Display options
Cite
Purohit T, Cappell MS. Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy. World J Hepatol. 2015;7(7):926-41doi: 10.4254/wjh.v7.i7.926.
Purohit, T., & Cappell, M. S. (2015). Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy. World journal of hepatology, 7(7), 926-41. https://doi.org/10.4254/wjh.v7.i7.926
Purohit, Treta, and Cappell, Mitchell S. "Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy." World journal of hepatology vol. 7,7 (2015): 926-41. doi: https://doi.org/10.4254/wjh.v7.i7.926
Purohit T, Cappell MS. Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy. World J Hepatol. 2015 May 08;7(7):926-41. doi: 10.4254/wjh.v7.i7.926. PMID: 25954476; PMCID: PMC4419097.
Copy Download .nbib Format: NLM
Share it on

World J Hepatol. 2015 May 08;7(7):926-41. doi: 10.4254/wjh.v7.i7.926.

Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy.

World journal of hepatology

Treta Purohit, Mitchell S Cappell

Affiliations

  1. Treta Purohit, Mitchell S Cappell, Division of Gastroenterology and Hepatology, William Beaumont Hospital, Royal Oak, MI 48073, United States.

PMID: 25954476 PMCID: PMC4419097 DOI: 10.4254/wjh.v7.i7.926

Abstract

Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren's syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva substitutes, cholinergic agents, and scrupulous oral and dental care. Complications of cirrhosis from advanced PBC include esophageal varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatoma formation.

Keywords: Cholestatic liver disease; Cirrhosis; Liver transplantation; Primary biliary cirrhosis; Ursodeoxycholic acid

