Display options
Share it on

Therap Adv Gastroenterol. 2017 Oct;10(10):791-803. doi: 10.1177/1756283X17728669. Epub 2017 Sep 07.

Novel strategies and therapeutic options for the management of primary biliary cholangitis.

Therapeutic advances in gastroenterology

Amardeep Khanna, David E Jones

Affiliations

  1. Clinical Research Associate, Institute of Cellular Medicine, 4th Floor William Leech Building, Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  2. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

PMID: 29051789 PMCID: PMC5638183 DOI: 10.1177/1756283X17728669

Abstract

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. It has a varied course of progression ranging from being completely asymptomatic to aggressive disease leading to cirrhosis and resulting in liver transplantation. In addition, symptoms can be debilitating and can have a major impact on quality of life. For decades, there was only one anti-cholestatic agent available to target this disease and that was only effective in around half of patients, with little or no effect on symptoms. With increasing understanding of the pathogenic mechanisms of PBC and potential targets for drug treatment, pharmaceutical companies have shown a greater interest in this rare disease. A large number of novel therapeutic molecules have been developed and are currently being evaluated. In this review article all the novel molecules in use and in trials targeting cholestasis and symptoms in PBC are discussed.

Keywords: bile acids; obeticholic acid; primary biliary cholangitis/cirrhosis; ursodeoxycholic acid

Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

References

  1. Gastroenterology. 1999 Jul;117(1):167-72 - PubMed
  2. Cell Metab. 2013 May 7;17(5):657-69 - PubMed
  3. Dig Dis Sci. 1991 Feb;36(2):216-20 - PubMed
  4. Gastroenterology. 2015 Apr;148(4):751-61.e8 - PubMed
  5. Semin Immunopathol. 2014 Sep;36(5):553-68 - PubMed
  6. Am J Physiol Gastrointest Liver Physiol. 2013 Sep 15;305(6):G427-38 - PubMed
  7. Liver Int. 2017 Jan;37 Suppl 1:123-129 - PubMed
  8. Saudi J Gastroenterol. 2016 Mar-Apr;22(2):122-6 - PubMed
  9. Gut. 2002 Mar;50(3):436-9 - PubMed
  10. J Gastroenterol. 2009;44(6):630-4 - PubMed
  11. Hepatology. 2007 Mar;45(3):666-74 - PubMed
  12. Gastroenterology. 2005 Feb;128(2):297-303 - PubMed
  13. Gastroenterology. 1992 Feb;102(2):544-9 - PubMed
  14. J Clin Gastroenterol. 2011 Aug;45(7):e66-71 - PubMed
  15. Lancet. 2003 Jul 5;362(9377):53-61 - PubMed
  16. Hepatology. 2005 May;41(5):1106-12 - PubMed
  17. QJM. 2002 Aug;95(8):547-52 - PubMed
  18. Nat Rev Endocrinol. 2014 Aug;10(8):488-98 - PubMed
  19. J Hepatol. 2012 Sep;57(3):637-41 - PubMed
  20. Internist (Berl). 2017 Feb;58(2):202-204 - PubMed
  21. J Hepatol. 2010 Aug;53(2):307-12 - PubMed
  22. Hepatology. 2005 Jan;41(1):168-76 - PubMed
  23. Hepatology. 2008 Sep;48(3):871-7 - PubMed
  24. Lancet. 2015 Oct 17;386(10003):1565-75 - PubMed
  25. Biochem Biophys Res Commun. 1992 Oct 30;188(2):942-8 - PubMed
  26. Gastroenterology. 2016 May;150(5):1147-1159.e5 - PubMed
  27. Gastroenterology. 2015 Nov;149(6):1627-9 - PubMed
  28. Liver Int. 2017 May;37(5):743-747 - PubMed
  29. J Hepatol. 2008 Jan;48(1):116-24 - PubMed
  30. Hepatology. 2006 Jul;44(1):280-1 - PubMed
  31. Gut. 2016 Feb;65(2):321-9 - PubMed
  32. Hepatology. 2006 Nov;44(5):1317-23 - PubMed
  33. Anaesthesia. 1989 Oct;44(10):863 - PubMed
  34. Hepatology. 2009 Jul;50(1):291-308 - PubMed
  35. Am J Gastroenterol. 2006 Jul;101(7):1529-38 - PubMed
  36. Gastroenterology. 1966 Mar;50(3):323-32 - PubMed
  37. J Hepatol. 2017 Jul;67(1):145-172 - PubMed
  38. J Hepatol. 2001 Jul;35(1):134-46 - PubMed
  39. J Pharmacol Exp Ther. 2005 Oct;315 (1):58-68 - PubMed
  40. Hepatology. 2012 Aug;56(2):687-97 - PubMed
  41. Clin Gastroenterol Hepatol. 2008 Sep;6(9):1041-8 - PubMed
  42. J Pharmacol Exp Ther. 2005 Aug;314(2):584-95 - PubMed
  43. Ann Hepatol. 2016 Jul-Aug;15(4):604-9 - PubMed
  44. J Lipid Res. 2014 Aug;55(8):1553-95 - PubMed
  45. Drug Des Devel Ther. 2015 May 25;9:2757-66 - PubMed
  46. J Hepatol. 2011 Dec;55(6):1361-7 - PubMed
  47. Hepatology. 2016 Mar;63(3):930-50 - PubMed
  48. Cell. 2000 Sep 15;102(6):731-44 - PubMed
  49. Br J Clin Pharmacol. 2012 May;73(5):826-7 - PubMed
  50. Am J Hosp Palliat Care. 2013 Mar;30(2):192-6 - PubMed
  51. Annu Rev Biochem. 2003;72:137-74 - PubMed
  52. Gastroenterology. 1988 Feb;94(2):488-93 - PubMed
  53. Can J Gastroenterol. 2008 May;22(5):505-7 - PubMed
  54. Hepatology. 2006 May;43(5):1170-1 - PubMed
  55. Hepatology. 1997 Jan;25(1):12-7 - PubMed
  56. Gastroenterology. 2015 Dec;149(7):1804-1812.e4 - PubMed
  57. Clin Liver Dis. 2003 Nov;7(4):779-94 - PubMed
  58. Hepatology. 1995 Sep;22(3):759-66 - PubMed
  59. Gastroenterology. 2013 Mar;144(3):560-569.e7; quiz e13-4 - PubMed
  60. Hepatology. 1994 May;19(5):1149-56 - PubMed
  61. Gut. 1972 Dec;13(12):976-81 - PubMed
  62. BMJ. 1988 Dec 10;297(6662):1501-4 - PubMed
  63. J Immunol. 1996 Feb 15;156(4):1601-8 - PubMed
  64. J Biol Chem. 2001 Dec 14;276(50):47371-8 - PubMed
  65. Am J Gastroenterol. 2010 Oct;105(10):2186-94 - PubMed
  66. Nat Clin Pract Gastroenterol Hepatol. 2006 Jun;3(6):318-28 - PubMed
  67. J Biol Chem. 2001 Aug 3;276(31):28857-65 - PubMed
  68. N Engl J Med. 1991 May 30;324(22):1548-54 - PubMed
  69. Eur J Clin Invest. 2000 Mar;30(3):203-9 - PubMed
  70. Mol Cell Biol. 2012 May;32(10):1944-54 - PubMed
  71. Aliment Pharmacol Ther. 2012 Mar;35(6):696-704 - PubMed
  72. Dig Dis Sci. 2016 Oct;61(10 ):3037-3044 - PubMed
  73. J Hepatol. 2002 Dec;37(6):717-22 - PubMed
  74. Gastroenterology. 2006 Mar;130(3):715-20 - PubMed
  75. Lancet. 2017 Mar 18;389(10074):1114-1123 - PubMed
  76. Am J Gastroenterol. 2003 Dec;98(12):2736-41 - PubMed
  77. Liver. 1999 Apr;19(2):115-21 - PubMed
  78. Lancet. 1989 Mar 18;1(8638):574-6 - PubMed
  79. Semin Liver Dis. 2007 May;27(2):161-72 - PubMed
  80. Liver Int. 2006 Oct;26(8):943-8 - PubMed
  81. Eur J Clin Invest. 2000 Feb;30(2):135-9 - PubMed
  82. Annu Rev Pathol. 2013 Jan 24;8:303-30 - PubMed
  83. Gastroenterology. 1994 May;106(5):1284-90 - PubMed
  84. Gastroenterology. 2009 Apr;136(4):1281-7 - PubMed
  85. Gastroenterology. 2003 Sep;125(3):868-81 - PubMed
  86. Aliment Pharmacol Ther. 2016 Jan;43(2):294-302 - PubMed
  87. Am J Med. 2017 Jun;130(6):744.e1-744.e7 - PubMed
  88. Postgrad Med J. 2008 Jan;84(987):23-33 - PubMed

Publication Types

Grant support