Table 1 Phenotypes of Hepatotoxicity

Acute hepatic necrosis

Clinical course resembles an acute, toxic injury to the liver with sudden and precipitous onset, marked elevations in serum aminotransferase (ALT, AST) levels, and early signs of hepatic (or other organ) dysfunction or failure despite minimal or no jaundice. Rapid recovery after withdrawal of the agent is also typical. It is typically caused by a direct hepatotoxin and is usually dose dependent and “expected”, rather than idiosyncratic.

Acute hepatitis

Course of illness resembles acute viral hepatitis with insidious onset, a hepatocellular pattern of injury and jaundice. Illness typically lasts 2 to 4 weeks and ultimately resolves, but severe instances can result in acute liver failure and death.

Cholestatic hepatitis

Course of illness is marked by cholestasis, even early at the time of onset. The liver enzyme pattern is cholestatic with prominence of ALP and bilirubin elevations. The illness can be prolonged.

Mixed hepatocellular-cholestatic hepatitis

Course of DILI is considered “mixed” if features of both hepatocellular and cholestatic injury are present. The liver enzyme pattern is characterized by moderate to marked elevations in ALT, AST and ALP, such that the R ratio ^b is between 2 and 5.

Enzyme elevations without jaundice

The most commonly observed form of DILI is the elevation of ALT, AST or ALP (or all) without jaundice and with minimal or no symptoms.

Bland cholestasis

The course of illness is marked by prominent and typically prolonged jaundice and cholestasis with minimal serum enzyme elevations or evidence of hepatocellular necrosis.

Hepatic steatosis and lactic acidosis

The hallmark of this syndrome is hepatic microvesicular steatosis accompanied by lactic acidosis, with clinical and laboratory features of hepatic failure, such as encephalopathy.

Nonalcoholic fatty liver

Nonalcoholic fatty liver disease and steatohepatitis are well documented but rare forms of DILI. In addition, fatty liver disease is more often chronic than acute even when it is drug induced.

Chronic hepatitis

The course of illness resembles chronic viral hepatitis with serum aminotransferase elevations without jaundice and with mild symptoms if any. ALT and AST levels may fluctuate over time and intermittently fall into the normal range.

Sinusoidal obstruction syndrome

Sinusoidal obstruction syndrome, or veno-occlusive disease, is a distinctive and potentially fatal form of hepatic injury that occurs predominantly, if not only, after drug or toxin exposure.

Nodular regenerative hyperplasia

This condition typically presents with the insidious or unexpected onset of signs or symptoms of portal hypertension in a patient with little evidence of chronic liver disease.

Hepatic adenoma and hepatocellular carcinoma

Tumours of the liver include benign tumours such as hepatic adenomas, and malignant cancers such as hepatocellular carcinoma and cholangiocarcinoma.