References

  1. Hepatology. 2012 Feb;55(2):512-21 - PubMed
  2. J Hepatol. 1993 Feb;17(2):227-35 - PubMed
  3. Gastroenterology. 1999 Sep;117(3):640-4 - PubMed
  4. Clin Liver Dis. 2008 May;12(2):323-31; viii-ix - PubMed
  5. Hepatology. 1998 Jul;28(1):33-8 - PubMed
  6. J Gastroenterol Hepatol. 2012 Jul;27(7):1150-8 - PubMed
  7. Hepatology. 2011 Mar;53(3):1020-2 - PubMed
  8. Gastroenterology. 2000 Feb;118(2):431-2 - PubMed
  9. Open Cardiovasc Med J. 2010 Apr 28;4:120-6 - PubMed
  10. Clin Liver Dis. 2008 May;12(2):407-24; x - PubMed
  11. Lancet. 2005 Jul 23-29;366(9482):321-31 - PubMed
  12. MedGenMed. 2006 May 03;8(2):30 - PubMed
  13. Scand J Gastroenterol Suppl. 1992;192:43-9 - PubMed
  14. Lancet. 2003 Nov 29;362(9398):1819-27 - PubMed
  15. Lancet. 1995 Jul 29;346(8970):270-4 - PubMed
  16. Can J Gastroenterol. 2013 Jul;27(7):417-23 - PubMed
  17. N Engl J Med. 1996 Nov 21;335(21):1570-80 - PubMed
  18. Radiographics. 2000 Jul-Aug;20(4):959-75; quiz 1108-9, 1112 - PubMed
  19. Clin Gastroenterol Hepatol. 2007 Jul;5(7):803-8 - PubMed
  20. N Engl J Med. 2001 Aug 30;345(9):669-81 - PubMed
  21. Semin Liver Dis. 1997 Feb;17(1):23-33 - PubMed
  22. Liver Transpl. 2007 Sep;13(9):1236-45 - PubMed
  23. Gastroenterology. 1999 Oct;117(4):918-25 - PubMed
  24. Gastroenterology. 2015 Apr;148(4):751-61.e8 - PubMed
  25. Br J Ophthalmol. 2005 Oct;89(10):1363-7 - PubMed
  26. Gut. 2010 Apr;59(4):508-12 - PubMed
  27. Clin Rev Allergy Immunol. 2015 Jun;48(2-3):192-7 - PubMed
  28. Eur J Gastroenterol Hepatol. 2010 Dec;22(12):1495-502 - PubMed
  29. Medicine (Baltimore). 1950 Dec;29(4):299-364 - PubMed
  30. Clin Rev Allergy Immunol. 2015 Jun;48(2-3):236-42 - PubMed
  31. Atherosclerosis. 2007 Oct;194(2):293-9 - PubMed
  32. Am J Gastroenterol. 2002 May;97(5):1191-7 - PubMed
  33. Prz Gastroenterol. 2014;9(2):82-7 - PubMed
  34. Ann Intern Med. 1980 Jul;93(1):59-60 - PubMed
  35. Hepatology. 2000 Nov;32(5):897-900 - PubMed
  36. Clin Gastroenterol Hepatol. 2014 May;12(5):863-9 - PubMed
  37. Gut. 2002 Mar;50(3):436-9 - PubMed
  38. Hepatology. 2005 Nov;42(5):1194-202 - PubMed
  39. World J Gastroenterol. 2014 Apr 7;20(13):3597-608 - PubMed
  40. Gastroenterology. 1993 Feb;104(2):519-26 - PubMed
  41. Hepatology. 2007 Mar;45(3):666-74 - PubMed
  42. Gastroenterology. 1999 Aug;117(2):400-7 - PubMed
  43. Pain. 1988 May;33(2):149-60 - PubMed
  44. J Gastroenterol Hepatol. 2012 Jul;27(7):1159-66 - PubMed
  45. Hepatology. 2000 Feb;31(2):318-23 - PubMed
  46. J Bone Miner Metab. 2008;26(4):379-84 - PubMed
  47. JAMA. 2001 May 2;285(17):2196-7 - PubMed
  48. Hepatogastroenterology. 2013 May;60(123):568-76 - PubMed
  49. Am J Cardiol. 2004 Oct 1;94(7):935-8 - PubMed
  50. Dig Dis. 2014;32(5):615-25 - PubMed
  51. Nat Clin Pract Gastroenterol Hepatol. 2007 Apr;4(4):200-1 - PubMed
  52. Hepatology. 2013 Apr;57(4):1651-3 - PubMed
  53. Ann Transplant. 2014 Sep 29;19:488-93 - PubMed
  54. QJM. 2002 Aug;95(8):547-52 - PubMed
