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Pruritus pp 253-266 | Cite as

Hepatobiliary Diseases

  • Wiebke Pirschel
  • Andreas E. KremerEmail author
Chapter

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.

Keywords

Autotaxin Bile salt Cholestasis Itch Liver Lysophosphatidic acid LPA Pruritus 

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

References

  1. 1.
    Abu-Hayyeh S, Ovadia C, Lieu T, et al. Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum. Hepatology. 2016;63:1287–98.Google Scholar
  2. 2.
    Akiyama T, Carstens MI, Piecha D, et al. Nalfurafine suppresses pruritogen- and touch-evoked scratching behavior in models of acute and chronic itch in mice. Acta Derm Venereol. 2015;95:147–50.PubMedCrossRefGoogle Scholar
  3. 3.
    Alemi F, Kwon E, Poole DP, et al. The TGR5 receptor mediates bile acid-induced itch and analgesia. J Clin Invest. 2013;123:1513–30.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Bachs L, Pares A, Elena M, et al. Comparison of rifampicin with phenobarbitone for treatment of pruritus in biliary cirrhosis. Lancet. 1989;1:574–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Bachs L, Pares A, Elena M, et al. Effects of long-term rifampicin administration in primary biliary cirrhosis. Gastroenterology. 1992;102:2077–80.PubMedCrossRefGoogle Scholar
  6. 6.
    Ballantyne JC, Loach AB, Carr DB. Itching after epidural and spinal opiates. Pain. 1988;33:149–60.PubMedCrossRefGoogle Scholar
  7. 7.
    Bartholomew TC, Summerfield JA, Billing BH, et al. Bile acid profiles of human serum and skin interstitial fluid and their relationship to pruritus studied by gas chromatography-mass spectrometry. Clin Sci (Lond). 1982;63:65–73.CrossRefGoogle Scholar
  8. 8.
    Batta AK, Salen G, Mirchandani R, et al. Effect of long-term treatment with ursodiol on clinical and biochemical features and biliary bile acid metabolism in patients with primary biliary cirrhosis. Am J Gastroenterol. 1993;88:691–700.PubMedGoogle Scholar
  9. 9.
    Bergasa NV. The pruritus of cholestasis. J Hepatol. 2005;43:1078–88.PubMedCrossRefGoogle Scholar
  10. 10.
    Bergasa NV. The itch of liver disease. Semin Cutan Med Surg. 2011;30:93–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Bergasa NV, Alling DW, Talbot TL, et al. Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial. Ann Intern Med. 1995;123:161–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Bergasa NV, Link MJ, Keogh M, et al. Pilot study of bright-light therapy reflected toward the eyes for the pruritus of chronic liver disease. Am J Gastroenterol. 2001;96:1563–70.PubMedCrossRefGoogle Scholar
  13. 13.
    Bergasa NV, Mehlman JK, Jones EA. Pruritus and fatigue in primary biliary cirrhosis. Baillieres Best Pract Res Clin Gastroenterol. 2000;14:643–55.PubMedCrossRefGoogle Scholar
  14. 14.
    Bergasa NV, Schmitt JM, Talbot TL, et al. Open-label trial of oral nalmefene therapy for the pruritus of cholestasis. Hepatology. 1998;27:679–84.PubMedCrossRefGoogle Scholar
  15. 15.
    Bergasa NV, Talbot TL, Alling DW, et al. A controlled trial of naloxone infusions for the pruritus of chronic cholestasis. Gastroenterology. 1992;102:544–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Bergasa NV, Thomas DA, Vergalla J, et al. Plasma from patients with the pruritus of cholestasis induces opioid receptor-mediated scratching in monkeys. Life Sci. 1993;53:1253–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Beuers U. Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:318–28.PubMedCrossRefGoogle Scholar
  18. 18.
    Beuers U, Gerken G, Pusl T. Biliary drainage transiently relieves intractable pruritus in primary biliary cirrhosis. Hepatology. 2006;44:280–1.PubMedCrossRefGoogle Scholar
  19. 19.
