biliary liver cirrhosis

Summary

Summary: FIBROSIS of the hepatic parenchyma due to obstruction of BILE flow (CHOLESTASIS) in the intrahepatic or extrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC; BILE DUCTS, EXTRAHEPATIC). Primary biliary cirrhosis involves the destruction of small intra-hepatic bile ducts and bile secretion. Secondary biliary cirrhosis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes.

Top Publications

  1. Gershwin M, Mackay I. The causes of primary biliary cirrhosis: Convenient and inconvenient truths. Hepatology. 2008;47:737-45 pubmed
    ..We present these data under the umbrella of convenient truths that support this thesis as well as some inconvenient truths that are not readily accommodated by current theory...
  2. Padgett K, Lan R, Leung P, Lleo A, Dawson K, Pfeiff J, et al. Primary biliary cirrhosis is associated with altered hepatic microRNA expression. J Autoimmun. 2009;32:246-53 pubmed publisher
    ..Our data are the first to demonstrate that PBC is characterized by altered expression of hepatic miRNA; however additional studies are required to demonstrate a causal link between those miRNA and the development of PBC...
  3. Lleo A, Invernizzi P, Mackay I, Prince H, Zhong R, Gershwin M. Etiopathogenesis of primary biliary cirrhosis. World J Gastroenterol. 2008;14:3328-37 pubmed
    ..In this article, we critically review the available evidence on etiopathogenesis of PBC and present interpretations of complex data, new developments and theories, and nominate directions for future research...
  4. Selmi C, Zuin M, Gershwin M. The unfinished business of primary biliary cirrhosis. J Hepatol. 2008;49:451-60 pubmed publisher
    ..However, this research has still not led to successful translation for specific therapy...
  5. Huet P, Vincent C, Deslaurier J, Cote J, Matsutami S, Boileau R, et al. Portal hypertension and primary biliary cirrhosis: effect of long-term ursodeoxycholic acid treatment. Gastroenterology. 2008;135:1552-60 pubmed publisher
    ..The aim of the study was to determine the prevalence and prognostic value of portal hypertension in patients treated with ursodeoxycholic acid...
  6. Poupon R, Ping C, Chretien Y, Corpechot C, Chazouilleres O, Simon T, et al. Genetic factors of susceptibility and of severity in primary biliary cirrhosis. J Hepatol. 2008;49:1038-45 pubmed publisher
  7. Moritoki Y, Zhang W, Tsuneyama K, Yoshida K, Wakabayashi K, Yang G, et al. B cells suppress the inflammatory response in a mouse model of primary biliary cirrhosis. Gastroenterology. 2009;136:1037-47 pubmed publisher
    ..Mice that express a dominant-negative form of transforming growth factor-beta receptor restricted to T cells (dnTGF-betaRII) develop antimitochondrial antibodies and liver inflammation similar to human primary biliary cirrhosis...
  8. Bauer A, Habior A. Measurement of gp210 autoantibodies in sera of patients with primary biliary cirrhosis. J Clin Lab Anal. 2007;21:227-31 pubmed
    ..The results were negative for healthy blood donors and other controls. The specificity of the test was 99%, so the anti-gp-210 autoantibodies estimated on DRKASPPSGLWSPAY can be a reliable marker of PBC...
  9. Jones D. Pathogenesis of primary biliary cirrhosis. Gut. 2007;56:1615-24 pubmed

More Information

Publications62

  1. Bogdanos D, Pusl T, Rust C, Vergani D, Beuers U. Primary biliary cirrhosis following Lactobacillus vaccination for recurrent vaginitis. J Hepatol. 2008;49:466-73 pubmed publisher
    ..We report a case of symptomatic PBC diagnosed after sequential immunization with a lactobacillus vaccine for recurrent vaginitis over years...
  2. Leung P, Park O, Tsuneyama K, Kurth M, Lam K, Ansari A, et al. Induction of primary biliary cirrhosis in guinea pigs following chemical xenobiotic immunization. J Immunol. 2007;179:2651-7 pubmed
  3. Salas J, Banales J, Sarvide S, Recalde S, Ferrer A, Uriarte I, et al. Ae2a,b-deficient mice develop antimitochondrial antibodies and other features resembling primary biliary cirrhosis. Gastroenterology. 2008;134:1482-93 pubmed publisher
    ..In mice with widespread Ae2 gene disruption, we previously reported altered spermiogenesis and reduced gastric acid secretion. We now describe the hepatobiliary and immunologic changes observed in these Ae2(a.b)-deficient mice...
