DRUG-INDUCED CHRONIC LIVER DISEASE

Abstract

Over the past half-century, major strides have been made in the understanding of disease susceptibility, pathogenesis, and therapy. As a result, many new drugs have either replaced or been added to the vast array of existing medications available for the treatment of disease. Because the liver is the primary site of metabolism and biotransformation, it is not surprising that drug-induced hepatic injury is relatively common. Indeed, it has long been known that a number of widely used and generally well-tolerated drugs can cause acute liver injury. Chronic drug-induced liver disease (injury lasting more than 3 months), by contrast, was first described in the 1950s with the identification of a prolonged cholestatic illness related to chlorapromazine use.70 Since that time, several other drugs have been implicated in the cause of chronic hepatic injury. Efforts to accurately define the frequency and spectrum of drug-induced chronic liver disease faces several obstacles. On the one hand, many drugs may cause clinically inapparent liver injury. As a consequence, estimates of the true incidence of drug-induced liver disease may be falsely low. On the other hand, case reports in the literature tend to focus on the most severe or fatal drug-related reactions, creating the impression of a falsely elevated drug-associated morbidity and mortality. Lastly, the potential for drugs to cause liver injury must take into account the intrinsic or predictable ability of the drug to produce injury (e.g., via toxins) as well as host susceptibility factors that may lead to unpredictable injury. Taking these factors into account, recent data suggest that drug-induced liver injury occurs in approximately 1 in 600 to 1 in 3500 hospital admissions.28 Two percent to 5% of hospital admissions for jaundice in the United States are drug-induced, as are between 15% to 30% of instances of fulminant hepatic failure, and 20% to 50% of cases of nonviral chronic hepatitis.26, 28, 41, 55 At present, 500 to 1000 agents have been implicated in the cause of a broad spectrum of liver diseases.32, 103, 120