  55. Clin Res Hepatol Gastroenterol. 2012 Sep;36 Suppl 1:S3-12 - PubMed
  56. Am J Gastroenterol. 2010 Feb;105(2):345-53 - PubMed
  57. Hepatology. 2007 Mar;45(3):659-65 - PubMed
  58. Clin Infect Dis. 1994 Jan;18 Suppl 1:S79-83 - PubMed
  59. Eur J Gastroenterol Hepatol. 2001 Nov;13(11):1393-4 - PubMed
  60. J Pharm Sci. 2005 Jun;94(6):1169-86 - PubMed
  61. Drugs. 1995 Nov;50(5):854-72 - PubMed
  62. Dig Dis Sci. 2009 Oct;54(10):2242-6 - PubMed
  63. Semin Liver Dis. 2014 Aug;34(3):318-28 - PubMed
  64. Clin Liver Dis. 2012 May;16(2):199-229 - PubMed
  65. J Hepatol. 2010 Aug;53(2):307-12 - PubMed
  66. Curr Opin Gastroenterol. 2011 May;27(3):285-8 - PubMed
  67. J Hepatol. 1999 Mar;30(3):408-12 - PubMed
  68. Gastroenterol Res Pract. 2013;2013:490731 - PubMed
  69. Hepatology. 2008 Sep;48(3):871-7 - PubMed
  70. J Gastroenterol Hepatol. 2004 Jun;19(6):699-706 - PubMed
  71. Postgrad Med J. 2008 Dec;84(998):662-70 - PubMed
  72. Gut. 2005 Mar;54(3):407-10 - PubMed
  73. Am J Surg Pathol. 2006 Nov;30(11):1454-61 - PubMed
  74. Aliment Pharmacol Ther. 2014 Jul;40(2):123-32 - PubMed
  75. Gastroenterology. 1997 Sep;113(3):884-90 - PubMed
  76. J Hepatol. 2002 Apr;36(4):454-8 - PubMed
  77. BMC Gastroenterol. 2012 Aug 16;12:110 - PubMed
  78. J Hepatol. 2009 Aug;51(2):237-67 - PubMed
  79. Gastroenterology. 1995 May;108(5):1470-8 - PubMed
  80. Aliment Pharmacol Ther. 2003 Nov 15;18(10):963-72 - PubMed
  81. Liver Int. 2008 Feb;28(2):233-9 - PubMed
  82. Hepatology. 2006 Jul;44(1):280-1 - PubMed
  83. Hepatology. 2010 Aug;52(2):562-70 - PubMed
  84. Autoimmunity. 2013 Nov;46(7):471-9 - PubMed
  85. Hepatology. 2002 Sep;36(3):525-31 - PubMed
  86. J Hepatol. 2009 Jun;50(6):1202-9 - PubMed
  87. Gastroenterology. 2004 Aug;127(2):485-92 - PubMed
  88. Hepatology. 2009 Jul;50(1):291-308 - PubMed
  89. Cochrane Database Syst Rev. 2012 Dec 12;12:CD000551 - PubMed
  90. Hepatology. 2001 Jan;33(1):22-7 - PubMed
  91. Gastroenterology. 1966 Mar;50(3):323-32 - PubMed
  92. Gut. 2006 Dec;55(12 ):1795-800 - PubMed
  93. Clin Gastroenterol Hepatol. 2014 Aug;12(8):1398-405 - PubMed
  94. Liver Transpl. 2011 Oct;17 Suppl 2:S44-57 - PubMed
  95. Psychoneuroendocrinology. 2004 Apr;29(3):339-54 - PubMed
  96. Gastroenterology. 1992 Jun;102(6):2077-80 - PubMed
  97. J Hepatol. 2010 Jul;53(1):162-9 - PubMed
  98. N Engl J Med. 1982 Jan 7;306(1):1-4 - PubMed
  99. Am J Gastroenterol. 2009 Jun;104(6):1420-5 - PubMed
  100. Liver Transpl. 2003 Jul;9(7):733-6 - PubMed
  101. Liver Transpl. 2000 Nov;6(6):749-52 - PubMed
  102. Clin Transpl. 2012;:41-65 - PubMed
  103. Am J Gastroenterol. 2004 Jun;99(6):1105-10 - PubMed
  104. Hepatology. 2005 Apr;41(4):747-52 - PubMed
  105. Gut. 2005 Nov;54(11):1622-9 - PubMed
  106. Dig Liver Dis. 2003 Feb;35(2):128-9 - PubMed
  107. Hepatology. 2001 Aug;34(2):243-8 - PubMed
  108. Liver Int. 2004 Jun;24(3):187-93 - PubMed
  109. J Autoimmun. 2010 Feb;34(1):55-8 - PubMed
  110. Liver Int. 2015 Feb;35(2):636-41 - PubMed
