Potential Roles for Infectious Agents in the Pathophysiology of Primary Biliary Cirrhosis: What’s New?

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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Infectious Agents and Xenobiotics in the Etiology of Primary Biliary Cirrhosis

Disease Markers ◽

10.1155/2010/752314 ◽

2010 ◽

Vol 29 (6) ◽

pp. 287-299 ◽

Cited By ~ 28

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.

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Environmental Agents Involved in the Cause of Primary Biliary Cirrhosis

Disease Markers ◽

10.1155/2010/824396 ◽

2010 ◽

Vol 29 (6) ◽

pp. 329-336 ◽

Cited By ~ 1

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.

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Primary Biliary Cirrhosis and E. coli-induced Pyelonephritis; Are Infectious Agents Related to the Pathogenesis of Primary Biliary Cirrhosis?

Internal Medicine ◽

10.2169/internalmedicine.42.1063 ◽

2003 ◽

Vol 42 (11) ◽

pp. 1063-1064

Author(s):

Hiroto KITA

Keyword(s):

Primary Biliary Cirrhosis ◽

Biliary Cirrhosis ◽

Infectious Agents ◽

E Coli

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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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Are infectious agents involved in primary biliary cirrhosis? A PCR approach

Journal of Hepatology ◽

10.1016/s0168-8278(99)80346-8 ◽

1999 ◽

Vol 31 (4) ◽

pp. 664-671 ◽

Cited By ~ 55

Author(s):

Atsushi Tanaka ◽

Thomas P Prindiville ◽

Robert Gish ◽

Jay V Solnick ◽

Ross L Coppel ◽

...

Keyword(s):

Primary Biliary Cirrhosis ◽

Biliary Cirrhosis ◽

Infectious Agents

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Infectious Agents in the Pathogenesis of Primary Biliary Cirrhosis

Disease Markers ◽

10.1155/2010/923928 ◽

2010 ◽

Vol 29 (6) ◽

pp. 277-286 ◽

Cited By ~ 13

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.

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