Drug-induced liver injury types

Table 3.4 Examples of types of drug-induced liver injury and associated drugs...

Vinken M, Maes M, Vanhaecke T, Rogiers V (2013) Drug-induced liver injury mechanisms, types and biomarkers. Curr Med Chem 20(24) 3011-21... 

LeCluyse EL, Alexandre E, Hamilton GA, Viollon-Abadie C, Coon DJ, Jolley S, Richert L (2005) Isolation and culture of primary human hepatocytes. Methods Mol Biol 290 207-229 Lecoeur S, Andre C, Beaune PH (1996) Tienilic acid-induced autoimmune hepatitis anti-liver and-kidney microsomal type 2 autoantibodies recognize a three-site conformational epitope on cytochrome P4502C9. Mol Pharmacol 50 326-333 Lee WM (2003) Drug-induced hepatotoxicity. N Engl J Med 349 474-485 Lee WM, Senior JR (2005) Recognizing drug-induced liver injury ctnrent problems, possible solutions. Toxicol Pathol 33 155-164... 

Adverse drug reactions (ADRs) are a major cause of patient morbidity and a significant cause of patient mortality (Lazarou et al. 1998 Pirmohamed et al. 1998). There are many types of ADRs, affecting every organ in the body (Table 1). However, drug-induced liver injury (DILI) is the most frequent reason for the withdrawal of an approved drug from the market (Temple and Himmel 2002), and it accounts for approximately 50% of all acute liver failure cases (Kaplowitz 2001 Lee 2003 Ostapowicz 2002) and 15% of all liver transplantations in the United States (Russo et al. 2004). 

The reaction is generally a type fV hypersensitivity response involving CD4+ cells, CD8+ cytotoxic lymphocytes and NK, Kupffer, and dendritic cells. Type II hypersensitivities may also sometimes occur. Knowledge of mechanisms underlying idiosyncratic drug-induced liver injury is limited. 

Chemical injuries to the liver depend on the type of toxic agent, the severity of intoxication, and the type of exposure, whether acute or chronic. The six basic types of liver damage are fatty liver, necrois, hepatobiliary dysfuntions, viral-hke hepatitis, and (on chronic exposure) cirrhosis and neoplasia. A number of organic chemicals and drugs induce fatty liver and hver necrosis. 

Hepatitis is an inflammation of the liver and is usually viral in origin however, certain chemicals, usually drugs, can induce a hepatitis that closely resembles that produced by viral infections (Table 14.1). This type of liver injury is not usually demonstrable in laboratory animals and is often manifest only in susceptible individuals. Fortunately, the incidence of this type of disease is very low. 

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