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Current Hepatology Reports

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Open Access 26-02-2024 | Pruritus

Cholestatic Pruritus: Pathophysiology, Current Management Approach, and Emerging Therapies

Authors: Vishwajit Kode, Kidist K. Yimam

Published in: Current Hepatology Reports | Issue 1/2024

Abstract

Purpose of Review

Cholestatic pruritus refers to the sensation of itch experienced by patients with disease processes impairing bile flow. This article aims to illustrate the burden of cholestatic pruritus, review the proposed mechanisms, and summarize its available and emerging therapies.

Recent Findings

Pruritus is experienced by many patients with cholestatic liver diseases. It is underdiagnosed and negatively impacts patients’ quality of life. Its direct cause remains unclear though multiple pathways have been explored. Current therapies are insufficient but newly approved ileal bile acid transporter (IBAT) inhibitors and emerging peroxisome proliferator-activated receptor (PPAR) agonists are promising.

Summary

Cholestatic pruritus affects many patients with cholestatic liver diseases and can be debilitating. In moderate to severe cases, current guidelines provide treatment options that are ineffective. Emerging agents such as IBAT inhibitors and PPAR agonists should be considered, including referral to clinical trials. Further exploration into the pathophysiology and effective therapeutic agents is needed.

Tajiri K, Shimizu Y. Recent advances in the management of pruritus in chronic liver diseases. World J Gastroenterol. 2017;23(19):3418–26. https://doi.org/10.3748/wjg.v23.i19.3418. PMID: 28596678; PMCID: PMC5442078CrossRefPubMedPubMedCentral

Younossi ZM, Bernstein D, Shiffman ML, Kwo P, Kim WR, Kowdley KV, Jacobson IM. Diagnosis and management of primary biliary cholangitis. Am J Gastroenterol. 2019;114(1):48–63. https://doi.org/10.1038/s41395-018-0390-3.CrossRefPubMed

van Munster KN, Dijkgraaf MGW, Oude Elferink RPJ, Beuers U, Ponsioen CY. Symptom patterns in the daily life of PSC patients. Liver Int. 2022;42(7):1562–70. https://doi.org/10.1111/liv.15271. Epub 2022 Apr 18. PMID: 35396817; PMCID: PMC9325051CrossRefPubMedPubMedCentral

Mayo MJ, Carey E, Smith HT, Mospan AR, McLaughlin M, Thompson A, Morris HL, Sandefur R, Kim WR, Bowlus C, Investigators TARGET-PBC, Levy C. Impact of pruritus on quality of life and current treatment patterns in patients with primary biliary cholangitis. Dig Dis Sci. 2023;68(3):995–1005. https://doi.org/10.1007/s10620-022-07581-x. Epub 2022 Jun 15CrossRefPubMed

Kamath BM, Baker A, Houwen R, Todorova L, Kerkar N. Systematic review: the epidemiology, natural history, and burden of alagille syndrome. J Pediatr Gastroenterol Nutr. 2018;67(2):148–56. https://doi.org/10.1097/MPG.0000000000001958. PMID: 29543694; PMCID: PMC6110620CrossRefPubMedPubMedCentral

Mighiu C, O'Hara S, Ferri Grazzi E, Murray KF, Schattenberg JM, Ventura E, Karakaidos M, Taylor A, Brrang H, Dhawan A, Willemse J, Finnegan A. Impact of progressive familial intrahepatic cholestasis on caregivers: caregiver-reported outcomes from the multinational PICTURE study. Orphanet J Rare Dis. 2022;17(1):32. https://doi.org/10.1186/s13023-022-02177-0. PMID: 35109890; PMCID: PMC8809495CrossRefPubMedPubMedCentral

Smith HT, de Souza AR, Thompson AH, McLaughlin MM, Dever JJ, Myers JA, Chen JV. Cholestatic pruritus treatments in primary biliary cholangitis and primary sclerosing cholangitis: a systematic literature review. Dig Dis Sci. 2023;68(6):2710–30. https://doi.org/10.1007/s10620-023-07862-z. Epub 2023 Mar 18. PMID: 36933112; PMCID: PMC10024020CrossRefPubMedPubMedCentral

Vander Does A, Levy C, Yosipovitch G. Cholestatic itch: our current understanding of pathophysiology and treatments. Am J Clin Dermatol. 2022;23(5):647–59. https://doi.org/10.1007/s40257-022-00710-2. Epub 2022 Jul 28CrossRefPubMed

Varadi DP. Pruritus induced by crude bile and purified bile acids. Experimental production of pruritus in human skin. Arch Dermatol. 1974;109(5):678–81.CrossRefPubMed

10.