  111. Hepatology. 2005 Apr;41(4):690-5 - PubMed
  112. Gut. 2002 Aug;51(2):265-9 - PubMed
  113. Proc R Soc Med. 1967 Dec;60(12):1257-60 - PubMed
  114. Dig Dis. 2014;32(4):438-45 - PubMed
  115. Semin Liver Dis. 2005 Aug;25(3):298-310 - PubMed
  116. J Clin Gastroenterol. 2005 Feb;39(2):168-71 - PubMed
  117. Clin Rev Allergy Immunol. 2012 Jun;42(3):288-97 - PubMed
  118. Lancet. 1965 Apr 17;1(7390):827-31 - PubMed
  119. Gut. 2004 Apr;53(4):587-92 - PubMed
  120. Clin Liver Dis. 2003 Nov;7(4):741-58 - PubMed
  121. Arch Med Res. 2014 Apr;45(3):270-9 - PubMed
  122. Occup Med (Lond). 2010 Mar;60(2):159 - PubMed
  123. Gut. 1985 Feb;26(2):114-9 - PubMed
  124. Hepatology. 2000 May;31(5):1055-60 - PubMed
  125. Transplantation. 2002 Jan 27;73(2):224-7 - PubMed
  126. Hepatology. 1989 Jul;10(1):1-7 - PubMed
  127. Clin Gastroenterol Hepatol. 2008 Sep;6(9):1041-8 - PubMed
  128. Aliment Pharmacol Ther. 2006 Dec;24(11-12):1535-44 - PubMed
  129. Hepatology. 2003 Jul;38(1):196-202 - PubMed
  130. Hepatology. 1998 Aug;28(2):360-5 - PubMed
  131. Hepatology. 2013 May;57(5):1931-41 - PubMed
  132. Drugs. 1984 Dec;28(6):485-518 - PubMed
  133. Autoimmun Rev. 2014 Sep;13(9):931-5 - PubMed
  134. J Hepatol. 1989 Sep;9(2):149-58 - PubMed
  135. Gastroenterology. 1969 Sep;57(3):253-5 - PubMed
  136. J Hepatol. 1997 Jul;27(1):143-9 - PubMed
  137. J Med Chem. 2002 Aug 15;45(17 ):3569-72 - PubMed
  138. Gastroenterology. 1988 Feb;94(2):488-93 - PubMed
  139. Am J Gastroenterol. 2013 Jun;108(6):933-41 - PubMed
  140. Hepatology. 2007 Oct;46(4):1131-7 - PubMed
  141. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2527-31 - PubMed
  142. J Hepatol. 2006 Feb;44(2):400-6 - PubMed
  143. Hepatology. 2008 May;47(5):1764-72 - PubMed
  144. Gut. 1998 Nov;43(5):705-10 - PubMed
  145. Ann Hepatol. 2010 Apr-Jun;9(2):181-5 - PubMed
  146. Hepatology. 2005 Nov;42(5):1184-93 - PubMed
  147. Hepatology. 1997 Nov;26(5):1138-42 - PubMed
  148. Hepatology. 2001 Jan;33(1):16-21 - PubMed
  149. Clin Obstet Gynecol. 2013 Dec;56(4):703-10 - PubMed
  150. N Engl J Med. 2010 Mar 25;362(12):1071-81 - PubMed
  151. Gastroenterology. 1986 Dec;91(6):1327-34 - PubMed
  152. Liver Int. 2014 Feb;34(2):197-203 - PubMed
  153. Hepatology. 2007 Sep;46(3):776-84 - PubMed
  154. Curr Infect Dis Rep. 2013 Feb;15(1):14-24 - PubMed
  155. World J Gastroenterol. 2014 Mar 14;20(10):2606-12 - PubMed
  156. Semin Liver Dis. 2014 Aug;34(3):265-72 - PubMed
  157. J Hepatol. 1995 Dec;23(6):674-80 - PubMed
  158. Liver Transpl. 2003 Apr;9(4):437-43 - PubMed
  159. Ann Transplant. 2008;13(3):35-42 - PubMed
  160. Autoimmun Rev. 2014 Apr-May;13(4-5):441-4 - PubMed
  161. Nat Clin Pract Gastroenterol Hepatol. 2006 Jun;3(6):318-28 - PubMed
  162. Hepatology. 2008 Oct;48(4):1149-56 - PubMed
  163. Am J Gastroenterol. 2006 Sep;101(9):2044-50 - PubMed
  164. J Clin Gastroenterol. 2010 May-Jun;44(5):371-3 - PubMed
  165. Liver Transpl. 2010 Jan;16(1):64-73 - PubMed
  166. Hepatology. 1999 May;29(5):1396-8 - PubMed