  4. Schott E, Witt H, Pascu M, van Boemmel F, Weich V, Bergk A, et al. Association of CTLA4 single nucleotide polymorphisms with viral but not autoimmune liver disease. Eur J Gastroenterol Hepatol. 2007;19:947-51 pubmed
    ..In reverse form, CTLA4 variations are associated with chronic infections such as chronic hepatitis B...
  5. Juran B, Atkinson E, Schlicht E, Fridley B, Petersen G, Lazaridis K. Interacting alleles of the coinhibitory immunoreceptor genes cytotoxic T-lymphocyte antigen 4 and programmed cell-death 1 influence risk and features of primary biliary cirrhosis. Hepatology. 2008;47:563-70 pubmed
    ..As well, we identified the influence of an interaction between the putatively autoimmune-protective CTLA4 49AG:CT60 AA haplotype and autoimmune-risk PDCD1 PD1.3 A allele on development of PBC...
  6. Wesierska Gadek J, Klima A, Ranftler C, Komina O, Hanover J, Invernizzi P, et al. Characterization of the antibodies to p62 nucleoporin in primary biliary cirrhosis using human recombinant antigen. J Cell Biochem. 2008;104:27-37 pubmed
  7. Newton J, Hudson M, Tachtatzis P, Sutcliffe K, Pairman J, Burt J, et al. Population prevalence and symptom associations of autonomic dysfunction in primary biliary cirrhosis. Hepatology. 2007;45:1496-505 pubmed
    ..3, P < .0001). Thirteen of 20 patients with an OGS value > 4 (moderate severity and worse) had significant abnormality in autonomic regulation of blood pressure, which was identified on dynamic testing...
  8. Leung P, Rossaro L, Davis P, Park O, Tanaka A, Kikuchi K, et al. Antimitochondrial antibodies in acute liver failure: implications for primary biliary cirrhosis. Hepatology. 2007;46:1436-42 pubmed
    ..1% of ALF patients)...
  9. Wesierska Gadek J, Klima A, Komina O, Ranftler C, Invernizzi P, Penner E. Characterization of autoantibodies against components of the nuclear pore complexes: high frequency of anti-p62 nucleoporin antibodies. Ann N Y Acad Sci. 2007;1109:519-30 pubmed
    ..Considering the recently reported clinical significance of ANAs in PBC, the prognostic value of the anti-NPC antibodies and their correlation with severity and progression of the disease is under evaluation...
  10. Invernizzi P, Selmi C, Poli F, Frison S, Floreani A, Alvaro D, et al. Human leukocyte antigen polymorphisms in Italian primary biliary cirrhosis: a multicenter study of 664 patients and 1992 healthy controls. Hepatology. 2008;48:1906-12 pubmed publisher
    ..We suggest that a large whole-genome approach is required to identify further genetic elements contributing to the loss of tolerance in this disease...
  11. Hirschfield G, Liu X, Xu C, Lu Y, Xie G, Lu Y, et al. Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N Engl J Med. 2009;360:2544-55 pubmed publisher
    ..Twin and family aggregation data suggest that there is a significant genetic predisposition to primary biliary cirrhosis, but the susceptibility loci are unknown...
  12. Kuiper E, Hansen B, de Vries R, den Ouden Muller J, van Ditzhuijsen T, Haagsma E, et al. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology. 2009;136:1281-7 pubmed publisher
    ..We performed a prospective multicenter study of patients with PBC treated with UDCA to compare prognosis with biochemical response...
  13. Shimoda S, Miyakawa H, Nakamura M, Ishibashi H, Kikuchi K, Kita H, et al. CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis. J Autoimmun. 2008;31:110-5 pubmed publisher
    ..These observations emphasize that the mitochondrial autoreactivity in PBC is a multi-lineage response and hence, AMA-negative PBC may be an anachronism that refers only to sera autoantibodies...