Crosignani A, Del Puppo M, Longo M, De Fabiani E, Caruso D, Zuin M, Podda M, Javitt NB, Kienle MG. Changes in classic and alternative pathways of bile acid synthesis in chronic liver disease. Clin Chim Acta. 2007;382:82–8.CrossRefPubMed

11.

Staels B, Fonseca VA. Bile acids and metabolic regulation: mechanisms and clinical responses to bile acid sequestration. Diabetes Care. 2009;32(Suppl 2(Suppl 2)):S237–45. https://doi.org/10.2337/dc09-S355. PMID: 19875558; PMCID: PMC2811459CrossRefPubMedPubMedCentral

12.

Stiehl A. Bile acids and bile acid sulfates in the skin of patients with cholestasis and pruritus. Z Gastroenterol. 1974;12(2):121–4.PubMed

13.

Alemi F, Kwon E, Poole DP, Lieu T, Lyo V, Cattaruzza F, et al. The TGR5 receptor mediates bile acid-induced itch and analgesia. J Clin Invest. 2013;123(4):1513–30. https://doi.org/10.1172/JCI64551.CrossRefPubMedPubMedCentral

14.

Patel SP, Vasavda C, Ho B, Meixiong J, Dong X, Kwatra SG. Cholestatic pruritus: emerging mechanisms and therapeutics. J Am Acad Dermatol. 2019;81(6):1371–8. https://doi.org/10.1016/j.jaad.2019.04.035. Epub 2019 Apr 19. PMID: 31009666; PMCID: PMC7825249CrossRefPubMedPubMedCentral

15.

Xu J, Wang Y, Khoshdeli M, Peach M, Chuang JC, Lin J, Tsai WW, Mahadevan S, Minto W, Diehl L, Gupta R, Trauner M, Patel K, Noureddin M, Kowdley KV, Gulamhusein A, Bowlus CL, Huss RS, Myers RP, et al. IL-31 levels correlate with pruritus in patients with cholestatic and metabolic liver diseases and is farnesoid X receptor responsive in NASH. Hepatology. 2023;77(1):20–32. https://doi.org/10.1002/hep.32599. Epub 2022 Jul 17. PMID: 35686937; PMCID: PMC9970017CrossRefPubMed

16.

Kabashima K, Irie H. Interleukin-31 as a clinical target for pruritus treatment. Front Med (Lausanne). 2021;12(8):638325. https://doi.org/10.3389/fmed.2021.638325. PMID: 33644103; PMCID: PMC7906974CrossRef

17.

Geraldo LHM, Spohr TCLDS, Amaral RFD, et al. Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies. Signal Transduct Target Ther. 2021;6:45. https://doi.org/10.1038/s41392-020-00367-5.CrossRefPubMedPubMedCentral

18.

Kremer AE, Martens JJ, Kulik W, Ruëff F, Kuiper EM, van Buuren HR, van Erpecum KJ, Kondrackiene J, Prieto J, Rust C, Geenes VL, Williamson C, Moolenaar WH, Beuers U, Oude Elferink RP. Lysophosphatidic acid is a potential mediator of cholestatic pruritus. Gastroenterology. 2010;139(3):1008–18, 1018.e1.CrossRefPubMed

19.

Kittaka H, Uchida K, Fukuta N, Tominaga M. Lysophosphatidic acid-induced itch is mediated by signalling of LPA₅ receptor, phospholipase D and TRPA1/TRPV1. J Physiol. 2017;595(8):2681–98. https://doi.org/10.1113/JP273961. Epub 2017 Mar 22. PMID: 28176353; PMCID: PMC5390871CrossRefPubMedPubMedCentral

20.

