(HEPATOLOGY 2011;) The liver is the central organ responsible for

(HEPATOLOGY 2011;) The liver is the central organ responsible for the selective uptake, metabolism, and excretion Angiogenesis inhibitor of drugs, xenobiotics, and environmental toxins. This essential function predisposes the liver to drug toxicity and is the primary reason for the failure of pharmaceutical agents during drug development. Hepatic drug toxicity is the most common cause of acute fulminant hepatic failure, accounting for more than 50% of cases.1 More than a thousand drugs and herbal remedies have been reported to cause a variety of different liver disorders. However, specific diagnostic markers for drug-induced liver

injury (DILI) are lacking, and convincing cause-and-effect evidence exists for few cases.2 Indeed, establishing causality has been a major hindrance in the understanding

of DILI.3, 4 Cholestatic & mixed cholestatic and hepatocellular injury are two of the most severe manifestations of drug-induced liver disease (DILD),5 and account for close to half of all hepatic drug toxicity in some epidemiologic reports.6 There is increasing evidence that drugs that are excreted by the liver into bile are prime candidates for producing cholestatic liver disease in the susceptible patient.7 Several forms of cholestatic liver injury can be produced by drugs, and these can present acutely or in the form of chronic liver disease. Drug-induced cholestasis may mimic other intrahepatic EPZ-6438 manufacturer and extrahepatic cholestatic diseases. Not recognizing a drug as a triggering factor for cholestasis prolongs exposure to the toxic agent, which may lead to worse liver injury and unnecessary diagnostic and therapeutic

interventions. Acute and chronic cholestatic liver injury results from dysfunction of the mechanisms of bile formation. However, drug-induced cholestasis can present with asymptomatic disease where the only clinical manifestation is an elevation in alkaline phosphatase (AP). Moreover, the target of injury can vary from a mixed hepatocellular cholestatic injury, to impairment of canalicular bile flow resulting in pure intrahepatic cholestasis, or to an “obstructive” drug-induced cholangiopathy where the initial site of injury is located at various levels of the bile duct epithelium.8-10 The incidence and associated health see more care costs secondary to drug-induced cholestasis are not available, in part because most drugs commonly cause asymptomatic cholestasis associated with mild abnormalities in the serum liver profile. A Danish study of 110 cases of DILI from 1978 to 1987 reported a 17% prevalence of acute cholestatic injury.11 In the United States, the prevalence of drug-induced cholestasis was reported to be 20% in the elderly population. However, on examination, not all of these cases included patients with cholestasis.12 Approximately 2%-5% of hospitalized cases with jaundice are caused by drugs but cholestasis is expressed in only some of these patients.

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