Published: 7 September 2023
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Vanishing bile duct syndrome – a complication of drug-induced liver injury
Published: 7 September 2023
Prescriber Update 44(3): 56–57
September 2023
What is vanishing bile duct syndrome (VBDS)?
Bile ducts transport bile from the liver and gallbladder to the small intestine, where the bile helps to break down the fats from food.
VBDS is characterised by progressive destruction and disappearance of the bile ducts (ductopenia) in the liver, which slows or stops the flow of bile (cholestasis).1 VBDS can be diagnosed with a liver biopsy.2 VBDS may lead to a blockage of the bile duct system (biliary obstruction) and permanent liver damage.2
The mechanism behind VBDS is unknown but it can be caused by immune-mediated disorders, cancers, infections and medicines. One suggested mechanism is T-cell-mediated immune dysfunction leading to biliary apoptosis (programmed cell death).2
VBDS is a complication of drug-induced liver injury
Vanishing bile duct syndrome is a rare but serious complication of drug-induced liver injury.3
Antibiotics are most frequently associated with VBDS, although several drug classes and medicines have been implicated. Table 1 lists the most frequently reported medicine classes and medicines associated with VBDS.3
Signs and symptoms of VBDS have been reported one to six months after starting the offending medicine.2 Some patients may be asymptomatic and VBDS is initially identified based on laboratory abnormalities. Other patients may have symptoms of cholestasis, such as persistent pruritus (itching), fatigue and jaundice (yellowing of the skin). Additionally, patients with chronic cholestasis may have skin xanthomas (fatty skin lesions), dyslipidaemia (abnormal fat levels in the blood), and fat-soluble vitamin deficiencies (low levels of vitamins A, D, E and K).2
Patients with VBDS have laboratory test results that are generally consistent with cholestasis (ie, abnormal liver function tests, including elevated serum alkaline phosphatase, total bilirubin and gamma-glutamyl transpeptidase).2
Table 1: Medicine class and medicines most frequently reported to cause vanishing bile duct syndrome
| Medicine class | Medicines |
|---|---|
| Penicillins | Amoxicillin, amoxicillin + clavulanic acid |
| Fluoroquinolones | Ciprofloxacin, moxifloxacin |
| Sulphonamides | Co-trimoxazole (trimethoprim + sulfamethoxazole) |
| Macrolides | Azithromycin |
| Antivirals | Nevirapine |
| Anticonvulsants | Carbamazepine, lamotrigine |
| Rheumatologic agents | Allopurinol |
| Antineoplastic agents | Temozolomide |
| Non-steroidal anti-inflammatories | Ibuprofen |
Note:
List not exhaustive. Table is adapted from the source below to show the most frequently reported medicines that were also approved and available in New Zealand on 3 July 2023.
Source:
Adapted from: National Institute of Diabetes and Digestive Kidney Diseases. 2012. Vanishing bile duct syndrome. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury updated 11 December 2019. URL: www.ncbi.nlm.nih.gov/books/NBK548715/ (accessed 30 June 2023).
Management
Due to its rarity, there is no standardised treatment for VBDS.1 Management can involve supportive measures and monitoring for signs of disease progression and complications of chronic cholestasis. Specialist input may be required.2
VBDS may improve by treating the underlying cause or withdrawing the offending medicine.1
References
- Izzo P, Gallo G, Codacci Pisanelli M, et al. 2022. Vanishing bile duct syndrome in an adult patient: Case report and review of the literature. Journal of Clinical Medicine 11(12): 3253. URL: www.mdpi.com/2077-0383/11/12/3253 (accessed 29 June 2023).
- Reau N. 2023. Hepatic ductopenia and vanishing bile duct syndrome in adults. In: UpToDate 22 February 2023. URL: www.uptodate.com/contents/hepatic-ductopenia-and-vanishing-bile-duct-syndrome-in-adults (accessed 29 June 2023).
- National Institute of Diabetes and Digestive Kidney Diseases. 2012. Vanishing bile duct syndrome. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury updated 11 December 2019. URL: www.ncbi.nlm.nih.gov/books/NBK548715/ (accessed 30 June 2023).