    Beuers U, Kremer AE, Bolier R, et al. Pruritus in cholestasis: facts and fiction. Hepatology. 2014;60:399–407.PubMedCrossRefGoogle Scholar
  20. 20.
    Borgeat A, Wilder-Smith O, Mentha G, et al. Propofol and cholestatic pruritus. Am J Gastroenterol. 1992;87:672–4.PubMedGoogle Scholar
  21. 21.
    Browning J, Combes B, Mayo MJ. Long-term efficacy of sertraline as a treatment for cholestatic pruritus in patients with primary biliary cirrhosis. Am J Gastroenterol. 2003;98:2736–41.PubMedCrossRefGoogle Scholar
  22. 22.
    Cacoub P, Poynard T, Ghillani P, et al. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment virus C. Arthritis Rheum. 1999;42:2204–12.PubMedCrossRefGoogle Scholar
  23. 23.
    Carey EJ, Ali AH, Lindor KD. Primary biliary cirrhosis. Lancet. 2015;386:1565–75.PubMedCrossRefGoogle Scholar
  24. 24.
    Carson KL, Tran TT, Cotton P, et al. Pilot study of the use of naltrexone to treat the severe pruritus of cholestatic liver disease. Am J Gastroenterol. 1996;91:1022–3.PubMedGoogle Scholar
  25. 25.
    Cerio R, Murphy GM, Sladen GE, et al. A combination of phototherapy and cholestyramine for the relief of pruritus in primary biliary cirrhosis. Br J Dermatol. 1987;116:265–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Cevikbas F, Steinhoff M, Ikoma A. Role of spinal neurotransmitter receptors in itch: new insights into therapies and drug development. CNS Neurosci Ther. 2011;17:742–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Chia SC, Bergasa NV, Kleiner DE, et al. Pruritus as a presenting symptom of chronic hepatitis C. Dig Dis Sci. 1998;43:2177–83.PubMedCrossRefGoogle Scholar
  28. 28.
    Cohen LB, Ambinder EP, Wolke AM, et al. Role of plasmapheresis in primary biliary cirrhosis. Gut. 1985;26:291–4.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Combes B, Emerson SS, Flye NL, et al. Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis. Hepatology. 2005;42:1184–93.PubMedCrossRefGoogle Scholar
  30. 30.
    Cribier B, Samain F, Vetter D, et al. Systematic cutaneous examination in hepatitis C virus infected patients. Acta Derm Venereol. 1998;78:355–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Cynamon HA, Andres JM, Iafrate RP. Rifampin relieves pruritus in children with cholestatic liver disease. Gastroenterology. 1990;98:1013–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Datta DV, Sherlock S. Treatment of pruritus of obstructive jaundice with cholestyramine. Br Med J. 1963;1:216–9.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Datta DV, Sherlock S. Cholestyramine for long term relief of the pruritus complicating intrahepatic cholestasis. Gastroenterology. 1966;50:323–32.PubMedGoogle Scholar
  34. 34.
    Decock S, Roelandts R, Steenbergen WV, et al. Cholestasis-induced pruritus treated with ultraviolet B phototherapy: an observational case series study. J Hepatol. 2012;57:637–41.PubMedCrossRefGoogle Scholar
  35. 35.
    EASL Clinical Practice Guidelines. Management of cholestatic liver diseases. J Hepatol. 2009;51:237–67.CrossRefGoogle Scholar
  36. 36.
    Elias E. Liver transplantation. J R Coll Physicians Lond. 1993;27:224–32.PubMedGoogle Scholar
  37. 37.
    Elias E, Burra P. Primary biliary cirrhosis: symptomatic treatment. J Gastroenterol Hepatol. 1991;6:570–3.PubMedCrossRefGoogle Scholar
  38. 38.
