19th May 2025

DILI classification

DILI can be classified into one of several groups, on the basis of either its clinical manifestations, or the underlying pathophysiological mechanism of hepatotoxicity.

When the classification of DILI is made on the basis of its clinical presentation, three distinct classes emerge: hepatocellular injury, cholestatic injury, or mixed disease. The features of each of these are outlined in the table below. When classifying DILI based on the clinical manifestations, the ‘R’ value is used; this is calculated by the following equation: R = (ALT/ULN)/(ALP/ULN) where ALT = alanine transferase, ALP = alkaline phosphatase, and ULN = upper limit of normal.

Table 5: The Features of DILI

Examples of causes of hepatocellular DILI: diclofenac, fenofibrate, isoniazid, rifampicin, pyrazinamide, disulfiram, minocycline, nitrofurantoin

Examples of causes of cholestatic DILI: co-amoxiclav, cephalosporins, flucloxacillin, terbinafine, erythromycin, chlorpromazine

Examples of causes of mixed DILI: carbamazepine, sulphonamides, lamotrigine, phenytoin

When the pathophysiological mechanism is used to distinguish DILI types, it may be separated into either predictable or unpredictable (i.e. idiosyncratic) types. The majority of cases of DILI are idiosyncratic, with the exception of paracetamol overdose. The differences between predictable and idiosyncratic DILI are summarised in the table. 

Table 6: Predictable and Idiosyncratic DILI

Idiosyncratic DILI can be further subdivided on the basis of the underlying pathophysiology, i.e. immune-mediated vs non-immune mediated. The features of each are outlined in the table below. The lion’s share of instances of idiosyncratic DILI are immune-mediated.

Table 7: Features of Idiosyncratic DILI

Some drugs which result in DILI that does not fit into the above classifications include:

• Amiodarone, methotrexate, valproate, tamoxifen – can induce hepatic steatosis
• Androgens, contraceptive steroids, anti-neoplastic agents – peliosis hepatis (multiple foci of blood-filled cavitations within the hepatic parenchyma). 
• Anabolic steroids – hepatocellular adenomas
• Thiopurine therapy (including azathioprine, mercaptopurine) – nodular regenerating hyperplasia