19th May 2025

Clinical features

There are no diagnostic tests or biomarkers for DILI. It therefore relies upon the identification of exposure to a drug which precedes the onset of liver injury, exclusion of alternative causes of liver pathology, and an improvement in markers of liver injury on cessation of the drug. Drug rechallenge is generally not advised due to the risk of associated morbidity and mortality. Recreational drugs and herbal and complementary medicines must be considered.

Clinical manifestations

Nearly three quarters of cases of DILI present with jaundice. The clinical spectrum of DILI includes:

• Asymptomatic, mild liver test abnormalities
• Significant elevation in liver enzymes with clinical features of acute hepatitis (malaise, abdominal pain, nausea and vomiting, jaundice, dark urine, pale stools)
• Cholestasis, with clinical features seen in acute hepatitis plus pruritus
• ALF; evidence of coagulopathy and hepatic encephalopathy may be present.
• Chronic liver disease with progression to cirrhosis 
• Chronic liver injury resembling autoimmune hepatobiliary disease; elevated serum markers of autoimmunity are seen e.g. raised anti-nuclear antibody.

A significant proportion of patients with DILI are asymptomatic. Some groups of patients develop signs of a hypersensitivity reaction, with fever and rash, and in some cases Stevens-Johnson syndrome, the mortality of which is higher than in patients without these features.

Histopathological findings

Liver biopsy may be useful to exclude alternative aetiologies for abnormal liver function. In the case of DILI, non-specific findings such as portal neutrophils and intra-hepatocellular cholestasis are seen. 

If other tests for alternative causes of liver injury are negative and the patient has been exposed to a drug known to be associated with liver injury in other patients, liver biopsy may not be necessary. 

Serological testing

As mentioned, there are no serological tests or biomarkers specific to DILI. 

Patients with DILI who meet at least one of the following criteria are deemed to have ‘clinically significant’ liver injury: 

• AST or ALT >5x ULN or ALP >2x ULN, on at least two occasions
• Bilirubin > 2.g mg/dL in association with raised AST, ALT or ALP 
• INR > 1.5 with raised AST, ALT or ALP

Modified Hy’s law states that patients with DILI with serum bilirubin 2 or more times greater than the ULN is associated with increased mortality, and drugs demonstrating this phenomenon within clinical trials are at high risk of causing DILI when introduced to a wider population. 

In cases of idiosyncratic DILI, AST in the realm of 18 times ULN and AST to ALT ratio greater than 1.5 indicates significant risk of progression to ALF.

Radiographic findings

Imaging studies are useful in DILI to exclude venous outflow obstruction as an alternative cause of liver injury.  If there is evidence of cholestasis, imaging can also help to exclude obstruction within the biliary tree.