    Emerick KM, Whitington PF. Partial external biliary diversion for intractable pruritus and xanthomas in Alagille syndrome. Hepatology. 2002;35:1501–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Freedman MR, Holzbach RT, Ferguson DR. Pruritus in cholestasis: no direct causative role for bile acid retention. Am J Med. 1981;70:1011–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2009;15:2049–66.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Ghent CN, Bloomer JR. Itch in liver disease: facts and speculations. Yale J Biol Med. 1979;52:77–82.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Ghent CN, Bloomer JR, Klatskin G. Elevations in skin tissue levels of bile acids in human cholestasis: relation to serum levels and to pruritus. Gastroenterology. 1977;73:1125–30.PubMedGoogle Scholar
  43. 43.
    Ghent CN, Carruthers SG. Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double-blind, crossover, randomized trial. Gastroenterology. 1988;94:488–93.PubMedCrossRefGoogle Scholar
  44. 44.
    Gittlen SD, Schulman ES, Maddrey WC. Raised histamine concentrations in chronic cholestatic liver disease. Gut. 1990;31:96–9.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Glantz A, Reilly SJ, Benthin L, et al. Intrahepatic cholestasis of pregnancy: amelioration of pruritus by UDCA is associated with decreased progesterone disulphates in urine. Hepatology. 2008;47:544–51.PubMedCrossRefGoogle Scholar
  46. 46.
    Gong Y, Huang Z, Christensen E, et al. Ursodeoxycholic acid for patients with primary biliary cirrhosis: an updated systematic review and meta-analysis of randomized clinical trials using Bayesian approach as sensitivity analyses. Am J Gastroenterol. 2007;102:1799–807.PubMedCrossRefGoogle Scholar
  47. 47.
    Hanid MA, Levi AJ. Phototherapy for pruritus in primary biliary cirrhosis. Lancet. 1980;2:530.PubMedCrossRefGoogle Scholar
  48. 48.
    Hashimoto T, Ohata H, Momose K. Itch-scratch responses induced by lysophosphatidic acid in mice. Pharmacology. 2004;72:51–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Heathcote EJ. Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines. Hepatology. 2000;31:1005–13.PubMedCrossRefGoogle Scholar
  50. 50.
    Huesmann M, Huesmann T, Osada N, et al. Cholestatic pruritus: a retrospective analysis on clinical characteristics and treatment response. J Dtsch Dermatol Ges = J Ger Soc Dermatol: JDDG. 2013;11:158–68.Google Scholar
  51. 51.
    James O, Macklon AF, Watson AJ. Primary biliary cirrhosis – a revised clinical spectrum. Lancet. 1981;1:1278–81.PubMedGoogle Scholar
  52. 52.
    Jones EA, Bergasa NV. The pruritus of cholestasis and the opioid system. JAMA. 1992;268:3359–62.PubMedCrossRefGoogle Scholar
  53. 53.
    Jones EA, Bergasa NV. The pathogenesis and treatment of pruritus and fatigue in patients with PBC. Eur J Gastroenterol Hepatol. 1999;11:623–31.PubMedCrossRefGoogle Scholar
  54. 54.
    Jones EA, Bergasa NV. Evolving concepts of the pathogenesis and treatment of the pruritus of cholestasis. Can J Gastroenterol. 2000;14:33–40.PubMedCrossRefGoogle Scholar
  55. 55.
    Jones EA, Neuberger J, Bergasa NV. Opiate antagonist therapy for the pruritus of cholestasis: the avoidance of opioid withdrawal-like reactions. QJM. 2002;95:547–52.PubMedCrossRefGoogle Scholar
  56. 56.
    Kamei J, Nagase H. Norbinaltorphimine, a selective kappa-opioid receptor antagonist, induces an itch-associated response in mice. Eur J Pharmacol. 2001;418:141–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Kaplan MM, Schmid C, Provenzale D, et al. A prospective trial of colchicine and methotrexate in the treatment of primary biliary cirrhosis. Gastroenterology. 1999;117:1173–80.PubMedCrossRefGoogle Scholar
  58. 58.