Omari SA, Adams MJ, Geraghty DP. TRPV1 Channels in immune cells and hematological malignancies. Adv Pharmacol. 2017;79:173–98. https://doi.org/10.1016/bs.apha.2017.01.002. Epub 2017 Mar 21CrossRefPubMed

21.

Guimaraes MZP, Jordt SE. TRPA1 : A sensory channel of many talents. In: Liedtke WB, Heller S, editors. TRP ion channel function in sensory transduction and cellular signaling cascades. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. Chapter 11. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5237/.

22.

Bujak JK, Kosmala D, Szopa IM, Majchrzak K, Bednarczyk P. Inflammation, cancer and immunity-implication of TRPV1 channel. Front Oncol. 2019;16(9):1087. https://doi.org/10.3389/fonc.2019.01087. sCrossRef

23.

Kong WL, Peng YY, Peng BW. Modulation of neuroinflammation: role and therapeutic potential of TRPV1 in the neuro-immune axis. Brain Behav Immun. 2017;64:354–66. https://doi.org/10.1016/j.bbi.2017.03.007. Epub 2017 Mar 22CrossRefPubMed

24.

Kremer AE, van Dijk R, Leckie P, Schaap FG, Kuiper EM, Mettang T, Reiners KS, et al. Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions. Hepatology. 2012;56(4):1391–400.CrossRefPubMed

25.

Leckie P, Tritto G, Mookerjee R, Davies N, Jones D, Jalan R. ‘Out-patient’ albumin dialysis for cholestatic patients with intractable pruritus. Aliment Pharmacol Ther. 2012;35(6):696–704. https://doi.org/10.1111/j.1365-2036.2012.04994.x. Epub 2012 Jan 20CrossRefPubMed

26.

Langedijk JAGM, Beuers UH, Oude Elferink RPJ. Cholestasis-associated pruritus and its pruritogens. Front Med (Lausanne). 2021;9(8):639674. https://doi.org/10.3389/fmed.2021.639674. PMID: 33791327; PMCID: PMC8006388CrossRef

27.

Bergasa NV. The itch of liver disease. Semin Cutan Med Surg. 2011;30:93–8.CrossRefPubMed

28.

Thornton JR, Losowsky MS. Opioid peptides and primary biliary cirrhosis. BMJ. 1988;297:1501–4.CrossRefPubMedPubMedCentral

29.

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.CrossRefPubMed

30.

Bunchorntavakul C, Reddy KR. Pruritus in chronic cholestatic liver disease. Clin Liver Dis. 2012;16:331–46.CrossRefPubMed

31.

Zagon IS, McLaughlin PJ. Endogenous opioids in the etiology and treatment of multiple sclerosis. In: Zagon IS, McLaughlin PJ, editors. Multiple sclerosis: perspectives in treatment and pathogenesis. Brisbane (AU): Codon Publications; 2017. Chapter 8. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470156/. https://doi.org/10.15586/codon.multiplesclerosis.2017.ch8. Accessed 27 Nov CrossRef

32.

Zagon IS, Wu Y, McLaughlin PJ. Opioid growth factor and organ development in rat and human embryos. Brain Res. 1999;839:313–22.CrossRefPubMed

33.

Pittius CW, Seizinger BR, Mehraein P, Pasi A, Herz A. Proenkephalin-A-derived peptides are present in human brain. Life Sci. 1983;33(Suppl 1):41–4. https://doi.org/10.1016/0024-3205(83)90439-3.CrossRefPubMed

34.

Kim BS, Inan S, Ständer S, Sciascia T, Szepietowski JC, Yosipovitch G. Role of kappa-opioid and mu-opioid receptors in pruritus: Peripheral and central itch circuits. Exp Dermatol. 2022;31(12):1900–7. https://doi.org/10.1111/exd.14669. Epub 2022 Sep 23. PMID: 36054458; PMCID: PMC10087456CrossRefPubMedPubMedCentral

35.

Düll MM, Wolf K, Vetter M, Dietrich P, Neurath MF, Kremer AE. Endogenous opioid levels do not correlate with itch intensity and therapeutic interventions in hepatic pruritus. Front Med (Lausanne). 2021;14(8):641163. https://doi.org/10.3389/fmed.2021.641163. PMID: 33937284; PMCID: PMC8079640CrossRef

36.

Snyder LM, Kuzirian MS, Ross SE. An unexpected role for TRPV4 in serotonin-mediated itch. J Invest Dermatol. 2016;136(1):7–9. https://doi.org/10.1016/j.jid.2015.11.010. PMID: 26763416; PMCID: PMC4758363CrossRefPubMedPubMedCentral

37.

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(12):2736–41.CrossRefPubMed

38.

Schwörer H, Ramadori G. Improvement of cholestatic pruritus by ondansetron. Lancet. 1993;341(8855):1277. https://doi.org/10.1016/0140-6736(93)91178-o.CrossRefPubMed

39.

Yu H, Zhao T, Liu S, Wu Q, Johnson O, Wu Z, Zhuang Z, Shi Y, Peng L, He R, Yang Y, Sun J, Wang X, Xu H, Zeng Z, Zou P, Lei X, Luo W, Li Y. MRGPRX4 is a bile acid receptor for human cholestatic itch. eLife. 2019;8:e48431. https://doi.org/10.7554/eLife.48431.CrossRefPubMedPubMedCentral

40.

Meixiong J, Vasavda C, Green D, Zheng Q, Qi L, Kwatra SG, Hamilton JP, Snyder SH, Dong X. Identification of a bilirubin receptor that may mediate a component of cholestatic itch. eLife. 2019;8:e44116. https://doi.org/10.7554/eLife.44116.CrossRefPubMedPubMedCentral

41.

Beuers U, Kremer AE, Bolier R, Elferink RP. Pruritus in cholestasis: facts and fiction. Hepatology. 2014;60(1):399–407. https://doi.org/10.1002/hep.26909. Epub 2014 May 29CrossRefPubMed

42.

Riaz S, John S. Cholestyramine Resin. [Updated 2022 May 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534089/. Accessed 8 May

43.

Duncan JS, Kennedy HJ, Triger DR. Treatment of pruritus due to chronic obstructive liver disease. Br Med J (Clin Res Ed). 1984;289(6436):22.CrossRefPubMed

44.

Di Padova C, Tritapepe R, Rovagnati P, Rossetti S. Double-blind placebo-controlled clinical trial of microporous cholestyramine in the treatment of intra-and extra-hepatic cholestasis: relationship between itching and serum bile acids. Methods Find Exp Clin Pharmacol. 1984;6(12):773–6.PubMed

45.

Kuiper EM, van Erpecum KJ, Beuers U, Hansen BE, Thio HB, de Man RA, Janssen HL, van Buuren HR. The potent bile acid sequestrant colesevelam is not effective in cholestatic pruritus: results of a double-blind, randomized, placebo-controlled trial. Hepatology. 2010;52(4):1334–40. https://doi.org/10.1002/hep.23821.CrossRefPubMed

46.

Hofmann AF. Rifampicin and treatment of cholestatic pruritus. Gut. 2002;51(5):756–7. https://doi.org/10.1136/gut.51.5.756. PMID: 12377823; PMCID: PMC1773428CrossRefPubMedPubMedCentral

47.

Ghent CN, Carruthers SG. Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double-blind, crossover, randomized trial. Gastroenterology. 1988;94(2):488–93. https://doi.org/10.1016/0016-5085(88)90442-8.CrossRefPubMed

48.

Hague WM, Callaway L, Chambers J, Chappell L, Coat S, de Haan-Jebbink J, Dekker M, Dixon P, Dodd J, Fuller M, Gordijn S, Graham D, Heikinheimo O, Hennessy A, Kaaja R, Khong TY, Lampio L, Louise J, Makris A, et al. A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial. BMC Pregnancy Childbirth. 2021;21(1):51. https://doi.org/10.1186/s12884-020-03481-y. PMID: 33435904; PMCID: PMC7802989CrossRefPubMedPubMedCentral

49.

Ataei S, Kord L, Larki A, Yasrebifar F, Mehrpooya M, Seyedtabib M, Hasanzarrini M. Comparison of sertraline with rifampin in the treatment of cholestatic pruritus: a randomized clinical trial. Rev Recent Clin Trials. 2019;14(3):217–23. https://doi.org/10.2174/1574887114666190328130720.CrossRefPubMed

50.

Podesta A, Lopez P, Terg R, Villamil F, Flores D, Mastai R, Udaondo CB, Companc JP. Treatment of pruritus of primary biliary cirrhosis with rifampin. Dig Dis Sci. 1991;36(2):216–20. https://doi.org/10.1007/BF01300759.CrossRefPubMed

51.

Bachs L, Parés A, Elena M, Piera C, Rodés J. Effects of long-term rifampicin administration in primary biliary cirrhosis. Gastroenterology. 1992;102(6):2077–80. https://doi.org/10.1016/0016-5085(92)90335-v.CrossRefPubMed

52.

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(8):943–8. https://doi.org/10.1111/j.1478-3231.2006.01326.x.CrossRefPubMed

53.

Prince MI, Burt AD, Jones DE. Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary cirrhosis. Gut. 2002;50(3):436–9. https://doi.org/10.1136/gut.50.3.436. PMID: 11839728; PMCID: PMC1773130CrossRefPubMedPubMedCentral

54.

LiverTox: Clinical and research information on drug-induced liver injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Rifampin. [Updated 2018 Jun 10]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548314/. Accessed 10 Jun

55.

Singh D, Saadabadi A. Naltrexone. [Updated 2022 Jun 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534811/. Accessed 30 May

56.

Bergasa NV, Schmitt JM, Talbot TL, Alling DW, Swain MG, Turner ML, Jenkins JB, Jones EA. Open-label trial of oral nalmefene therapy for the pruritus of cholestasis. Hepatology. 1998;27(3):679–84. https://doi.org/10.1002/hep.510270307.CrossRefPubMed

57.

Bergasa NV, Alling DW, Talbot TL, Wells MC, Jones EA. Oral nalmefene therapy reduces scratching activity due to the pruritus of cholestasis: a controlled study. J Am Acad Dermatol. 1999;41(3 Pt 1):431–4. https://doi.org/10.1016/s0190-9622(99)70117-9.CrossRefPubMed

58.

Mansour-Ghanaei F, Taheri A, Froutan H, Ghofrani H, Nasiri-Toosi M, Bagherzadeh AH, Farahvash MJ, Mirmomen S, Ebrahimi-Dariani N, Farhangi E, Pourrasouli Z. Effect of oral naltrexone on pruritus in cholestatic patients. World J Gastroenterol. 2006;12(7):1125–8. https://doi.org/10.3748/wjg.v12.i7.1125. PMID: 16534857; PMCID: PMC4087908CrossRefPubMedPubMedCentral

59.

Terg R, Coronel E, Sordá J, Muñoz AE, Findor J. Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo-controlled study. J Hepatol. 2002;37(6):717–22. https://doi.org/10.1016/s0168-8278(02)00318-5.CrossRefPubMed

60.

Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011;2(4):236–40. https://doi.org/10.4103/2231-4040.90879. PMID: 22247890; PMCID: PMC3255347CrossRefPubMedPubMedCentral

61.

Corpechot C, Chazouillères O, Rousseau A, Le Gruyer A, Habersetzer F, Mathurin P, Goria O, Potier P, Minello A, Silvain C, Abergel A, Debette-Gratien M, Larrey D, Roux O, Bronowicki JP, Boursier J, de Ledinghen V, Heurgue-Berlot A, Nguyen-Khac E, et al. A placebo-controlled trial of bezafibrate in primary biliary cholangitis. N Engl J Med. 2018;378(23):2171–81. https://doi.org/10.1056/NEJMoa1714519.CrossRefPubMed

62.

de Vries E, Bolier R, Goet J, Parés A, Verbeek J, de Vree M, Drenth J, van Erpecum K, van Nieuwkerk K, van der Heide F, Mostafavi N, Helder J, Ponsioen C, Oude Elferink R, van Buuren H, Beuers U. Netherlands Association for the Study of the Liver-Cholestasis Working Group. Fibrates for Itch (FITCH) in fibrosing cholangiopathies: a double-blind, randomized, placebo-controlled trial. Gastroenterology. 2021;160(3):734–743.e6. https://doi.org/10.1053/j.gastro.2020.10.001. Epub 2020 Oct 5CrossRefPubMed

63.

