scholarly journals Tuberculosis Is Not a Risk Factor for Primary Biliary Cirrhosis: A Review of the Literature

2012 ◽  
Vol 2012 ◽  
pp. 1-10
Author(s):  
Daniel S. Smyk ◽  
Dimitrios P. Bogdanos ◽  
Albert Pares ◽  
Christos Liaskos ◽  
Charalambos Billinis ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Primary Biliary Cirrhosis ◽  
Causal Relation ◽  
Association Studies ◽  
Epidemiologic Studies ◽  
High Titre ◽  
Molecular Evidence ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease characterised serologically by cholestasis and the presence of high-titre antimitochondrial antibodies, and histologically by chronic nonsuppurative cholangitis and granulomata. As PBC is a granulomatous disease andMycobacterium tuberculosisis the most frequent cause of granulomata, a causal relation between tuberculosis and PBC has been suggested. Attempts to find serological evidence of PBC-specific autoantibodies such as AMA have been made and, conversely, granulomatous livers from patients with PBC have been investigated for molecular evidence ofMycobacterium tuberculosis. This paper discusses in detail the reported data in support or against an association betweenMycobacterium tuberculosisinfection and PBC. We discuss the immunological and microbiological data exploring the association of PBC with exposure toMycobacterium tuberculosis. We also discuss the findings of large epidemiologic studies investigating the association of PBC with preexistent or concomitant disorders and the relevance of these findings with tuberculosis. Genome-wide association studies in patients with tuberculosis as well as in patients with PBC provide conclusive hints regarding the assumed association between exposure to this mycobacterium and the induction of PBC. Analysis of these data suggest thatMycobacterium tuberculosisis an unlikely infectious trigger of PBC.

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.

scholarly journals Genome-Wide Association Studies in Primary Biliary Cirrhosis

2015 ◽  
Vol 35 (04) ◽  
pp. 392-401 ◽  
Author(s):  
Aliya Gulamhusein ◽  
Brian Juran ◽  
Konstantinos Lazaridis
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Association Studies ◽  
Genome Wide Association ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Genetic Contribution to the Pathogenesis of Primary Biliary Cholangitis

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Satoru Joshita ◽  
Takeji Umemura ◽  
Eiji Tanaka ◽  
Masao Ota
Keyword(s):  
Association Studies ◽  
Disease Onset ◽  
Human Leukocyte ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies ◽  
Antimitochondrial Antibodies ◽  
Leukocyte Antigen ◽  
Genome Wide

Formerly termed primary biliary cirrhosis, primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease characterized by the presence of antimitochondrial antibodies. Ursodeoxycholic acid (UDCA) therapy is the most effective and approved treatment for PBC and leads to a favorable outcome in the vast majority of cases. Although the etiology of PBC has not yet been elucidated, human leukocyte antigen (HLA) class II alleles have been consistently associated with disease onset for decades. Individuals in different geographic regions of the world may have varying susceptibility alleles that reflect indigenous triggering antigens. In this review, we describe the influence of HLA alleles and other gene polymorphisms on PBC along with the results of genome-wide association studies (GWAS) on this disease.

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 Joint Analysis of Genetic Correlation, Mendelian Randomization and Colocalization Highlights the Bi-Directional Causal Association Between Hypothyroidism and Primary Biliary Cirrhosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanjun Wang ◽  
Ping Guo ◽  
Yanan Zhang ◽  
Lu Liu ◽  
Ran Yan ◽  
...  
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Genetic Correlation ◽  
Large Scale ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Joint Analysis ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies ◽  
Causal Association

Background: Hypothyroidism and primary biliary cirrhosis (PBC) are often co-existed in observational epidemiological studies. However, the causal relationship between them remains unclear.Methods: Genetic correlation, Mendelian randomization (MR) and colocalization analysis were combined to assess the potential causal association between hypothyroidism and PBC by using summary statistics from large-scale genome-wide association studies. Various sensitivity analyses had been conducted to assess the robustness and the consistency of the findings.Results: The linkage disequilibrium score regression demonstrated significant evidence of shared genetic architecture between hypothyroidism and PBC, with the genetic correlation estimated to be 0.117 (p = 0.006). The OR of hypothyroidism on PBC was 1.223 (95% CI, 1.072–1.396; p = 2.76 × 10−3) in MR analysis with inverse variance weighted (IVW) method. More importantly, the results from other 7MR methods with different model assumptions, were almost identical with that of IVW, suggesting the findings were robust and convincing. On the other hand, PBC was also causally associated with hypothyroidism (OR, 1.049; 95% CI, 1.010–1.089; p = 0.012), and, again, similar results can also be obtained from other MR methods. Various sensitivity analyses regarding the outlier detection and leave-one-out analysis were also performed. Besides, colocalization analysis suggested that there existed shared causal variants between hypothyroidism and PBC, further highlighting the robustness of the results.Conclusion: Our results suggest evidence for the bi-directional causal association between hypothyroidism and PBC, which may provide insights into the etiology of hypothyroidism and PBC as well as inform prevention and intervention strategies directed toward both diseases.

scholarly journals STAT4Gene Polymorphisms Are Associated with Susceptibility and ANA Status in Primary Biliary Cirrhosis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Satoru Joshita ◽  
Takeji Umemura ◽  
Minoru Nakamura ◽  
Yoshihiko Katsuyama ◽  
Soichiro Shibata ◽  
...  
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Genetic Factors ◽  
Association Studies ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
Genome Wide ◽  
Mitochondrial Antibody

Recent genome-wide association studies suggest that genetic factors contribute to primary biliary cirrhosis (PBC) susceptibility. Although several reports have demonstrated that the interleukin (IL) 12 signaling pathway is involved in PBC pathogenesis, its precise genetic factors have not been fully clarified. Here, we performed an association analysis betweenIL12A,IL12RB, andsignal transducer and activator of transcription 4 (STAT4)genetic variations and susceptibility to PBC. Single nucleotide polymorphisms (SNPs) were genotyped in 395 PBC patients and 458 healthy subjects of Japanese ethnicity and evaluated for associations with PBC susceptibility, anti-nuclear antibody (ANA) status, and anti-mitochondrial antibody (AMA) status. We detected significant associations with PBC susceptibility for severalSTAT4SNPs (rs10168266;P=9.4×10-3, rs11889341;P=1.2×10-3, rs7574865;P=4.0×10-4, rs8179673;P=2.0×10-4, and rs10181656;P=4.2×10-5). Three risk alleles (rs7574865;P=0.040, rs8179673;P=0.032, and rs10181656;P=0.031) were associated with ANA status, but not with AMA positivity. Our findings confirm thatSTAT4is involved in PBC susceptibility and may play a role in ANA status in the Japanese population.

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.

scholarly journals Recent advances in eosinophilic esophagitis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1775 ◽  
Author(s):  
Sandy Durrani ◽  
Marc Rothenberg
Keyword(s):  
Eosinophilic Esophagitis ◽  
Association Studies ◽  
Allergic Sensitization ◽  
Scoring Systems ◽  
Invasive Disease ◽  
Epidemiologic Studies ◽  
Genome Wide Association Studies ◽  
Monitoring Methods ◽  
Disease Pathogenesis ◽  
Meta Analyses

Eosinophilic esophagitis is a chronic, antigen-driven, eosinophil-predominant inflammatory disease of the esophagus and affects both children and adults. Cutting-edge technologies, such as genome-wide association studies, have advanced our understanding of the disease pathogenesis at a remarkable rate. Recent insights from genetic and mechanistic studies have concluded that a complex interplay between genetic and environmental risk factors, allergic sensitization, and esophageal-specific pathways leads to disease pathogenesis. Importantly, recent epidemiologic studies have found that the incidence and prevalence of eosinophilic esophagitis continue to rise. New guidelines have advocated the elimination of the term proton pump inhibitor (PPI)–responsive esophageal eosinophilia and have recommended using PPIs as a first-line treatment modality. Systemic reviews and meta-analyses confirm the efficacy of PPIs, topical corticosteroids, and empiric food elimination diets. Unmet needs include the development of birth cohort studies, validated diagnostic scoring systems, minimally invasive disease-monitoring methods, and the development of new therapies.

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