scholarly journals Environmental Agents Involved in the Cause of Primary Biliary Cirrhosis

2010 ◽  
Vol 29 (6) ◽  
pp. 329-336 ◽  
Author(s):  
Elias Kouroumalis
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Environmental Factors ◽  
Monozygotic Twins ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Infectious Agents ◽  
Immune Mediated ◽  
Environmental Agents ◽  
Autoimmune Conditions ◽  
Genetic And Environmental Factors

Primary biliary cirrhosis (PBC) is an immune mediated chronic cholestatic liver disease with a slowly progressive course It is a universal disease with a reported latitudinal gradient in prevalence and incidence. The aetiology of primary biliary cirrhosis is still unknown. It is characterized by a 60% concordance in monozygotic twins and is considered an autoimmune disease because of several features common to other autoimmune conditions and the relatively homogeneous serological and biochemical features. However geoepidemiological and clinical studies strongly imply that environmental factors also play an important role. It is accepted that the disease is clearly the result of a combination of genetic and environmental factors. Several risk factors have been suggested to be associated with PBC, including exposure to infectious agents and chemical xenobiotics. This review will attempt to place such factors in perspective.

scholarly journals Primary Biliary Cirrhosis: Family Stories

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Daniel Smyk ◽  
Evangelos Cholongitas ◽  
Stephen Kriese ◽  
Eirini I. Rigopoulou ◽  
Dimitrios P. Bogdanos
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Monozygotic Twins ◽  
Twin Studies ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Family Stories ◽  
Immune Mediated ◽  
Increased Risk ◽  
Environmental Component ◽  
High Concordance

Primary biliary cirrhosis (PBC) is a chronic immune-mediated cholestatic liver disease of unknown aetiology which affects mostly women in middle age. Familial PBC is when PBC affects more than one member of the same family, and data suggest that first-degree relatives of PBC patients have an increased risk of developing the disease. Most often, these familial clusters involve mother-daughter pairs, which is consistent with the female preponderance of the disease. These clusters provide evidence towards a genetic basis underlying PBC. However, clusters of nonrelated individuals have also been reported, giving strength to an environmental component. Twin studies have demonstrated a high concordance for PBC in monozygotic twins and a low concordance among dizygotic twins. In conclusion, studies of PBC in families clearly demonstrate that genetic, epigenetic, and environmental factors play a role in the development of the disease.

scholarly journals Infectious Agents and Xenobiotics in the Etiology of Primary Biliary Cirrhosis

2010 ◽  
Vol 29 (6) ◽  
pp. 287-299 ◽  
Author(s):  
Carlo Selmi ◽  
Maria De Santis ◽  
Francesca Cavaciocchi ◽  
M. Eric Gershwin
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Latitudinal Gradient ◽  
Monozygotic Twins ◽  
Review Article ◽  
Mitochondrial Proteins ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Infectious Agents ◽  
Environmental Stimulation ◽  
High Concordance

Primary biliary cirrhosis (PBC)is a chronic autoimmune cholestatic liver disease that manifests a latitudinal gradient in prevalence and incidence. The mechanisms leading to the initiation and perpetuation of PBC remain largely enigmatic, although it is established that a combination of genetic predisposition and environmental stimulation is required. PBC is also characterized by a high concordance rate in monozygotic twins and is considered a model autoimmune disease because of several features common to other conditions and the relatively homogeneous serological and biochemical features. From a diagnostic standpoint, PBC is characterized by the highest specificity of serum autoantibodies directed at mitochondrial proteins. Several risk factors have been suggested to be associated with PBC, including exposure to infectious agents and chemical xenobiotics that will be critically discussed in the present review article.

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

2010 ◽  
Vol 29 (6) ◽  
pp. 313-321 ◽  
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.

scholarly journals Primary Biliary Cirrhosis: Environmental Risk Factors

2010 ◽  
Vol 29 (6) ◽  
pp. 323-328 ◽  
Author(s):  
Deepti Dronamraju ◽  
Joseph Odin ◽  
Nancy Bach
Keyword(s):  
Risk Factors ◽  
Autoimmune Disease ◽  
Primary Biliary Cirrhosis ◽  
Monozygotic Twins ◽  
Northern Europe ◽  
Biliary Cirrhosis ◽  
Environmental Agents ◽  
Caucasian Women ◽  
Genetic And Environmental Factors ◽  
Unclear Etiology

Primary biliary cirrhosis (PBC) is an autoimmune disease of unclear etiology. It is a chronic, progressive condition that causes intrahepatic ductal destruction ultimately leading to symptoms of cholestasis, cirrhosis and liver failure. The disease predominantly affects middle aged Caucasian women. It has a predilection to certain regions and is found in higher incidences in North America and Northern Europe. It also has a genetic predisposition with a concordance rate of 60% among monozygotic twins. Combinations of genetic and environmental factors are proposed in the pathogenesis of this disease with a compelling body of evidence that suggests a role for both these factors. This review will elucidate data on the proposed environmental agents involved the disease's pathogenesis including xenobiotic and microbial exposure and present some of the supporting epidemiologic data.