    Khurana S, Singh P. Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta-analysis of prospective randomized-controlled trials. Liver Int. 2006;26:943–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Kiefel JM, Cooper ML, Bodnar RJ. Serotonin receptor subtype antagonists in the medial ventral medulla inhibit mesencephalic opiate analgesia. Brain Res. 1992;597:331–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Kirby J, Heaton KW, Burton JL. Pruritic effect of bile salts. Br Med J. 1974;4:693–5.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Kondrackiene J, Beuers U, Kupcinskas L. Efficacy and safety of ursodeoxycholic acid versus cholestyramine in intrahepatic cholestasis of pregnancy. Gastroenterology. 2005;129:894–901.PubMedCrossRefGoogle Scholar
  62. 62.
    Koulentaki M, Ioannidou D, Stefanidou M, et al. Dermatological manifestations in primary biliary cirrhosis patients: a case control study. Am J Gastroenterol. 2006;101:541–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Kremer AE, Beuers U, Oude-Elferink RP, et al. Pathogenesis and treatment of pruritus in cholestasis. Drugs. 2008;68:2163–82.PubMedCrossRefGoogle Scholar
  64. 64.
    Kremer AE, Feramisco J, Reeh PW, et al. Receptors, cells and circuits involved in pruritus of systemic disorders. Biochim Biophys Acta. 1842;2014:869–92.Google Scholar
  65. 65.
    Kremer AE, Martens JJ, Kulik W, et al. Lysophosphatidic acid is a potential mediator of cholestatic pruritus. Gastroenterology. 2010;139:1008–18.PubMedCrossRefGoogle Scholar
  66. 66.
    Kremer AE, Oude Elferink RP, Beuers U. Pathophysiology and current management of pruritus in liver disease. Clin Res Hepatol Gastroenterol. 2011;35:89–97.PubMedCrossRefGoogle Scholar
  67. 67.
    Kremer AE, van Dijk R, Leckie P, et al. Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions. Hepatology. 2012;56:1391–400.PubMedCrossRefGoogle Scholar
  68. 68.
    Kuiper EM, van Erpecum KJ, Beuers U, et al. The potent bile acid sequestrant colesevelam is not effective in cholestatic pruritus: results of a double-blind, randomized, placebo-controlled trial. Hepatology. 2010;52:1334–40.PubMedCrossRefGoogle Scholar
  69. 69.
    LaMotte RH, Dong X, Ringkamp M. Sensory neurons and circuits mediating itch. Nat Rev Neurosci. 2014;15:19–31.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    LaMotte RH, Shimada SG, Sikand P. Mouse models of acute, chemical itch and pain in humans. Exp Dermatol. 2011;20:778–82.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    LeCluyse EL. Pregnane X, receptor: molecular basis for species differences in CYP3A induction by xenobiotics. Chem Biol Interact. 2001;134:283–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Lens S, Leoz M, Nazal L, et al. Bezafibrate normalizes alkaline phosphatase in primary biliary cirrhosis patients with incomplete response to ursodeoxycholic acid. Liver Int: Off J Int Assoc Study Liver. 2014;34:197–203.CrossRefGoogle Scholar
  73. 73.
    Leuschner M, Maier KP, Schlichting J, et al. Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial. Gastroenterology. 1999;117:918–25.PubMedCrossRefGoogle Scholar
  74. 74.
    Lieu T, Jayaweera G, Zhao P, et al. The bile acid receptor TGR5 activates the TRPA1 channel to induce itch in mice. Gastroenterology. 2014;147:1417–28.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med. 1997;336:691–5.PubMedCrossRefGoogle Scholar
  76. 76.
    Lindor KD, Gershwin ME, Poupon R, et al. Primary biliary cirrhosis. Hepatology. 2009;50:291–308.PubMedCrossRefGoogle Scholar
  77. 77.
    Macia M, Aviles J, Navarro J, et al. Efficacy of molecular adsorbent recirculating system for the treatment of intractable pruritus in cholestasis. Am J Med. 2003;114:62–4.PubMedCrossRefGoogle Scholar
  78. 78.
