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Prince et al described three patients with primary biliary cirrhosis who developed hepatotoxicity when given rifampicin to treat their cholestatic pruritus (Gut 2002;50:436–9). They describe the use of rifampicin as “secondline” treatment of cholestatic pruritus. Firstline therapy is generally considered to be cholestyramine, a bile acid sequestrant. Use of this agent is frequently unsatisfactory because of gastrointestinal side effects, especially constipation. I am writing to summarise new evidence that retention of endogenous bile acids causes cholestatic pruritus, and to call attention to a recent abstract indicating that colesevalem, a new bile acid sequestrant, appears to be more potent than cholestyramine and does not induce constipation.
The view that bile acid retention causes pruritus is a very old one. Varco1 in 1947 noted that biliary drainage reduced pruritus in patients with extrahepatic biliary obstruction and that when bile was fed to patients, their pruritus returned. Huet and colleagues2 reported that biliary drainage improved cholestatic pruritus in patients with intrahepatic cholestasis. Administration of cholestyramine, an anion exchange resin with a strong affinity …
Conflict of interest: Professor Hofmann has served as a paid consultant of GelTex Pharmaceuticals and has received stock options for the purchase of shares in that company.