Pruritus pp 253-266 | Cite as

Hepatobiliary Diseases

  • Wiebke Pirschel
  • Andreas E. KremerEmail author


Chronic Pruritus is a common symptom in patients with hepatobiliary disorders such as primary biliary cholangitis (PBC), primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy or hereditary pediatric cholestatic disorders and may accompany, although less frequently, almost any other liver disease. Bile salts, progesterone metabolites and endogenous opioids have been controversially discussed as potential pruritogens. For these substances, however, neither a correlation with itch severity nor a causative link could be established. The G protein-coupled receptor for bile salts, TGR5, has been shown to be expressed in dorsal root ganglia and give rise to itch in rodents, albeit upon stimuli with suprapathological concentrations of bile salts. The semisynthetic bile salt obeticholic acid which exerts antipruritic properties in PBC was shown to worsen itch intensity at high dosages. The potent neuronal activator lysophosphatidic acid (LPA) and its forming enzyme, autotaxin (ATX), could recently be identified in serum of patients suffering from cholestatic pruritus. Autotaxin activity correlated with itch intensity and effectiveness of several anti-pruritic therapeutic interventions in cholestatic patients. Thus, the ATX-LPA-axis may represent a key element in the pathogenesis of this agonizing symptom.

Therapeutic options for cholestatic pruritus are limited to a few evidence-based and several experimental medical and interventional therapies. Current guidelines recommend a step-by-step approach using cholestyramine, rifampicin, naltrexone, and sertraline. Still, a considerable part of patients remains unresponsive to these drugs and requires experimental approaches including albumin dialysis, plasmapheresis, phototherapy, or nasobiliary drainage.


Autotaxin Bile salt Cholestasis Itch Liver Lysophosphatidic acid LPA Pruritus 



(Non-)alcoholic fatty liver disease






Constitutive androstane receptor


Cytochrom P450 Monooxygenases, e.g. 3A4


Deoxycholic acid


Ectonucleotide pyrophosphatase


Farnesoid X receptor


G protein-coupled receptor


Intrahepatic cholestasis of pregnancy


Lithocholic acid


Lysophosphatidic acid


Molecular Adsorbent Recirculating System


(Non-)alcoholic steatohepatitis


Obeticholic acid


Protease-activated receptor 2


Primary biliary cholangitis


Primary sclerosing cholangitis


Pregnane X receptor


Quality of Life


Ursodeoxycholic acid


Ultraviolet light B


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Copyright information

© Springer-Verlag London 2016

Authors and Affiliations

  1. 1.Department of Medicine 1, Gastroenterology, Hepatology, Pneumology and EndocrinologyFriedrich-Alexander-University of ErlangenErlangenGermany

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