  167. Liver Int. 2006 Sep;26(7):840-5 - PubMed
  168. J Hepatol. 1994 Oct;21(4):496-9 - PubMed
  169. Liver Transpl. 2007 Jun;13(6):938-9 - PubMed
  170. Aliment Pharmacol Ther. 2012 Sep;36(6):517-33 - PubMed
  171. Clin Gastroenterol Hepatol. 2007 Nov;5(11):1313-5 - PubMed
  172. Curr Vasc Pharmacol. 2014 Jan;12(1):125-35 - PubMed
  173. Clin Chim Acta. 1980 Dec 22;108(3):457-63 - PubMed
  174. Eur J Clin Pharmacol. 1985;28(4):475-7 - PubMed
  175. J Gastroenterol. 2005 May;40(5):546-7 - PubMed
  176. Am J Gastroenterol. 2007 Jun;102(6):1244-50 - PubMed
  177. Gut. 2012 Feb;61(2):297-310 - PubMed
  178. Semin Liver Dis. 2014 Aug;34(3):352-60 - PubMed
  179. J Gastroenterol Hepatol. 2013 Aug;28(8):1397-402 - PubMed
  180. Eur J Intern Med. 2009 Jul;20(4):398-402 - PubMed
  181. Neurogastroenterol Motil. 2008 Jun;20(6):671-9 - PubMed
  182. Liver Int. 2005 Feb;25(1):117-21 - PubMed
  183. Gastroenterology. 2006 Mar;130(3):715-20 - PubMed
  184. Hepatology. 1989 Oct;10(4):403-7 - PubMed
  185. Virchows Arch A Pathol Anat Histol. 1978 Aug 22;379(2):103-12 - PubMed
  186. Nat Rev Gastroenterol Hepatol. 2010 Jun;7(6):313-9 - PubMed
  187. Liver Transpl. 2007 Jan;13(1):80-90 - PubMed
  188. Best Pract Res Clin Gastroenterol. 2010 Oct;24(5):647-54 - PubMed
  189. Gastroenterology. 2005 Aug;129(2):476-85 - PubMed
  190. Am J Gastroenterol. 2003 Dec;98(12):2736-41 - PubMed
  191. Liver. 1999 Apr;19(2):115-21 - PubMed
  192. Gut. 1995 Jun;36(6):927-30 - PubMed
  193. Curr Opin Gastroenterol. 2014 May;30(3):279-86 - PubMed
  194. Liver Transpl. 2005 Oct;11(10):1252-7 - PubMed
  195. Expert Opin Pharmacother. 2010 Feb;11(3):387-92 - PubMed
  196. Transplant Proc. 2005 Apr;37(3):1480-1 - PubMed
  197. Semin Liver Dis. 2014 Aug;34(3):329-33 - PubMed
  198. J Hepatol. 2006 Dec;45(6):887-91 - PubMed
  199. Hepatology. 1997 May;25(5):1090-5 - PubMed
  200. Clin Gastroenterol Hepatol. 2007 Feb;5(2):259-64 - PubMed
  201. Semin Liver Dis. 2014 Aug;34(3):341-51 - PubMed
  202. Annu Rev Pathol. 2013 Jan 24;8:303-30 - PubMed
  203. Hepatology. 1998 Aug;28(2):296-301 - PubMed
  204. Aliment Pharmacol Ther. 2010 Mar;31(5):537-47 - PubMed
  205. World J Gastroenterol. 2012 Sep 28;18(36):4978-84 - PubMed
  206. J Am Acad Dermatol. 1986 Feb;14(2 Pt 1):161-77 - PubMed
  207. Gut. 1971 Oct;12(10):830-4 - PubMed
  208. Gastroenterol Clin North Am. 2008 Jun;37(2):479-84, viii - PubMed
  209. Clin Res Hepatol Gastroenterol. 2011 Jun;35(6-7):446-54 - PubMed
  210. Hepatology. 1996 Nov;24(5):1098-103 - PubMed
  211. Liver Transpl. 2004 Apr;10(4):488-91 - PubMed
  212. Liver. 2002;22 Suppl 2:72-5 - PubMed
  213. Gastroenterology. 1985 Nov;89(5):1084-91 - PubMed
  214. Clin Rev Allergy Immunol. 2007 Jun;32(3):284-91 - PubMed
  215. Liver Transpl. 2000 Jul;6(4):489-94 - PubMed
  216. Arch Dermatol. 2012 Jul;148(7):794-6 - PubMed
  217. Clin Gastroenterol Hepatol. 2008 Feb;6(2):228-33 - PubMed
  218. Aliment Pharmacol Ther. 2011 Jan;33(2):235-42 - PubMed

Publication Types