Drug-induced hepatotoxicity

Pharmaceutical preparations, but also herbal products and dietary supplements, are emerging contributors to severe forms of liver disease, with hepatotoxicity ranking as the most frequent cause for acute liver failure. Although acetaminophen intoxication is still the reason for many severe cases of druginduced liver injury, the bulk of hepatic reactions to drugs are idiosyncratic. Indeed, the rarity of this serious adverse event prevents its detection in clinical trials. Therefore, in order to collect reliable data, prospective post-marketing studies are needed, especially with commonly used drugs that have been shown to be associated with drug-induced liver injury. Recently, different databases have described acetaminophen, antibiotics, nonsteroidal anti-inflammatory drugs, and anticonvulsants as being associated with drug-induced liver injury. Clinical presentations of drug-induced liver injury include predominantly a hepatocellular type of damage, yet cholestatic and mixed types are also common, the determinants of the type of damage induced by a given drug being poorly understood. Recent analysis of pooled data has underlined the influence of older age in the cholestatic/mixed expression of the liver injury, as well as the independent association of female gender, older age, aspartate aminotransferase levels/hepatocellular type of damage and high bilirubin levels with the risk of fulminant liver failure/death. In the long-term (proving the patient survives to the initial episode) cholestatic mixed type of damage is more prone to become chronic, while in the hepatocellular pattern the severity is greater, with further likelihood of evolution to cirrhosis. Cardiovascular and central nervous system drugs have been found to be the main groups leading to chronic liver damage. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage, and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide,