Sex Differences Associated with Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is a cholestatic liver disease of autoimmune origin, characterised by the destruction of small intrahepatic bile ducts. The disease has an unpredictable clinical course but may progress to fibrosis and cirrhosis. The diagnostic hallmark of PBC is the presence of disease-specific antimitochondrial antibodies (AMA), which are pathognomonic for the development of PBC. The disease overwhelmingly affects females, with some cases of male PBC being reported. The reasons underlying the low incidence of males with PBC are largely unknown. Epidemiological studies estimate that approximately 7–11% of PBC patients are males. There does not appear to be any histological, serological, or biochemical differences between male and female PBC, although the symptomatology may differ, with males being at higher risk of life-threatening complications such as gastrointestinal bleeding and hepatoma. Studies on X chromosome and sex hormones are of interest when studying the low preponderance of PBC in males; however, these studies are far from conclusive. This paper will critically analyze the literature surrounding PBC in males.

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E. coliInduced Experimental Model of Primary Biliary Cirrhosis: At Last

International Journal of Hepatology ◽

10.1155/2014/848373 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Andreas L. Koutsoumpas ◽

Daniel S. Smyk ◽

Dimitrios P. Bogdanos

Keyword(s):

Primary Biliary Cirrhosis ◽

Infected Animal ◽

Infectious Agent ◽

Epidemiological Studies ◽

Cholestatic Liver Disease ◽

Biliary Cirrhosis ◽

E Coli ◽

Intrahepatic Bile Ducts ◽

Additional Support ◽

Tract Infections

Recurrent urinary tract infections (UTI) have been considered potential triggers of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterised by progressive destruction of intrahepatic bile ducts. Additional support for the link made between PBC and UTI was based on early observations of recurrent episodes of bacteriuria in female patients with PBC. A series of large epidemiological studies demonstrated a strong correlation between recurrent UTI and PBC, initiating a series of studies investigating the role ofEscherichia coli(E. coli, the most prevalent organism isolated in women with UTI) as a trigger of PBC. Immunological evidence of B- and T-cell cross-reactive responses implicating PBC-specific autoantigens andE. colimimics have been clearly demonstrated, adding support to the notion thatE. coliis a potential infectious inducer of PBC in susceptible individuals. One of the major limitations in proving theE. coli/PBC association was the lack of reliableE. coli-infected animal models of PBC. This review provides an overview of the evidence linking this infectious agent with PBC and discusses the pros and cons of a recently developedE. coli-infected animal model of PBC.

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Primary biliary cirrhosis and myopathy: an uncommon association

Revista do Hospital das Clínicas ◽

10.1590/s0041-87811999000500007 ◽

1999 ◽

Vol 54 (5) ◽

pp. 165-168 ◽

Cited By ~ 5

Author(s):

Bruno Cupertino Migueletto ◽

Abrahão Elias Hallack Neto ◽

Elaine Zamora Domingues ◽

Pedro Paulo Neves de Castro ◽

Hartmut Stocker ◽

...

Keyword(s):

Liver Disease ◽

Primary Biliary Cirrhosis ◽

Bile Ducts ◽

Cholestatic Liver Disease ◽

Biliary Cirrhosis ◽

Muscular Weakness ◽

Muscular Diseases ◽

Histological Features ◽

Intrahepatic Bile Ducts ◽

Organ Systems

Primary biliary cirrhosis (PBC) is a cholestatic liver disease, which is characterized by a chronic inflammatory destruction of intrahepatic bile ducts. It is a rare disorder whose precise etiology is still to be elucidated. Even though the liver is the principal target of PBC, other organ systems also might be affected. Muscular involvement has rarely been described in this disease, and in the majority of cases, muscular weakness has been interpreted as polymyositis. We report the case of a 48-year-old woman suffering from classic PBC, in association with a myopathy whose histological features are distinct from the cases reported before. We also performed a MEDLINE research for PBC and concomitant muscular diseases.

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Rheumatoid Arthritis and Primary Biliary Cirrhosis: Cause, Consequence, or Coincidence?

Arthritis ◽

10.1155/2012/391567 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 11

Author(s):

Daniel S. Smyk ◽

Dimitrios P. Bogdanos ◽

Maria G. Mytilinaiou ◽

Andrew K. Burroughs ◽

Eirini I. Rigopoulou

Keyword(s):

Rheumatoid Arthritis ◽

Primary Biliary Cirrhosis ◽

High Titre ◽

Cholestatic Liver Disease ◽

Biliary Cirrhosis ◽

Infectious Agents ◽

Antimitochondrial Antibodies ◽

Genetic Studies ◽

Genetic Traits ◽

Large Case

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease characterized serologically by cholestasis and the presence of high-titre antimitochondrial antibodies and histologically by chronic nonsuppurative cholangitis and granulomata. PBC patients often have concomitant autoimmune diseases, including arthropathies. This raises the question as to whether there are shared features in the pathogenesis of those diseases with the pathogenesis of PBC. Epidemiological and large case studies have indicated that although the incidence of rheumatoid arthritis (RA) is not significantly raised in PBC patients, there appears to be a higher rate of RA in PBC patients and their relatives. Genetic studies have demonstrated that several genes implicated in PBC have also been implicated in RA. Epigenetic studies provided a wealth of data regarding RA, but the findings on epigenetic changes in PBC are very limited. As well, certain infectious agents identified in the pathogenesis of PBC may also play a role in the pathogenesis of RA. These data suggest that although RA is not significantly present in PBC, some individuals with certain genetic traits and environmental exposures may develop both conditions. This concept may also apply to other concomitant diseases found in PBC patients.

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Twelve-Year-Old Girl with Primary Biliary Cirrhosis

Case Reports in Pediatrics ◽

10.1155/2012/937150 ◽

2012 ◽

Vol 2012 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Ivana Kitic ◽

Aleksandra Boskovic ◽

Ivica Stankovic ◽

Dragan Prokic

Keyword(s):

Primary Biliary Cirrhosis ◽

World Literature ◽

Pediatric Patients ◽

Immunoglobulin M ◽

Cholestatic Liver Disease ◽

Biliary Cirrhosis ◽

Antimitochondrial Antibodies ◽

Biochemical Tests ◽

Autoimmune Etiology

Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic liver disease of autoimmune etiology. The initial presentation of PBC is varies from asymptomatic, abnormal liver biochemical tests to overt cirrhosis. Unlike other autoimmune liver diseases, PBC has rarely been reported in childhood. We report a case of primary biliary cirrhosis in a 12-year-old girl. In addition to characteristic histology features, strongly positive antimitochondrial antibodies, increased liver enzyme levels, increased serum quantitative immunoglobulin M levels, and cholestasis were discovered. She had been treated with ursodeoxycholic acid. In the world literature, we found only few pediatric patients of primary biliary cirrhosis. Aetiology, pathogenesis, the long-term natural history, and prognosis remain obscure. Due to increased awareness of early-onset PBC, rather than typical older ones, further pediatric cases may be discovered.

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Primary biliary cirrhosis

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.152103_update_001 ◽

2010 ◽

pp. 2464-2468

Author(s):

M.F. Bassendine ◽

D.E.J. Jones

Keyword(s):

Liver Disease ◽

Epithelial Cells ◽

Primary Biliary Cirrhosis ◽

Case History ◽

Bile Ducts ◽

Cholestatic Liver Disease ◽

Biliary Cirrhosis ◽

Blood Tests ◽

Intrahepatic Bile Ducts ◽

Immune Mediated

Case History—A 60 yr old woman presenting with abnormal liver blood tests. Primary biliary cirrhosis is a chronic, cholestatic liver disease in which the biliary epithelial cells lining the small intrahepatic bile ducts are the target for immune-mediated damage leading to progressive ductopenia. The cause is unknown, but presumed to be autoimmune....

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Oral Tolerance and Pyruvate Dehydrogenase in Patients with Primary Biliary Cirrhosis

Developmental Immunology ◽

10.1080/1044667021000098561 ◽

2002 ◽

Vol 9 (2) ◽

pp. 55-61 ◽

Cited By ~ 6

Author(s):

Ayako Suzuki ◽

Judy van de Water ◽

M. Eric Gershwin ◽

Roberta Jorgensen ◽

Paul Angulo ◽

...

Keyword(s):

Primary Biliary Cirrhosis ◽

Pyruvate Dehydrogenase ◽

Oral Tolerance ◽

Early Stage ◽

Pyruvate Dehydrogenase Complex ◽

Tolerance Induction ◽

Cholestatic Liver Disease ◽

Biliary Cirrhosis ◽

Antimitochondrial Antibodies ◽

Immunological Destruction

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the immunological destruction of intralobular bile ducts and serum anti-mitochondrial antibodies (AMA). Based upon previous work of oral tolerance and autoimmunity, we hypothesized that feeding the mitochondrial autoantigens of PBC would alter the clinical course and the level of antimitochondrial antibodies. The bovine pyruvate dehydrogenase complex (PDC) was purified and 5 mg fed in gelatin capsules to 6 patients with early stage PBC for 6 months. Antimitochondrial antibodies and liver biochemistries were measured at every 3 months for 12 months. The clinical trial was completed for all patients except for 1 who showed deterioration of pre-existing skin rash during treatment, which disappeared within 2 weeks after treatment was discontinued. However, after 1 year, neither the titers of AMAs nor liver biochemistries were significantly changed by this treatment. This is the first trial to test the efficacy of oral tolerance induction in PBC. However, the data, which limited in scope, did not demonstrate efficacy and further highlights the difficulties in showing continuing evidence of tolerance induction in autoimmunity.

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Xenobiotic Induced Model of Primary Biliary Cirrhosis

Serbian Journal of Experimental and Clinical Research ◽

10.2478/sjecr-2014-0019 ◽

2014 ◽

Vol 15 (3) ◽

pp. 145-150

Author(s):

Aleksandar Arsenijevic ◽

Jelena Milovanovic ◽

Bojana Stojanovic ◽

Marija Milovanovic ◽

Eric M. Gershwin ◽

...

