Primary Biliary Cirrhosis Clinical Presentation

  • Author: Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP; Chief Editor: Julian Katz, MD   more...
 
Updated: Jan 4, 2012
 

History

Of patients with primary biliary cirrhosis, 25% are incidentally diagnosed during a routine blood evaluation.

  • Fatigue (65%)
    • Fatigue is the first reported symptom. It can cause disability in some patients and has been associated with depression and obsessive-compulsive behavior. The etiology is unknown; however, a sleep abnormality, particularly excessive daytime somnolence, has been identified in a significant proportion of patients and has been associated with the degree of fatigue.
    • No correlation exists between this symptom and the stage of the liver disease, the height of the levels of liver enzymes, the Mayo model score, or the duration of therapy.
    • The etiology of fatigue is unclear; although some evidence suggests that abnormalities of the hypothalamic-pituitary-adrenal axis, decreased release of serotonin, and increased production of proinflammatory cytokines (ie, interleukin-1 [IL-1], interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α] ) may be responsible.[6]
  • Pruritus (55%)
    • According to estimates, 10% of patients experience severe pruritus.
    • The cause of this symptom is not known.
    • Pruritus appears unrelated to the deposition of bile acids in the skin.
    • Increased opioidergic tone (ie, increased production of endogenous opioid peptides, up-regulation of endogenous opioid receptors) appears to be the major mechanism. The height of the bilirubin level is proportionally related to the production of these peptides.
  • Right upper quadrant discomfort occurs in 8-17% of patients.
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Physical

Physical examination findings depend on the stage of the disease. In the early stages, examination findings are normal. As the disease advances, excoriations of the skin, xanthelasmata, or findings of cirrhosis may be present.

  • Hepatomegaly (25%)
  • Hyperpigmentation (25%)
  • Splenomegaly (15%)
  • Jaundice (10%)
  • Xanthelasmata (10%) - In late stages of the disease
  • Sicca syndrome (50-75%) - Xerophthalmia (ie, dry eyes), xerostomia (ie, dry mouth)
  • Kayser-Fleischer rings (extremely rare)
  • Stigmata of advanced liver disease (ie, cirrhosis), such as spider nevi, palmar erythema, ascites, temporal and proximal muscle wasting, and peripheral edema
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Causes

Primary biliary cirrhosis is a disease of unknown etiology, but various factors have been implicated as the causes of this illness.

  • Genetic factors: First-degree relatives have a 570- to 1000-fold increased chance of developing primary biliary cirrhosis. The presence of an inherited abnormality of immune regulation has been proposed.
  • Infection with organisms of the family Enterobacteriaceae: Cross-reactivity between antigens on the bacterial wall and the mitochondria has been postulated. Patients with primary biliary cirrhosis present with an increased incidence of gram-negative urinary tract infections.
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Contributor Information and Disclosures
Author

Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP  Chair of Hepatology, Medical Director of Liver Transplantation, Liver Unit, Florida Hospital; Associate Professor of Medicine, University of Central Florida College of Medicine

Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Liver Foundation, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Transplantation, International Liver Transplantation Society, and Transplantation Society

Disclosure: Gilead Sciences Honoraria Speaking and teaching; Schering-Plough Honoraria Speaking and teaching; Roche Honoraria Speaking and teaching

Coauthor(s)

K Rajender Reddy, MD, FACP, FACG  Professor of Medicine, Director of Hepatology, Medical Director of Liver Transplantation, Hospital of the University of Pennsylvania

K Rajender Reddy, MD, FACP, FACG is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and Florida Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

George Y Wu, MD, PhD  Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine

George Y Wu, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, American Society for Clinical Investigation, and Association of American Physicians

Disclosure: Springer Consulting fee Consulting; Gilead Consulting fee Review panel membership; Gilead Honoraria Speaking and teaching; Bristol-Myers Squibb Honoraria Speaking and teaching; Springer Royalty Review panel membership

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

James L Achord, MD  Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine

James L Achord, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Mississippi State Medical Association, New York Academy of Sciences, Sigma Xi, and Southern Medical Association

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

References

  1. Ahrens EH Jr, Payne MA, Kunkel HG, et al. Primary biliary cirrhosis. 1950. Medicine (Baltimore). Sep 1994;73(5):264-78; discussion 278-80. [Medline].

  2. Solis Herruzo JA, Solis Munoz P, Munoz Yague T. The pathogenesis of primary biliary cirrhosis. Rev Esp Enferm Dig. Jun 2009;101(6):413-23. [Medline].

  3. McNally RJ, Ducker S, James OF. Are transient environmental agents involved in the cause of primary biliary cirrhosis? Evidence from space-time clustering analysis. Hepatology. Jun 24 2009;[Medline].

  4. Selmi C, Gershwin ME. The role of environmental factors in primary biliary cirrhosis. Trends Immunol. Aug 2009;30(8):415-20. [Medline].

