Drug-induced liver injury (DILI) typically manifests as an acute hepatitis or acute cholestasis pattern on liver biopsy. Some drugs may also show features of steatohepatitis or vascular injury (e.g., nodular regenerative hyperplasia). Although DILI is not a common cause of chronic hepatitis or chronic cholangiopathy, increasing evidence indicates that some drugs can present with autoimmune hepatitis (AIH)–like hepatitis or chronic cholangiopathy mimicking primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC).

Drug-induced autoimmune-like hepatitis (formerly termed drug-induced AIH) shares many features with classical AIH. Autoantibodies, interface hepatitis, and plasma cell aggregates are commonly observed. The most reliable discriminator between drug-induced autoimmune-like hepatitis and classical AIH is the presence or absence of relapse after withdrawal of immunosuppressive therapy. Histologically, advanced fibrosis (e.g., Ishak stage ≥4) favours classical AIH. Only 10–20 drugs are known to cause AIH-like hepatitis; commonly implicated agents in current practice include nitrofurantoin, minocycline, tetracycline, statins and infliximab.

Long-term recreational use of ketamine causes diffuse biliary injury, and ketamine-associated cholangiopathy is a great mimicker of PSC. It is characterised by diffuse narrowing of the intrahepatic bile ducts, with histological features of chronic cholangiopathy, periductal fibrosis or bile duct loss.

Checkpoint inhibitor–induced liver injury is now well recognised. Whereas liver biopsy was previously performed mainly for diagnostic purposes, current indications include treatment resistance (lack of response to immunosuppression) and suspected biliary involvement. Histologically, checkpoint inhibitor–induced liver injury typically shows panlobular hepatitis or confluent necrosis with prominent CD8-positive T lymphocytes. Cases with checkpoint inhibitor–induced cholangitis may demonstrate PBC-like cholangitis, PSC-like periductal fibrosis, or florid ductular reactions secondary to large-duct obstruction. As approximately 20% of cases show no abnormalities on MRCP, liver biopsy is useful when biliary involvement is suspected.