Understanding Cholestatic Pruritus

A recent review (Hepatology 2014; 60: 399-407) sorts out “facts and fiction” with regard to pruritus in cholestasis.

The authors note that for more than 2000 years there has been a search for the potential pruritogen in cholestasis, “when Aretaeus the Cappadocian (2nd century B.C.) stated that ‘pruritus in jaundiced patients is caused by prickly bilious particles.'”

Key points of review:

Pruritus affects a large number of hepatobiliary diseases

  • Hepatocellular cholestasis: intrahepatic cholestasis of pregnancy (ICP), benign recurrent intrahepatic cholestasis (BRIC), progressive familial intrahepatic cholestasis (PFIC1, PFIC2), Hepatitis C
  • Biliary-liver diseases: primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), PFIC3, Alagille, Drug-induced diseases
  • Obstructive cholestasis: gallstones, IgG4-associated cholangitis, biliary atresia, and other causes

Most recently lysophosphatidic acid LPA) and autotaxin (ATX) have been shown to be important pruritogen candidates in cholestasis

  • “ATX is the main source of circulating LPA levels…In cholestasis, serum ATX activity, but not other putative markers of itch such as serum bile salt levels or serum μ-opiod activity, were correlated with itch intensity.”
  • “Rifampicin was found to reduce ATX expression at the transcriptional level.”  This may explain rifampicin’s efficacy for pruritus in cholestasis.
  • “When the enterohepatic circulation is interrupted by nasobiliary drainage, circulating levels of ATX rapidly dropped concomitant with relief of pruritus.”  So, while ATX is not secreted into bile, other substances in bile, like steroid hormones, like play a role in the induction of ATX.

Current therapeutic recommendations (dosing recommendations provided by authors in Table 3)

  • 1st line: Cholestyramine (except in ICP in which ursodeoxycholic acid is considered 1st line)
  • 2nd line: Rifampicin
  • 3rd line: naltrexone
  • 4th line: sertraline
  • Experimental: ondansetron, phenobarbitol, propranolol, lidocaine, dronabinol, butorphanol, phototherapy, nasobiliary drainage, plasmapharesis (and similar treatments), biliary diversion
  • Liver transplantation

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

2 thoughts on “Understanding Cholestatic Pruritus

  1. Pingback: Clinical Features of Byler Disease | gutsandgrowth

  2. Pingback: Sertraline and Liver Disease | gutsandgrowth

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