  5. Mendes FD, Kim WR, Pedersen R, et al. Mortality attributable to cholestatic liver disease in the United States. Hepatology. Apr 2008;47(4):1241-7. [Medline].

  6. Niro GA, Poli F, Andriulli A, Bianchi I, Bernuzzi F, Caliari L, et al. TNF-alpha polymorphisms in primary biliary cirrhosis: a northern and southern Italian experience. Ann N Y Acad Sci. Sep 2009;1173:557-63. [Medline].

  7. Drebber U, Mueller JJ, Klein E, Kasper HU, Schulze F, Schardt K, et al. Liver biopsy in primary biliary cirrhosis: clinicopathological data and stage. Pathol Int. Aug 2009;59(8):546-54. [Medline].

  8. Scheuer P. Primary biliary cirrhosis. Proc R Soc Med. Dec 1967;60(12):1257-60. [Medline]. [Full Text].

  9. Charatcharoenwitthaya P, Pimentel S, Talwalkar JA, et al. Long-term survival and impact of ursodeoxycholic acid treatment for recurrent primary biliary cirrhosis after liver transplantation. Liver Transpl. Sep 2007;13(9):1236-45. [Medline].

  10. Tsuda M, Moritoki Y, Lian ZX, Zhang W, Yoshida K, Wakabayashi K, et al. Biochemical and immunologic effects of rituximab in primary biliary cirrhosis patients with an incomplete response to ursodeoxycholic acid. Hepatology. Oct 17 2011;[Medline].

  11. Rudic JS, Giljaca V, Krstic MN, Bjelakovic G, Gluud C. Bisphosphonates for osteoporosis in primary biliary cirrhosis. Cochrane Database Syst Rev. Dec 7 2011;12:CD009144. [Medline].

  12. Bjornsson E, Kalaitzakis E, Neuhauser M, et al. Fatigue measurements in patients with primary biliary cirrhosis and the risk of mortality during follow-up. Liver Int. Nov 17 2009;[Medline].

  13. Balasubramaniam K, Grambsch PM, Wiesner RH, et al. Diminished survival in asymptomatic primary biliary cirrhosis. A prospective study. Gastroenterology. Jun 1990;98(6):1567-71. [Medline].

  14. Ballardini G, Mirakian R, Bianchi FB, et al. Aberrant expression of HLA-DR antigens on bileduct epithelium in primary biliary cirrhosis: relevance to pathogenesis. Lancet. Nov 3 1984;2(8410):1009-13. [Medline].

  15. Burroughs AK, Rosenstein IJ, Epstein O, et al. Bacteriuria and primary biliary cirrhosis. Gut. Feb 1984;25(2):133-7. [Medline].

  16. Bush A, Mitchison H, Walt R, et al. Primary biliary cirrhosis and ulcerative colitis. Gastroenterology. Jun 1987;92(6):2009-13. [Medline].

  17. Calmus Y, Gane P, Rouger P, et al. Hepatic expression of class I and class II major histocompatibility complex molecules in primary biliary cirrhosis: effect of ursodeoxycholic acid. Hepatology. Jan 1990;11(1):12-5. [Medline].

  18. Christensen E, Crowe J, Doniach D, et al. Clinical pattern and course of disease in primary biliary cirrhosis based on an analysis of 236 patients. Gastroenterology. Feb 1980;78(2):236-46. [Medline].

  19. Culp KS, Fleming CR, Duffy J, et al. Autoimmune associations in primary biliary cirrhosis. Mayo Clin Proc. Jun 1982;57(6):365-70. [Medline].

  20. Dickson ER, Grambsch PM, Fleming TR, et al. Prognosis in primary biliary cirrhosis: model for decision making. Hepatology. Jul 1989;10(1):1-7. [Medline].

  21. Elta GH, Sepersky RA, Goldberg MJ, et al. Increased incidence of hypothyroidism in primary biliary cirrhosis. Dig Dis Sci. Nov 1983;28(11):971-5. [Medline].

  22. Gershwin ME, Selmi C, Worman HJ, Gold EB, Watnik M, Utts J, et al. Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients. Hepatology. Nov 2005;42(5):1194-202. [Medline].

  23. Hoffmann RM, Pape GR, Spengler U, et al. Clonal analysis of liver-derived T cells of patients with primary biliary cirrhosis. Clin Exp Immunol. May 1989;76(2):210-5. [Medline].

  24. Janes CH, Dickson ER, Okazaki R, et al. Role of hyperbilirubinemia in the impairment of osteoblast proliferation associated with cholestatic jaundice. J Clin Invest. Jun 1995;95(6):2581-6. [Medline].

  25. Jones DE, Metcalf JV, Collier JD, et al. Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes. Hepatology. Nov 1997;26(5):1138-42. [Medline].

  26. Kaplan MM, Elta GH, Furie B, et al. Fat-soluble vitamin nutriture in primary biliary cirrhosis. Gastroenterology. Sep 1988;95(3):787-92. [Medline].