Keyword(s):

Primary Biliary Cirrhosis ◽

Pyruvate Dehydrogenase ◽

Bile Ducts ◽

Pyruvate Dehydrogenase Complex ◽

Peptide Sequence ◽

Biliary Cirrhosis ◽

Murine Models ◽

Antimitochondrial Antibodies ◽

Immunodominant Epitope ◽

Intrahepatic Bile Ducts

Abstract Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver that is, characterised by destruction of the intrahepatic bile ducts and the presence of antimitochondrial antibodies (AMAs). Several murine models of PBC, with similar serological, biochemical, and histological features to human PBC, have been developed in recent years. These animal models enable investigators to study the etiology and pathophysiologic mechanism of PBC. Immune response in PBC is directed towards E2 components of the 2-oxo-acid dehydrogenase family of enzymes, which is in located in mitochondria and is an immunodominant epitope (a lipoylated peptide sequence shared by enzymes). Immunisation of mice with 2-octynoic acid coupled to bovine serum albumin (2-OA-BSA) (which is an antigen that is structurally related to the E2 subunit of the pyruvate dehydrogenase complex [PDC-E2]) produces histologic features similar to those found in human PBC. Th is model of xenobiotic induced PBC is suitable for studying the early events in PBC pathogenesis and for developing new therapeutics in PBC.

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Infection as a Risk Factor in the Pathogenesis of Primary Biliary Cirrhosis: Pros and Cons

Disease Markers ◽

10.1155/2010/791310 ◽

2010 ◽

Vol 29 (6) ◽

pp. 313-321 ◽

Cited By ~ 6

Author(s):

Teru Kumagi ◽

Masanori Abe ◽

Yoshiou Ikeda ◽

Yoichi Hiasa

Keyword(s):

Primary Biliary Cirrhosis ◽

Environmental Factors ◽

Molecular Mimicry ◽

Cholestatic Liver Disease ◽

Biliary Cirrhosis ◽

Infectious Agents ◽

Case Control Studies ◽

Intrahepatic Bile Ducts ◽

Genome Wide ◽

Pros And Cons

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology, characterized by injury of the intrahepatic bile ducts that may eventually lead to cirrhosis and liver failure. Evidence suggests cardinal roles for both environmental factors and genetic susceptibility. Nevertheless, the absolute etiology of PBC is unclear, despite recent well-designed case-control studies that reported environmental risk factors, including infectious agents, for PBC. Of the reported infectious agents, some of them are not reproducible and remain controversial. However, infection is no doubt one of the major risks among the environmental factors. This is supported by the fact that infectious agents in autoimmune diseases express antigens resulting in molecular mimicry and xenobiotics that play a role in breaking tolerance. Taken together, recent findings from genome wide assays as well as novel animal models may enable us to better understand the mechanism of pathogenesis responsible for this disease.

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A novel etiologic factor of highly elevated cholestanol levels: progressive familial intrahepatic cholestasis

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0314 ◽

2020 ◽

Vol 33 (5) ◽

pp. 665-669

Author(s):

Aynur Küçükçongar Yavaş ◽

Büşra Çavdarlı ◽

Özlem Ünal Uzun ◽

Ayşen Uncuoğlu ◽

Mehmet Gündüz

Keyword(s):

Primary Biliary Cirrhosis ◽

Intrahepatic Cholestasis ◽

Density Lipoprotein ◽

Etiologic Factor ◽

Compound Heterozygous ◽

Cholestatic Liver Disease ◽

Biliary Cirrhosis ◽

Progressive Familial Intrahepatic Cholestasis ◽

Turkish Patient ◽

Type 3

AbstractBackgroundProgressive familial intrahepatic cholestasis type 3 (PFIC3) is an uncommon cholestatic liver disease caused by mutations in the ATP binding cassette subfamily B member 4 (ABCB4) gene. Although PFIC3 is frequently identified in childhood, ABCB4 disease-causing alleles have been described in adults affected by intrahepatic cholestasis of pregnancy, hormone-induced cholestasis, low-phospholipid-associated cholelithiasis syndrome or juvenile cholelithiasis, cholangiocarcinoma and in sporadic forms of primary biliary cirrhosis. Cholestanol is a biomarker which is elevated especially in cerebrotendinous xanthomatosis and rarely in primary biliary cirrhosis (PBC) and Niemann Pick type C.Case presentationHere we report a Turkish patient with compound heterozygous mutations in the ABCB4 gene, who has hepatosplenomegaly, low level of high-density lipoprotein, cholestasis and high level of cholestanol.ConclusionThis is the first PFIC3 case with a high cholestanol level described in the literature. There are very few diseases linked to increased cholestanol levels, two of which are CTX and PBC. From this case, we can conclude that a high cholestanol level might be another indicator of PFIC type 3.

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