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Intrahepatic Cholestasis of Pregnancy
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
ICP is associated with a rise in conjugated bile salts, particularly the tauroconjugates of cholic and chenodeoxycholic acid. Bile acids are the end product of hepatic cholesterol metabolism. The metabolic demand of pregnancy increases the demand for and exceeds hepatic capacity for cholesterol metabolism in susceptible individuals. Bile acids such as glycocholic and taurocholic acid increase in serum and cause itching [7]. Bile acids are inherently cytotoxic and thus their metabolism is tightly regulated. In ICP the transport of bile salts from liver to the gallbladder and intestine is disrupted, leading to compensatory transport of bile salts from hepatocytes into the blood [9]. An increase in bile acid serum concentration is thought to play a primary role in the onset of the typical cholestatic pruritus [8]; however, the correlation between the bile acid serum concentration and severity of pruritus is poor. Moreover, the increased passage of bile acids through the placental barrier appears to be toxic for the fetus during ICP [2].
Improvement of cholestatic episodes in patients with benign recurrent intrahepatic cholestasis (BRIC) treated with rifampicin. A long-term follow-up
Published in Scandinavian Journal of Gastroenterology, 2023
Holmfridur Helgadottir, Geir Folvik, Mette Vesterhus
In recent years, the available genetic testing has made the diagnosis of BRIC easier and growth in the number of case reports has attributed to raised awareness. Mutations in the ATPB81 gene is also associated with predisposition to other cholestatic diseases, such as intrahepatic cholestasis of pregnancy and drug-induced liver injury [29,30]. Hence, detailed characterizations of treatment effects on cholestasis and cholestatic pruritus in patients with BRIC may contribute to improved understanding of the mechanisms associated with cholestasis in general and can have implications for future treatment of more common cholestatic disorders, eventually leading to new therapeutic options. The long follow-up over more than 10 years is a strength of our report; however, a larger sample population with longer follow-up is warranted to confirm our observations.
Current and promising therapy for primary biliary cholangitis
Published in Expert Opinion on Pharmacotherapy, 2019
Andrea A Gossard, Keith D. Lindor
Management of the condition may also require treatment of pruritus. It is estimated that up to 70% of patients with PBC suffer from pruritus at some point [48]. Common therapies include anion-exchange resins such as cholestyramine and colestipol (Table 2). This particular therapeutic approach has been a mainstay of cholestatic pruritus management for approximately 5 decades [49]. The recommended dosage is 4–16 g per day taken with food. Once therapeutic benefit is derived, the dose can be stabilized or reduced. Caution should be exercised to ensure other medicines are avoided 1 h prior and 4 h following the administration of cholestyramine as absorption may be impacted. In the event the dosage is increased to the maximum recommended and symptoms persist after 2 weeks, alternative treatment approaches may be considered.
Novel drugs for the treatment of chronic pruritus
Published in Expert Opinion on Investigational Drugs, 2018
Manuel P. Pereira, Sonja Ständer
Ileal bile acid transporter inhibitors are innovative drugs being tested for CP arising from cholestatic conditions such as primary biliary cholangitis. CP in cholestatic pruritus arises from the accumulation of pruritogenic mediators including bile acids, and therefore, bile acid transporter inhibitors may provide relief. In a phase II, RCT patients with primary biliary cholangitis receiving an ileal bile acid transporter inhibitor (GSK2330672) twice daily (45 mg day 1–3/90 mg day 4–14) for 14 days reported a significant reduction in itch intensity compared to placebo. These results should be regarded with caution since the anti-pruritic effect was analyzed as a secondary outcome in this study [65]. A dose-response study (20–180 mg/day) with itch intensity as the primary endpoint is currently recruiting patients (NCT02966834). Another ileal bile acid transporter inhibitor, A4250, showed promising anti-pruritic effects (0.75–1.5 mg/day for 4 weeks) in patients with cholestatic pruritus due to primary biliary cholangitis [66] and future trials with this drug are planned. Other RCTs with ileal bile acid transporter inhibitors for other cholestatic conditions such as progressive familial intrahepatic cholestasis, and Alagille syndrome are underway.