Dyson JK, Jeffreys Jones DE. Bezafibrate for the treatment of cholestatic pruritus: time for a change in management? Gastroenterology. 2021;160(3):649–51. https://doi.org/10.1053/j.gastro.2020.12.019. Epub 2020 Dec 16CrossRefPubMed

64.

Grigorian AY, Mardini HE, Corpechot C, Poupon R, Levy C. Fenofibrate is effective adjunctive therapy in the treatment of primary biliary cirrhosis: a meta-analysis. Clin Res Hepatol Gastroenterol. 2015;39(3):296–306. https://doi.org/10.1016/j.clinre.2015.02.011. Epub 2015 Apr 14CrossRefPubMed

65.

Schattenberg JM, Pares A, Kowdley KV, Heneghan MA, Caldwell S, Pratt D, Bonder A, Hirschfield GM, Levy C, Vierling J, Jones D, Tailleux A, Staels B, Megnien S, Hanf R, Magrez D, Birman P, Luketic V. A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA. J Hepatol. 2021;74(6):1344–54. https://doi.org/10.1016/j.jhep.2021.01.013. Epub 2021 Jan 21CrossRefPubMed

66.

Kowdley KV, Bowlus CL, Levy C, Akarca US, Alvares-da-Silva MR, Andreone P, Arrese M, Corpechot C, Francque SM, Heneghan MA, Invernizzi P, Jones D, Kruger FC, Lawitz E, Mayo MJ, Shiffman ML, Swain MG, Valera JM, Vargas V, et al. Efficacy and safety of elafibranor in primary biliary cholangitis. N Engl J Med. 2023; https://doi.org/10.1056/NEJMoa2306185. Epub ahead of print

67.

Kouno T, Liu X, Zhao H, Kisseleva T, Cable EE, Schnabl B. Selective PPARδ agonist seladelpar suppresses bile acid synthesis by reducing hepatocyte CYP7A1 via the fibroblast growth factor 21 signaling pathway. J Biol Chem. 2022;298(7):102056. https://doi.org/10.1016/j.jbc.2022.102056. Epub 2022 May 20. PMID: 35605662; PMCID: PMC9214809CrossRefPubMedPubMedCentral

68.

Jones D, Boudes PF, Swain MG, Bowlus CL, Galambos MR, Bacon BR, Doerffel Y, Gitlin N, Gordon SC, Odin JA, Sheridan D, Wörns MA, Clark V, Corless L, Hartmann H, Jonas ME, Kremer AE, Mells GF, Buggisch P, et al. Seladelpar (MBX-8025), a selective PPAR-δ agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study. Lancet Gastroenterol Hepatol. 2017;2(10):716–26. https://doi.org/10.1016/S2468-1253(17)30246-7. Epub 2017 Aug 14CrossRefPubMed

69.

Bowlus CL, Galambos MR, Aspinall RJ, Hirschfield GM, Jones DEJ, Dörffel Y, Gordon SC, Harrison SA, Kremer AE, Mayo MJ, Thuluvath PJ, Levy C, Swain MG, Neff GW, Sheridan DA, Stanca CM, Berg CP, Goel A, Shiffman ML, et al. A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis. J Hepatol. 2022;77(2):353–64. https://doi.org/10.1016/j.jhep.2022.02.033. Epub 2022 Mar 30CrossRefPubMed

70.

Hirschfield GM, Shiffman ML, Gulamhusein A, Kowdley KV, Vierling JM, Levy C, Kremer AE, Zigmond E, Andreone P, Gordon SC, Bowlus CL, Lawitz EJ, Aspinall RJ, Pratt DS, Raikhelson K, Gonzalez-Huezo MS, Heneghan MA, Jeong SH, Ladrón de Guevara AL, et al. Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study. Hepatology. 2023;78(2):397–415. https://doi.org/10.1097/HEP.0000000000000395. Epub 2023 Apr 6. PMID: 37386786; PMCID: PMC10344437CrossRefPubMed

71.

Hirschfield GM, Bowlus CL, Kremer AE, RESPONSE Study Group. Efficacy and safety of seladelpar in patients with primary biliary cholangitis in the response trial: a phase 3 international, randomized, placebo-controlled study. Poster presented at. Boston, Ma, USA: AASLD; 2023.

