Drug-induced bile duct injury: new agents, new mechanisms

Drug-induced bile duct injury can be caused by a long list of agents. In most cases, damage is because of T-cell-mediated idiosyncratic reactions. Recently, a number of new agents, including not only drugs but also herbal supplements, have been incriminated and new mechanisms of bile duct injury have emerged. This review will focus on these new data.

New members of drug families already known to be responsible for bile duct injury have been incriminated. New players have been identified, such as herbal supplements, like kratom, and recreational drugs, such as ketamine used outside the medical setting. Anticytokine monoclonal antibodies are rarely involved. In contrast, antineoplastic treatments are of growing concern, especially immune checkpoint inhibitors, which induce immune-related adverse effects because of the excessive stimulation of the immune system and its lack of regulation.

Two patterns of bile duct injury are recognized. Drug-induced small-duct cholangiopathies target the smaller bile ducts; acute injuries eventually progress to chronic disease in the form of the vanishing bile duct syndrome. Drug-induced sclerosing cholangitis target large bile ducts, with a protracted chronic course; the onset of symptoms may be delayed after drug discontinuation; potentially severe, life-threatening complications can occur.