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Medical Treatment of Vanishing Bile Duct Syndrome in Adults
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
C. Squarcia Giussani, Andrea Crosignani, Mauro Podda
Vanishing bile duct syndrome leads to liver cirrhosis and its complications, and ultimately to liver failure and deaths. The treatment of VBDS should be also aimed at halting or, at least, at slowing the progression of the underlying liver disease. In more advanced stages of VBDS, when the large majority of bile ducts has been destroyed, there is no indication for medical management and the only therapeutic option remains OLT.
Hepatotoxicity of FDA-approved small molecule kinase inhibitors
Published in Expert Opinion on Drug Safety, 2021
Haochen Jiang, Ying Jin, Hao Yan, Zhifei Xu, Bo Yang, Qiaojun He, Peihua Luo
Vanishing bile duct syndrome (VBDS) can be a chronic form of hepatotoxicity that describes acquired and progressive loss of small bile ducts in the liver, leading to cholestasis [37–39]. The condition is largely idiosyncratic and is related to a variety of etiologies. Both VBDS and severe hepatotoxicity associated with vanishing have been reported. In a case report of VBDS following pexidartinib and paclitaxel, evidence suggested that VBDS was relevant to pexidartinib combined with paclitaxel. Moreover, the substantial accessible safety data on paclitaxel implied that paclitaxel was not the cause, but the possibility of the combination was reserved [37]. There are limited data regarding the optimal treatment and prognosis of VBDS. Patients with evidence of bile duct loss on biopsy had significantly higher mortality rates and risk for develop cholestatic chronic liver injury, and supportive treatment is generally used to focus on reducing symptoms associated with prolonged cholestasis.
Antitubercular drugs induced liver injury: an updated insight into molecular mechanisms
Published in Drug Metabolism Reviews, 2023
Drug-induced bile duct obstruction, commonly called cholestasis, leads to impairment of liver function. Several drugs are reportedly causing cholestasis and consequently, bile duct toxicity (Kolarić et al. 2019). Diagnosing cholestatic DILI is a challenging task due to a lack of biomarkers, differential diagnosis, and variability in clinical presentation, which includes disruption in bile acid homeostasis, cholestasis, cholestatic hepatitis, secondary sclerosing cholangitis, and vanishing bile duct syndrome (Sundaram and Björnsson 2017). Bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2) are involved in bile acid transport and bilirubin efflux (Halilbasic et al. 2013). INH + RIF administration decreases BSEP expression in rats (He et al. 2020). Similarly, the farnesoid X receptor (FXR) also regulates the synthesis, excretion, and transport of bile acid (Sinal et al. 2000). Qu et al. (2018) found decreased expression of BSEP and MRP2 could play a significant role in INH-induced liver injury via the sirtuin 1 (SIRT1) and FXR pathways in rats and HepG2 cells. INH + RIF treatment upregulates the expression of MRP2 in rats due to a sustained oxidative stress insult responsible for the transfer of GSSG excretion into bile (Zhang et al. 2016). PZA treatment caused a 10-fold increase in the bile acid level in the serum of rats. PZA administration downregulates the expression of bile acid transport markers such as FXR, BSEP, MRP2, organic solute transporter alpha/beta, organic anion transporting polypeptide (Oatp) 1a1, Oatp1b2, and Cyp8b1 and upregulates the MRP3, Na+-taurocholate cotransporting polypeptide, Cyp7a1, and Oatp1a4 expressions. PZA induces cholestatic liver injury by FXR inhibition, leading to dysfunction in bile acid synthesis and transport (Guo et al. 2016).