    Mansour-Ghanaei F, Taheri A, Froutan H, et al. Effect of oral naltrexone on pruritus in cholestatic patients. World J Gastroenterol. 2006;12:1125–8.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Marschall HU, Wagner M, Zollner G, et al. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology. 2005;129:476–85.PubMedCrossRefGoogle Scholar
  80. 80.
    Mayo MJ, Handem I, Saldana S, et al. Sertraline as a first-line treatment for cholestatic pruritus. Hepatology. 2007;45:666–74.PubMedCrossRefGoogle Scholar
  81. 81.
    McNeil B, Dong X. Peripheral mechanisms of itch. Neurosci Bull. 2012;28:100–10.PubMedCrossRefGoogle Scholar
  82. 82.
    McPhedran NT, Henderson RD. Pruritus and Jaundice. Can Med Assoc J. 1965;92:1258–60.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Mells GF, Pells G, Newton JL, et al. Impact of primary biliary cirrhosis on perceived quality of life: the UK-PBC national study. Hepatology. 2013;58:273–83.PubMedCrossRefGoogle Scholar
  84. 84.
    Mettang T, Kremer AE. Uremic pruritus. Kidney Int. 2015;87:685–91.PubMedCrossRefGoogle Scholar
  85. 85.
    Moolenaar WH, Perrakis A. Insights into autotaxin: how to produce and present a lipid mediator. Nat Rev Mol Cell Biol. 2011;12:674–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Mudaliar S, Henry RR, Sanyal AJ, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology. 2013;145:574–82.e1.PubMedCrossRefGoogle Scholar
  87. 87.
    Murphy GM, Ross A, Billing BH. Serum bile acids in primary biliary cirrhosis. Gut. 1972;13:201–6.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Neff GW, O’Brien CB, Reddy KR, et al. Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease. Am J Gastroenterol. 2002;97:2117–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Neuberger J, Jones EA. Liver transplantation for intractable pruritus is contraindicated before an adequate trial of opiate antagonist therapy. Eur J Gastroenterol Hepatol. 2001;13:1393–4.PubMedCrossRefGoogle Scholar
  90. 90.
    Ng VL, Ryckman FC, Porta G, et al. Long-term outcome after partial external biliary diversion for intractable pruritus in patients with intrahepatic cholestasis. J Pediatr Gastroenterol Nutr. 2000;30:152–6.PubMedCrossRefGoogle Scholar
  91. 91.
    O’Donohue JW, Pereira SP, Ashdown AC, et al. A controlled trial of ondansetron in the pruritus of cholestasis. Aliment Pharmacol Ther. 2005;21:1041–5.PubMedCrossRefGoogle Scholar
  92. 92.
    Palma J, Reyes H, Ribalta J, et al. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo. J Hepatol. 1997;27:1022–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Pares A, Cisneros L, Salmeron JM, et al. Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis. Am J Gastroenterol. 2004;99:1105–10.PubMedCrossRefGoogle Scholar
  94. 94.
    Pares A, Herrera M, Aviles J, et al. Treatment of resistant pruritus from cholestasis with albumin dialysis: combined analysis of patients from three centers. J Hepatol. 2010;53:307–12.PubMedCrossRefGoogle Scholar
  95. 95.
    Paus R, Schmelz M, Biro T, et al. Frontiers in pruritus research: scratching the brain for more effective itch therapy. J Clin Invest. 2006;116:1174–86.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Podesta A, Lopez P, Terg R, et al. Treatment of pruritus of primary biliary cirrhosis with rifampin. Dig Dis Sci. 1991;36:216–20.PubMedCrossRefGoogle Scholar
  97. 97.
    Poupon RE, Chretien Y, Poupon R, et al. Serum bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid therapy. Hepatology. 1993;17:599–604.PubMedCrossRefGoogle Scholar
  98. 98.
    Prince MI, Burt AD, Jones DE. Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary cirrhosis. Gut. 2002;50:436–9.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Pusl T, Beuers U. Extrahepatic manifestations of cholestatic liver diseases: pathogenesis and therapy. Clin Rev Allergy Immunol. 2005;28:147–57.PubMedCrossRefGoogle Scholar
  100. 100.
