liver via the portal system. In the hepatocytes, these chemicals undergo complex metabolic processes to be converted into hydrophilic substances, readily soluble in the blood stream and easily eliminated thereafter [7]. Drugs or their metabolites can cause toxic effect on the liver. Many of the intermediate metabolites have a short half-life, some estimated to be less than a minute, which makes detecting them a challenging task [9]. Drug-induced liver injuries are idiosyncratic reactions except for acetaminophen and methotrexate, which cause dose-dependent liver injury [4]. Idiosyncratic reactions are unpredictable adverse reactions that usually occur between 5 and 90 days from the initiation of drug usage [7, 10].