Drug-induced cholestasis.
The spectrum of drug-induced cholestasis ranges from 'bland' reversible cholestasis to chronic forms due to the vanishing bile duct syndrome. Agents known for many years to cause cholestasis include estrogens and anabolic steroids, chlorpromazine, erythromycin, and the oxypenicillins; structurally similar congeners of these drugs (tamoxifen, newer macrolides) may also cause cholestasis. Contemporary drugs linked to cholestastic liver injury include ticlopidine, terfenadine, terbinafine, nimesulide, irbesartan, fluoroquinolones, cholesterol-lowering 'statins,' and some herbal remedies (greater celandine, glycyrrhizin, chaparral). Amoxillin-clavulanate, ibuprofen, and pediatric cases of the vanishing bile duct syndrome are recent additions to a long list of drugs associated with the vanishing bile duct syndrome. Particular human leukocyte antigen profiles have recently been identified among those who have developed cholestasis with specific drugs (tiopronin and amoxicillin-clavulanate), and the mechanistic relevance of these genetic associations is being explored. The treatment of drug-induced cholestasis is largely supportive. The offending drug should be withdrawn immediately. Cholestyramine or ursodeoxycholic acid are used to alleviate pruritus, with rifampicin and opioid antagonists being reserved for those who fail first line therapy. Nutritional support is essential for those with prolonged cholestasis, a subgroup who are at risk of developing biliary cirrhosis and liver failure. Timely referral for liver transplant assessment is crucial in these patients.
Chitturi
S
S
Storr Liver Unit, Westmead Millennium Institute, University of Sydney, Westmead Hospital, New South Wales, Australia.
Farrell
G C
GC
D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002779:Cholestasis / Q000139:chemically induced* / Q000175:diagnosis*; D003937:Diagnosis, Differential; D003875:Drug Eruptions / Q000175:diagnosis* / Q000209:etiology*; D004917:Erythromycin / Q000009:adverse effects*; D006801:Humans; D008297:Male
D000900:Anti-Bacterial Agents; D004917:Erythromycin