    Pusl T, Beuers U. Ursodeoxycholic acid treatment of vanishing bile duct syndromes. World J Gastroenterol. 2006;12:3487–95.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Pusl T, Denk GU, Parhofer KG, et al. Plasma separation and anion adsorption transiently relieve intractable pruritus in primary biliary cirrhosis. J Hepatol. 2006;45:887–91.PubMedCrossRefGoogle Scholar
  102. 102.
    Quist RG, Ton-Nu HT, Lillienau J, et al. Activation of mast cells by bile acids. Gastroenterology. 1991;101:446–56.PubMedCrossRefGoogle Scholar
  103. 103.
    Ramachandran P, Shanmugam NP, Sinani SA, et al. Outcome of partial internal biliary diversion for intractable pruritus in children with cholestatic liver disease. Pediatr Surg Int. 2014;30:1045–9.PubMedCrossRefGoogle Scholar
  104. 104.
    Rautiainen H, Karkkainen P, Karvonen AL, et al. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. Hepatology. 2005;41:747–52.PubMedCrossRefGoogle Scholar
  105. 105.
    Reich A, Stander S, Szepietowski JC. Drug-induced pruritus: a review. Acta Derm Venereol. 2009;89:236–44.PubMedCrossRefGoogle Scholar
  106. 106.
    Reyes H, Sjovall J. Bile acids and progesterone metabolites in intrahepatic cholestasis of pregnancy. Ann Med. 2000;32:94–106.PubMedCrossRefGoogle Scholar
  107. 107.
    Richardson BP. Serotonin and nociception. Ann N Y Acad Sci. 1990;600:511–9.PubMedCrossRefGoogle Scholar
  108. 108.
    Schaap FG, Trauner M, Jansen PL. Bile acid receptors as targets for drug development. Nat Rev Gastroenterol Hepatol. 2014;11:55–67.Google Scholar
  109. 109.
    Schworer H, Hartmann H, Ramadori G. Relief of cholestatic pruritus by a novel class of drugs: 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists: effectiveness of ondansetron. Pain. 1995;61:33–7.PubMedCrossRefGoogle Scholar
  110. 110.
    Sherlock S, Scheuer PJ. The presentation and diagnosis of 100 patients with primary biliary cirrhosis. N Engl J Med. 1973;289:674–8.PubMedCrossRefGoogle Scholar
  111. 111.
    Spivey JR, Jorgensen RA, Gores GJ, et al. Methionine-enkephalin concentrations correlate with stage of disease but not pruritus in patients with primary biliary cirrhosis. Am J Gastroenterol. 1994;89:2028–32.PubMedGoogle Scholar
  112. 112.
    Stander S, Reinhardt HW, Luger TA. Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus. Hautarzt. 2006;57:801–7.PubMedCrossRefGoogle Scholar
  113. 113.
    Stapelbroek JM, van Erpecum KJ, Klomp LW, et al. Nasobiliary drainage induces long-lasting remission in benign recurrent intrahepatic cholestasis. Hepatology. 2006;43:51–3.PubMedCrossRefGoogle Scholar
  114. 114.
    Steinhoff M, Neisius U, Ikoma A, et al. Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. J Neurosci. 2003;23:6176–80.PubMedGoogle Scholar
  115. 115.
    Swain MG. Pruritus and lethargy in the primary billary cirrhosis patient. In: Neuberger J, editor. Primary biliary cirrhosis. Eastbourne: West End Studios; 1999. p. 75–81.Google Scholar
  116. 116.
    Swain MG, Rothman RB, Xu H, et al. Endogenous opioids accumulate in plasma in a rat model of acute cholestasis. Gastroenterology. 1992;103:630–5.PubMedCrossRefGoogle Scholar
  117. 117.
    Talwalkar JA, Lindor KD. Primary biliary cirrhosis. Lancet. 2003;362:53–61.PubMedCrossRefGoogle Scholar
  118. 118.
