6 Nevertheless, a wide variety of commonly used drugs can induce cholestatic liver injury including nonsteroidal anti-inflammatory drugs, antihypertensives, antidiabetics, anticonvulsants, lipid-lowering agents, and psychotropic drugs.11-17 Many drugs target the biliary epithelium and result in drug-induced cholangiopathy and vanishing bile duct syndrome (VBDS). Terms such as “drug-induced bile duct injury” MI-503 purchase and “disappearing intrahepatic bile ducts” are also used to refer

to this type of drug-induced injury that can mimic primary biliary cirrhosis or small duct primary sclerosing cholangitis (PSC).8 A few rare agents such as 2-fluoro 2′-deoxyuridine can also produce injury to the larger bile ducts; in these cases, injury to the hepatic artery must be excluded as ischemia to the biliary epithelium

may result in a similar complication. ABC, ATP-binding cassette; ALT, alanine aminotransferase; ANIT, α-naphthylisothiocyanate; AP, alkaline phosphatase; AST, aspartate aminotransferase; BCRP, breast cancer resistance protein; BSEP, bile salt export pump; CYP, cytochrome P450; DILD, drug-induced liver disease; DILI, drug-induced liver injury; GGT, gamma glutamyl transferase; MDR1, multidrug resistance-1 protein; MRP, multidrug resistance protein; NTCP, sodium-dependent taurocholate cotransporting Dabrafenib in vitro polypeptide; OATP, organic anion transporting polypeptide; PXR, pregnane X receptor; UDCA, ursodeoxycholic acid; VBDS, vanishing bile duct syndrome. Individual drugs that induce drug-induced cholestasis tend to have a characteristic signature, which is composed of a clinical and pathological before pattern, but a single drug can exhibit more than one specific signature. Cholestatic reactions tend to be prolonged after the discontinuation of the causative agent, presumably because cholangiocyte repair and regeneration is slower than that of the hepatocyte, and because bile secretory function may be slower to recover than other hepatocyte functions.

In some cases, persistence of a self-propagating immune response may play a role in prolonging drug-induced cholestasis. Drug-induced cholestasis may present as an acute illness that promptly subsides with the withdrawal of the offending agent. It may present with or without jaundice. However, parenchymal liver injury may elicit nonspecific symptoms such as nausea, malaise, anorexia, and fatigue. Abdominal pain or discomfort may be present in drug-induced cholestasis, especially that caused by amoxicillin–clavulanate or erythromycin.18 Symptoms may occur weeks or months after beginning treatment. Chronic drug-induced cholestasis can result in development of xanthomas, pruritus, and melanoderma.19 Pruritus can be the major reason that patients seek medical care.