  14. Corpechot C, Abenavoli L, Rabahi N, Chretien Y, Andreani T, Johanet C, et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology. 2008;48:871-7 pubmed publisher
    ..3). Antinuclear antibodies against gp210 or Sp100 proteins were associated with death or LT in univariate but not in multivariate analysis...
  15. Lan R, Salunga T, Tsuneyama K, Lian Z, Yang G, Hsu W, et al. Hepatic IL-17 responses in human and murine primary biliary cirrhosis. J Autoimmun. 2009;32:43-51 pubmed publisher
  16. Lleo A, Selmi C, Invernizzi P, Podda M, Coppel R, Mackay I, et al. Apotopes and the biliary specificity of primary biliary cirrhosis. Hepatology. 2009;49:871-9 pubmed publisher
    ..The fact that AMA-containing sera reacted with PDC-E2 on apoptotic BECs without a requirement for permeabilization suggests that the autoantigen is accessible to the immune system during apoptosis...
  17. Arenas F, Hervias I, Uriz M, Joplin R, Prieto J, Medina J. Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J Clin Invest. 2008;118:695-709 pubmed publisher
    ..Our data provide a potential molecular explanation for the beneficial effects of the combination of UDCA and glucocorticoids in PBC patients with inadequate response to UDCA monotherapy...
  18. Shimoda S, Harada K, Niiro H, Yoshizumi T, Soejima Y, Taketomi A, et al. Biliary epithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells. Hepatology. 2008;47:958-65 pubmed publisher
    ..Furthermore, the addition of autologous LMNCs to PBC BECs led to the production of higher levels of chemokines and enhanced the expression of CD40 and HLA-DRalpha...
  19. Liu B, Shi X, Zhang F, Zhang W, Gao L. Antimitochondrial antibody-negative primary biliary cirrhosis: a subset of primary biliary cirrhosis. Liver Int. 2008;28:233-9 pubmed publisher
    ..This study aimed to evaluate whether AMA-negative/positive PBC represents different clinical entities...
  20. Allina J, Stanca C, Garber J, Hu B, Sautes Fridman C, Bach N, et al. Anti-CD16 autoantibodies and delayed phagocytosis of apoptotic cells in primary biliary cirrhosis. J Autoimmun. 2008;30:238-45 pubmed
    ..050). In conclusion, PBC macrophage phagocytosis of opsonized apoptotic cells is impaired, irrespective of serum factors and may increase hepatic inflammation...
  21. Su T, Hwang J, Kao J. Hypercholesterolemia in primary biliary cirrhosis. N Engl J Med. 2007;357:1561-2 pubmed
  22. McDermid J, Chen M, Li Y, Wasilenko S, Bintner J, McDougall C, et al. Reverse transcriptase activity in patients with primary biliary cirrhosis and other autoimmune liver disorders. Aliment Pharmacol Ther. 2007;26:587-95 pubmed
    ..Patients with biliary disease make retroviral antibodies and the Human Betaretrovirus has been characterized in patients with primary biliary cirrhosis...
  23. Beuers U. Crosstalk of liver, bile ducts and the gut. Clin Rev Allergy Immunol. 2009;36:1-3 pubmed publisher
    ..Potential molecular targets for future therapeutic approaches are also addressed...
  24. Jones D. Pathogenesis of primary biliary cirrhosis. Clin Liver Dis. 2008;12:305-21; viii pubmed publisher
    ..Alternative (but not necessary mutually exclusive) pathogenetic models have been outlined, including a potential role for retroviral pathogens and directly cytopathic effects...
  25. Gao L, Tian X, Liu B, Zhang F. The value of antinuclear antibodies in primary biliary cirrhosis. Clin Exp Med. 2008;8:9-15 pubmed publisher
    ..Although autoantibodies have been used for the diagnosis of primary biliary cirrhosis (PBC), their role has not been clarified. In this study, we try to explore the value of gp210 antibody and anti-centromere antibodies (ACA) in PBC...