    Talwalkar JA, Souto E, Jorgensen RA, et al. Natural history of pruritus in primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2003;1:297–302.PubMedCrossRefGoogle Scholar
  119. 119.
    Tandon P, Rowe BH, Vandermeer B, et al. The efficacy and safety of bile Acid binding agents, opioid antagonists, or rifampin in the treatment of cholestasis-associated pruritus. Am J Gastroenterol. 2007;102:1528–36. Epub 2007 Mar 31.PubMedCrossRefGoogle Scholar
  120. 120.
    Terg R, Coronel E, Sorda J, et al. Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo-controlled study. J Hepatol. 2002;37:717–22.PubMedCrossRefGoogle Scholar
  121. 121.
    Thomas DA, Willams GM, Iwata K, et al. Effects of central administration of opioids on facial scratching in monkeys. Brain Res. 1992;1–2:315–7.Google Scholar
  122. 122.
    Thornton JR, Losowsky MS. Opioid peptides and primary biliary cirrhosis. BMJ. 1988;297:1501–4.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Togashi Y, Umeuchi H, Okano K, et al. Antipruritic activity of the kappa-opioid receptor agonist, TRK-820. Eur J Pharmacol. 2002;435:259–64.PubMedCrossRefGoogle Scholar
  124. 124.
    Trauner M, Baghdasaryan A, Claudel T, et al. Targeting nuclear bile acid receptors for liver disease. Dig Dis. 2011;29:98–102.PubMedCrossRefGoogle Scholar
  125. 125.
    Turner IB, Rawlins MD, Wood P, et al. Flumecinol for the treatment of pruritus associated with primary biliary cirrhosis. Aliment Pharmacol Ther. 1994;8:337–42.PubMedCrossRefGoogle Scholar
  126. 126.
    van der Woerd WL, Kokke FT, van der Zee DC, et al. Total biliary diversion as a treatment option for patients with progressive familial intrahepatic cholestasis and Alagille syndrome. J Pediatr Surg. 2015;50:1846–9.PubMedCrossRefGoogle Scholar
  127. 127.
    Villamil AG, Bandi JC, Galdame OA, et al. Efficacy of lidocaine in the treatment of pruritus in patients with chronic cholestatic liver diseases. Am J Med. 2005;118:1160–3.PubMedCrossRefGoogle Scholar
  128. 128.
    Walt RP, Daneshmend TK, Fellows IW, et al. Effect of stanozolol on itching in primary biliary cirrhosis. Br Med J (Clin Res Ed). 1988;296:607.CrossRefGoogle Scholar
  129. 129.
    Weisshaar E, Ziethen B, Gollnick H. Can a serotonin type 3 (5-HT3) receptor antagonist reduce experimentally-induced itch? Inflamm Res. 1997;46:412–6.PubMedCrossRefGoogle Scholar
  130. 130.
    Wikstrom B, Gellert R, Ladefoged SD, et al. Kappa-opioid system in uremic pruritus: multicenter, randomized, double-blind, placebo-controlled clinical studies. J Am Soc Nephrol. 2005;16:3742–7. Epub 2005 Oct 26.PubMedCrossRefGoogle Scholar
  131. 131.
    Wolfhagen FH, Sternieri E, Hop WC, et al. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology. 1997;113:1264–9.PubMedCrossRefGoogle Scholar
  132. 132.
    Yosipovitch G, Bernhard JD. Clinical practice. Chronic pruritus. N Engl J Med. 2013;368:1625–34.PubMedCrossRefGoogle Scholar
  133. 133.
    Yosipovitch G, Greaves MW, Schmelz M. Itch. Lancet. 2003;361:690–4.PubMedCrossRefGoogle Scholar
  134. 134.
    Zylicz Z, Krajnik M, Sorge AA, et al. Paroxetine in the treatment of severe non-dermatological pruritus: a randomized, controlled trial. J Pain Symptom Manag. 2003;26:1105–12.CrossRefGoogle Scholar

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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