  27. Kim WR, Lindor KD, Locke GR 3rd, et al. Epidemiology and natural history of primary biliary cirrhosis in a US community. Gastroenterology. Dec 2000;119(6):1631-6. [Medline].

  28. Klein R, Huizenga JR, Gips CH, et al. Antimitochondrial antibody profiles in patients with primary biliary cirrhosis before orthotopic liver transplantation and titres of antimitochondrial antibody-subtypes after transplantation. J Hepatol. Feb 1994;20(2):181-9. [Medline].

  29. Lacerda MA, Ludwig J, Dickson ER, et al. Antimitochondrial antibody-negative primary biliary cirrhosis. Am J Gastroenterol. Feb 1995;90(2):247-9. [Medline].

  30. Liermann Garcia RF, Evangelista Garcia C, et al. Transplantation for primary biliary cirrhosis: retrospective analysis of 400 patients in a single center. Hepatology. Jan 2001;33(1):22-7. [Medline].

  31. Lindor K, Dickson R. Primary biliary cirrhosis. In: Schiff's Diseases of the Liver. Vol 1. 8th ed. Lippincott-Raven: 1999:679-92.

  32. Mahl TC, Shockcor W, Boyer JL. Primary biliary cirrhosis: survival of a large cohort of symptomatic and asymptomatic patients followed for 24 years. J Hepatol. Jun 1994;20(6):707-13. [Medline].

  33. Mang FW, Michieletti P, O'Rourke K, et al. Primary biliary cirrhosis, sicca complex, and dysphagia. Dysphagia. Summer 1997;12(3):167-70. [Medline].

  34. Marx WJ, O'Connell DJ. Arthritis of primary biliary cirrhosis. Arch Intern Med. Feb 1979;139(2):213-6. [Medline].

  35. Nakanuma Y, Tsuneyama K, Kono N, et al. Biliary epithelial expression of pyruvate dehydrogenase complex in primary biliary cirrhosis: an immunohistochemical and immunoelectron microscopic study. Hum Pathol. Jan 1995;26(1):92-8. [Medline].

  36. Newton JL, Gibson GJ, Tomlinson M, Wilton K, Jones D. Fatigue in primary biliary cirrhosis is associated with excessive daytime somnolence. Hepatology. Jul 2006;44(1):91-8. [Medline].

  37. Pares A, Rimola A, Bruguera M, et al. Renal tubular acidosis in primary biliary cirrhosis. Gastroenterology. Apr 1981;80(4):681-6. [Medline].

  38. Parikh-Patel A, Gold E, Mackay IR, et al. The geoepidemiology of primary biliary cirrhosis: contrasts and comparisons with the spectrum of autoimmune diseases. Clin Immunol. May 1999;91(2):206-18. [Medline].

  39. Parés A, Caballería L, Rodés J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic Acid. Gastroenterology. Mar 2006;130(3):715-20. [Medline].

  40. Reynolds TB, Denison EK, Frankl HD, Lieberman FL, Peters RL. Primary biliary cirrhosis with scleroderma, Raynaud's phenomenon and telangiectasia. New syndrome. Am J Med. Mar 1971;50(3):302-12. [Medline].

  41. Ricci P, Therneau TM, Malinchoc M, et al. A prognostic model for the outcome of liver transplantation in patients with cholestatic liver disease. Hepatology. Mar 1997;25(3):672-7. [Medline].

  42. Roll J, Boyer JL, Barry D, et al. The prognostic importance of clinical and histologic features in asymptomatic and symptomatic primary biliary cirrhosis. N Engl J Med. Jan 6 1983;308(1):1-7. [Medline].

  43. Ros E, Garcia-Puges A, Reixach M, et al. Fat digestion and exocrine pancreatic function in primary biliary cirrhosis. Gastroenterology. Jul 1984;87(1):180-7. [Medline].

  44. Rutan G, Martinez AJ, Fieshko JT, et al. Primary biliary cirrhosis, Sjogren's syndrome, and transverse myelitis. Gastroenterology. Jan 1986;90(1):206-10. [Medline].

  45. Selinger S, Tsai J, Pulini M, et al. Autoimmune thrombocytopenia and primary biliary cirrhosis with hypoglycemia and insulin receptor autoantibodies. A case report. Ann Intern Med. Nov 1987;107(5):686-8. [Medline].

  46. Shapiro JM, Smith H, Schaffner F. Serum bilirubin: a prognostic factor in primary biliary cirrhosis. Gut. Feb 1979;20(2):137-40. [Medline].

  47. Thomas PK, Walker JG. Xanthomatous neuropathy in primary biliary cirrhosis. Brain. Dec 1965;88(5):1079-88. [Medline].

  48. Yamada G, Hyodo I, Tobe K, et al. Ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia in primary biliary cirrhosis. Hepatology. May-Jun 1986;6(3):385-91. [Medline].

 
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This histologic picture is compatible with stage 2 primary biliary cirrhosis.
 
 
 
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