  26. Invernizzi P, Gershwin M. The genetic basis of primary biliary cirrhosis: premises, not promises. Gastroenterology. 2008;135:1044-7 pubmed publisher
  27. Newton J, Pairman J, Sutcliffe K, Wilton K, Jones D. A predictive model for fatigue and its etiologic associations in primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2008;6:228-33 pubmed publisher
    ..Here we explore how these biological associates inter-relate, and their cumulative impact upon typical clinical cohorts...
  28. Kaplan M, Gershwin M. Primary biliary cirrhosis. N Engl J Med. 2005;353:1261-73 pubmed
  29. Chuang Y, Lian Z, Cheng C, Lan R, Yang G, Moritoki Y, et al. Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives. J Autoimmun. 2005;25:126-32 pubmed
    ..Our data imply a role for specific chemokine-chemokine receptor interactions in the pathogenesis of PBC and also highlight the familial risk factor...
  30. Mao T, Lian Z, Selmi C, Ichiki Y, Ashwood P, Ansari A, et al. Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis. Hepatology. 2005;42:802-8 pubmed
  31. Nakamura M, Takii Y, Ito M, Komori A, Yokoyama T, Shimizu Yoshida Y, et al. Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis. J Autoimmun. 2006;26:138-45 pubmed
  32. Lee Y, Kaplan M. The natural history of PBC: has it changed?. Semin Liver Dis. 2005;25:321-6 pubmed
    ..However, patients with stage III and IV PBC do not respond as well to UDCA. Therefore, there is a continued need for additional treatment in patients with advanced disease...
  33. Jung Y, McCall S, Li Y, Diehl A. Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis. Hepatology. 2007;45:1091-6 pubmed
    ..The number of Ihh+ cells/portal triad was 6-fold greater in PBC livers than controls (P<0.05). OV6+ progenitors increased significantly in PBC livers, and some of these cells coexpressed Ihh, Ptc, and/or Gli2...
  34. Corpechot C, El Naggar A, Poujol Robert A, Ziol M, Wendum D, Chazouilleres O, et al. Assessment of biliary fibrosis by transient elastography in patients with PBC and PSC. Hepatology. 2006;43:1118-24 pubmed
    ..In conclusion, transient elastography is a simple and reliable noninvasive means for assessing biliary fibrosis. It should be a promising tool to assess antifibrotic therapies in PBC or PSC...
  35. Jones D, Newton J. An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis. Aliment Pharmacol Ther. 2007;25:471-6 pubmed
    ..The CNS-acting drug modafinil has an established role in the treatment of excessive daytime somnolence in non-liver disease states...
  36. Zein C, Beatty K, Post A, Logan L, Debanne S, McCullough A. Smoking and increased severity of hepatic fibrosis in primary biliary cirrhosis: A cross validated retrospective assessment. Hepatology. 2006;44:1564-71 pubmed
    ..In conclusion, smoking may accelerate the progression of PBC. This could be induced by exposure to chemicals in cigarette smoke...
  37. Granito A, Muratori P, Muratori L, Pappas G, Cassani F, Worthington J, et al. Antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns: diagnostic accuracy for primary biliary cirrhosis. Aliment Pharmacol Ther. 2006;24:1575-83 pubmed
    ..Serum antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns are frequently detected by indirect immunofluorescence on HEp-2 cells in patients with primary biliary cirrhosis...
  38. Yokomori H, Oda M, Ogi M, Wakabayashi G, Kawachi S, Yoshimura K, et al. Expression of adhesion molecules on mature cholangiocytes in canal of Hering and bile ductules in wedge biopsy samples of primary biliary cirrhosis. World J Gastroenterol. 2005;11:4382-9 pubmed
  39. Giorgini A, Selmi C, Invernizzi P, Podda M, Zuin M, Gershwin M. Primary biliary cirrhosis: solving the enigma. Ann N Y Acad Sci. 2005;1051:185-93 pubmed
    ..In this review, available data and current theories regarding the immunomediated pathogenesis of PBC will be described...
  40. Vierling J. Future Treatment Options in PBC. Semin Liver Dis. 2005;25:347-63 pubmed
    ..Induction of tolerance in susceptible people before onset of disease or of hyporesponsiveness in established disease is increasingly feasible, as is prevention of biliary fibrosis...
