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Hepatobiliary Diseases

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Pruritus

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Abstract

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.

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Abbreviations

(N)AFLD:

(Non-)alcoholic fatty liver disease

5-HT:

Serotonin

ATX:

Autotaxin

CAR:

Constitutive androstane receptor

CYP3A4:

Cytochrom P450 Monooxygenases, e.g. 3A4

DCA:

Deoxycholic acid

ENPP:

Ectonucleotide pyrophosphatase

FXR:

Farnesoid X receptor

GPCR:

G protein-coupled receptor

ICP:

Intrahepatic cholestasis of pregnancy

LCA:

Lithocholic acid

LPA:

Lysophosphatidic acid

MARS:

Molecular Adsorbent Recirculating System

(N)ASH:

(Non-)alcoholic steatohepatitis

OCA:

Obeticholic acid

PAR-2:

Protease-activated receptor 2

PBC:

Primary biliary cholangitis

PSC:

Primary sclerosing cholangitis

PXR:

Pregnane X receptor

QoL:

Quality of Life

UDCA:

Ursodeoxycholic acid

UV-B:

Ultraviolet light B

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Authors and Affiliations

  1. Department of Medicine 1, Gastroenterology, Hepatology, Pneumology and Endocrinology, Friedrich-Alexander-University of Erlangen, Erlangen, Germany

    Wiebke Pirschel & Andreas E. Kremer MD, PhD

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  1. Wiebke Pirschel
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  2. Andreas E. Kremer MD, PhD
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Correspondence to Andreas E. Kremer MD, PhD .

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Editors and Affiliations

  1. Department of Dermatology, University of Brest, Brest, France

    Laurent Misery

  2. Center of Chronic Pruritus, University Hospital Münster, Münster, Nordrhein-Westfalen, Germany

    Sonja Ständer

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Pirschel, W., Kremer, A.E. (2016). Hepatobiliary Diseases. In: Misery, L., Ständer, S. (eds) Pruritus. Springer, Cham. https://doi.org/10.1007/978-3-319-33142-3_34

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