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

Arthritis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
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.

Primary biliary cirrhosis

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....

scholarly journals Geographic Clusters of Primary Biliary Cirrhosis

2003 ◽  
Vol 10 (2-4) ◽  
pp. 127-131 ◽  
Author(s):  
Saif Abu-Mouch ◽  
Carlo Selmi ◽  
Gordon D. Benson ◽  
Thomas P. Kenny ◽  
Pietro Invernizzi ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Primary Biliary Cirrhosis ◽  
Environmental Factors ◽  
Small Area ◽  
Bile Ducts ◽  
Unknown Etiology ◽  
Biliary Cirrhosis ◽  
The Third ◽  
High Prevalence ◽  
Genetic And Environmental Factors

Genetic and environmental factors have been widely suggested to contribute to the pathogenesis of primary biliary cirrhosis (PBC), an autoimmune disease of unknown etiology leading to destruction of small bile ducts. Interestingly, epidemiologic data indicate a variable prevalence of the disease in different geographical areas. The study of clusters of PBC may provide clues as to possible triggers in the induction of immunopathology. We report herein four such unique PBC clusters that suggest the presence of both genetic and environmental factors in the induction of PBC. The first cluster is represented by a family of ten siblings of Palestinian origin that have an extraordinary frequency of PBC (with 5/8 sisters having the disease). Second, we describe the cases of a husband and wife, both having PBC. A family in which PBC was diagnosed in two genetically unrelated individuals, who lived in the same household, represents the third cluster. Fourth, we report a high prevalence of PBC cases in a very small area in Alaska. Although these data are anedoctal, the study of a large number of such clusters may provide a tool to estimate the roles of genetics and environment in the induction of autoimmunity.

scholarly journals Infectious Agents in the Pathogenesis of Primary Biliary Cirrhosis

2010 ◽  
Vol 29 (6) ◽  
pp. 277-286 ◽  
Author(s):  
Oscar-Danilo Ortega-Hernandez ◽  
Nancy-Agmon Levin ◽  
Arie Altman ◽  
Yehuda Shoenfeld
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Pyruvate Dehydrogenase ◽  
Molecular Mimicry ◽  
Pyruvate Dehydrogenase Complex ◽  
Amino Acid Sequences ◽  
Molecular Evidence ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Infectious Agents ◽  
Autoimmune Process

Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease which is characterized by the breakdown of self-tolerance to the highly conserved pyruvate dehydrogenase complex, specially the pyruvate dehydrogenase E2 complex (PDC-E2). The breakdown of the tolerance to such antigens leads to an autoimmune process characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Epidemiological studies have suggested that infections agents can trigger or even exacerbate the disease. Among other gram negative bacteria,Escherichia Coli, andNosphingobium aromaticivoransare the most associated agents reported hitherto. Epidemiological and molecular evidence points towards molecular mimicry between some components of these microorganisms and specific amino-acid sequences that are present in proteins on normal cells of the biliary tract. In this review, we revisit all reports suggesting that infectious agents might be associated with the autoimmune pathogenesis of PBC. We also retrieve the immune molecular mimicry mechanisms that are likely involved with the autoimmune process in PBC.

scholarly journals PBC Triggers in Water Reservoirs, Coal Mining Areas and Waste Disposal Sites: From Newcastle to New York

2010 ◽  
Vol 29 (6) ◽  
pp. 337-344 ◽  
Author(s):  
Daniel Smyk ◽  
Maria G. Mytilinaiou ◽  
Eirini I. Rigopoulou ◽  
Dimitrios P. Bogdanos
Keyword(s):  
New York ◽  
Primary Biliary Cirrhosis ◽  
Environmental Factors ◽  
Coal Mining ◽  
Waste Disposal ◽  
Geographical Area ◽  
Water Reservoir ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Increased Risk

Various environmental factors have been proposed as triggers of primary biliary cirrhosis (PBC), a progressive autoimmune cholestatic liver disease which is characterised by the destruction of the small intrahepatic bile ducts. Support for their pathogenic role in PBC is provided by epidemiological studies reporting familial clustering and clusters of the disease within a given geographical area. The seminal study by Triger reporting that the great majority of PBC cases in the English city of Sheffield drank water from a specific water reservoir, has been followed by studies reporting disease 'hot spots' within a restricted geographic region of the former coal mining area of Newcastle. The New York study reporting an increased risk and significant clustering of PBC cases near toxic federal waste disposal sites has added strength to the notion that environmental factors, possibly in the form of infectious agents or toxic/chemical environmental factors in areas of contaminated land, water or polluted air may play a key role in the development of the disease. This review discusses the findings of reports investigating environmental factors which may contribute to the cause of primary biliary cirrhosis.

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

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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