  41. Allina J, Hu B, Sullivan D, Fiel M, Thung S, Bronk S, et al. T cell targeting and phagocytosis of apoptotic biliary epithelial cells in primary biliary cirrhosis. J Autoimmun. 2006;27:232-41 pubmed
    ..BECs have the ability to present novel mitochondrial self-peptides derived from phagocytosed apoptotic BECs. Apoptotic cell phagocytosis by non-professional phagocytes may influence the tissue specificity of autoimmune diseases...
  42. Wesierska Gadek J, Penner E, Battezzati P, Selmi C, Zuin M, Hitchman E, et al. Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis. Hepatology. 2006;43:1135-44 pubmed
    ..5%, P = .019). Anti-NPC antibodies remained stable or slightly increased over the period of observation. In condusion, anti-NPC identifies patients likely to experience an unfavorable clinical course and more rapid disease progression...
  43. Babatin M, Sanai F, Swain M. Methotrexate therapy for the symptomatic treatment of primary biliary cirrhosis patients, who are biochemical incomplete responders to ursodeoxycholic acid therapy. Aliment Pharmacol Ther. 2006;24:813-20 pubmed
    ..Although it has been shown to improve biochemical markers and delay disease progression, its effect upon fatigue and pruritus, is at best uncertain...
  44. Milkiewicz P, Heathcote J. Primary biliary cirrhosis in a patient with Turner syndrome. Can J Gastroenterol. 2005;19:631-3 pubmed
    ..The present case may support the importance of X chromosome genes in the development of genetic predisposition to PBC, and emphasizes the necessity for a systematic study of the prevalence of PBC in patients with Turner syndrome...
  45. Pares A, Caballeria L, Rodes J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic Acid. Gastroenterology. 2006;130:715-20 pubmed
  46. ter Borg P, Schalm S, Hansen B, van Buuren H. Prognosis of ursodeoxycholic Acid-treated patients with primary biliary cirrhosis. Results of a 10-yr cohort study involving 297 patients. Am J Gastroenterol. 2006;101:2044-50 pubmed
    ..The aim of the present study was to document long-term survival of a prospectively followed large cohort of UDCA treated patients in comparison to that predicted by the Mayo model and of a matched control cohort of the Dutch population...
  47. Talwalkar J, Donlinger J, Gossard A, Keach J, Jorgensen R, Petz J, et al. Fluoxetine for the treatment of fatigue in primary biliary cirrhosis: a randomized, double-blind controlled trial. Dig Dis Sci. 2006;51:1985-91 pubmed
    ..Three of the four patients had drug-related adverse events with fluoxetine. In this study, fluoxetine did not improve fatigue in PBC and was associated with adverse events...
  48. Zein C, Jorgensen R, Clarke B, Wenger D, Keach J, Angulo P, et al. Alendronate improves bone mineral density in primary biliary cirrhosis: a randomized placebo-controlled trial. Hepatology. 2005;42:762-71 pubmed
    ..Although in this study oral alendronate appears to be well tolerated in patients with PBC, larger studies are needed to formally evaluate safety...
  49. Gershwin M, Selmi C, Worman H, Gold E, Watnik M, Utts J, et al. Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients. Hepatology. 2005;42:1194-202 pubmed
    ..Exogenous estrogens may also contribute to explain the female predominance of the disease...
  50. Oertelt S, Lian Z, Cheng C, Chuang Y, Padgett K, He X, et al. Anti-mitochondrial antibodies and primary biliary cirrhosis in TGF-beta receptor II dominant-negative mice. J Immunol. 2006;177:1655-60 pubmed
  51. Gong Y, Huang Z, Christensen E, Gluud C. 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 pubmed
    ..Ursodeoxycholic acid (UDCA) is used for primary biliary cirrhosis (PBC), but the beneficial effects remain controversial...
  52. Selmi C, Invernizzi P, Zuin M, Podda M, Seldin M, Gershwin M. Genes and (auto)immunity in primary biliary cirrhosis. Genes Immun. 2005;6:543-56 pubmed
  53. Liu H, Deng A, Zhang J, Zhou Y, Yao D, Shen F, et al. [Analysis of HLA alleles polymorphism in Chinese patients with primary biliary cirrhosis]. Zhonghua Gan Zang Bing Za Zhi. 2005;13:410-3 pubmed