72.

Al-Dury S, Wahlström A, Wahlin S, Langedijk J, Elferink RO, Ståhlman M, Marschall HU. Pilot study with IBAT inhibitor A4250 for the treatment of cholestatic pruritus in primary biliary cholangitis. Sci Rep. 2018;8(1):6658. https://doi.org/10.1038/s41598-018-25214-0. PMID: 29704003; PMCID: PMC5923243ADSCrossRefPubMedPubMedCentral

73.

Loomes KM, Squires RH, Kelly D, Rajwal S, Soufi N, Lachaux A, Jankowska I, Mack C, Setchell KDR, Karthikeyan P, Kennedy C, Dorenbaum A, Desai NK, Garner W, Jaecklin T, Vig P, Miethke A, Thompson RJ. Maralixibat for the treatment of PFIC: long-term, IBAT inhibition in an open-label, Phase 2 study. Hepatol Commun. 2022;6(9):2379–90. https://doi.org/10.1002/hep4.1980. Epub 2022 May 4. PMID: 35507739; PMCID: PMC9426380CrossRefPubMedPubMedCentral

74.

Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz Ö, Fischler B, Gonzalès E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, et al. Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2022;7(9):830–42. https://doi.org/10.1016/S2468-1253(22)00093-0. Epub 2022 Jul 1CrossRefPubMed

75.

Levy C, Kendrick S, Bowlus CL, Tanaka A, Jones D, Kremer AE, Mayo MJ, Haque N, von Maltzahn R, Allinder M, Swift B, MM ML, Hirschfield GM, GLIMMER Study Group. GLIMMER: a randomized phase 2b dose-ranging trial of linerixibat in primary biliary cholangitis patients with pruritus. Clin Gastroenterol Hepatol. 2023;21(7):1902–1912.e13. https://doi.org/10.1016/j.cgh.2022.10.032. Epub 2022 Nov 4CrossRefPubMed

76.

Mirum Pharmaceuticals. A study to evaluate efficacy and safety of an investigational drug named volixibat in patients with itching caused by primary sclerosing cholangitis (PSC) (VISTAS). NCT04663308. NIH ClincalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04663308 (2020, accessed 6 March 2023)

77.

Orfali RL, Aoki V. Blockage of the IL-31 Pathway as a potential target therapy for atopic dermatitis. Pharmaceutics. 2023;15(2):577. https://doi.org/10.3390/pharmaceutics15020577. PMID: 36839897; PMCID: PMC9961325CrossRefPubMedPubMedCentral

78.

Andreas K, Marlyn M, Gideon H. Seladelpar treatment resulted in correlated decreases in serum il-31 and pruritus in patients with primary biliary cholangitis (PBC): post-hoc results from the phase 3 randomized, placebo-controlled ENHANCE study. Poster presented at. Vienna, Austria: EASL Congress; 2023.

79.

Düll MM, Kremer AE. Newer approaches to the management of pruritus in cholestatic liver disease. Curr Hepatol Rep. 2020a;19(2):86–95. https://doi.org/10.1007/s11901-020-00517-x.CrossRef

80.

Warren JE, Blaylock RC, Silver RM. Plasmapheresis for the treatment of intrahepatic cholestasis of pregnancy refractory to medical treatment. Am J Obstet Gynecol. 2005;192:2088–208.CrossRefPubMed

81.

Cr G, Malinchoc M, Wr K, Rw E, Rh W, Jl P, et al. Quality of life before and after liver transplantation for cholestatic liver disease. Hepatology. 1999;29:356–64.CrossRef

Title: Cholestatic Pruritus: Pathophysiology, Current Management Approach, and Emerging Therapies
Authors: Vishwajit Kode
Kidist K. Yimam
Publication date: 26-02-2024
Publisher: Springer US
Keywords: Pruritus
Primary Biliary Cholangitis
Primary Sclerosing Cholangitis
Bezafibrate
Published in: Current Hepatology Reports / Issue 1/2024
Electronic ISSN: 2195-9595
DOI: https://doi.org/10.1007/s11901-024-00638-7

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