Drugs that damage the liver

Drugs that damage the liver account for 9.5% of all suspected adverse drug reactions (ADRs), are the main cause of fatal ADRs and are the most common reason for withdrawal of drugs from the market. Pre-market surveillance detects common ADRs, but those seen in clinical practice are rare (1 in 10,000–100,000). Their recognition depends on individual reports and post market surveillance. In the UK, the yellow card scheme is used to report all suspected ADRs with new drugs and serious ADRs with established drugs. Both under-reporting and over-reporting occur. Information on hepatotoxicity, therefore, is neither systematic or comprehensive. The liver is particularly affected as it is the central metabolizing organ through which all foreign compounds pass. Injury may be a direct toxic effect or immunological reaction to either the drug or an active metabolite formed by bio-activation (it was reported that for 62% of withdrawn drugs it is the metabolite that is toxic). Any type of liver injury can be reproduced by drugs and any drug can produce different types of liver injury. Injury may be acute or chronic and there can be adaptation to injurious effects with a transient increase in liver function in patients that have significant ongoing injury. Many factors interact to lead to injury and there is considerable variation in susceptibility which may be inherited and acquired. This contribution focuses on general principles of drug-induced liver disease. Information on specific ADRs can be obtained from the British National Formulary, drug datasheets and databases.