Drug-induced liver injury

Abstract

Despite its low incidence, drug-induced liver injury should be considered in cases of liver injury when all other etiologic factors have been excluded. Over 1,000 different agents have been reported as potential cause. Age is one of the risk factors for the development of drug-induced liver injury, and in most cases old age means increased risk of developing liver injury, but also greater severity of its clinical features. The disease can manifest itself as hepatocellular, cholestatic or mixed injury. Hepatocellular injury is referred to when the isolated ALT elevation is 5-fold above the upper limit of normal or when the ALT/ALP ratio is greater than 5. Likewise, cholestatic injury is characterized by an isolated ALP elevation 2-fold above the upper limit of normal or by the ALT/ALP ratio lower than 2. Mixed injury is characterized by an ALT/ALP ratio between 2 and 5. The presence of jaundice with elevated aminotransferases is associated with poor prognosis. Disease phenotypes include liver enzyme elevations without jaundice, mild cholestasis, fatty liver, acute hepatic necrosis, acute, cholestatic, mixed or chronic hepatitis, sinusoidal obstruction syndrome, nodular regenerative hyperplasia, hepatic adenoma, and hepatocellular carcinoma. As there is no specific diagnostic test, diagnosing is very difficult and based mainly on excluding other possible causes. In patients with suspected drug-induced liver injury the potentially hepatotoxic drug should be discontinued immediately, and patients with severe coagulopathy or encephalopathy should be referred to a liver transplant centre. The rate of recovery of hepatic function upon withdrawal is variable. In many patients, improvement is seen within several hours or days of discontinuing the potentially hepatotoxic drug; however, some individuals can develop a chronic injury.