Environmental factors in primary biliary cirrhosis
Open accessAbstract
The etiology of the autoimmune liver disease primary biliary cirrhosis (PBC) remains largely unresolved, owing in large part to the complexity of interaction between environmental and genetic contributors underlying disease development. Observations of disease clustering, differences in geographical prevalence, and seasonality of diagnosis rates suggest the environmental component to PBC is strong, and epidemiological studies have consistently found cigarette smoking and history of urinary tract infection to be associated with PBC. Current evidence implicates molecular mimicry as a primary mechanism driving loss of tolerance and subsequent autoimmunity in PBC, yet other environmentally influenced disease processes are likely to be involved in pathogenesis. In this review, the authors provide an overview of current findings and touch on potential mechanisms behind the environmental component of PBC.
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Environmental factors likely interact with immunogenetic and epigenetic risk to drive PBC, favouring chronic immune-mediated biliary epithelial injury with cholestasis, ductopenia, and progressive biliary fibrosis.
“Environmental influences are likely to play a significant role in driving PBC, interacting with immunogenetic and epigenetic risk, favouring chronic immune mediated biliary epithelial injury with subsequent cholestasis, ductopenia, and progressive biliary fibrosis [11][12][13].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [11]
The Abstract and Concluding Remarks describe environmental exposures acting in genetically susceptible people, with loss of immune tolerance and subsequent biliary injury; the Abstract also describes chronic inflammation and destruction of biliary epithelial cells. The copy does not substantiate an interaction with epigenetic risk or the claimed sequence of cholestasis, ductopenia, and progressive biliary fibrosis. Its Smoking and Risk of Primary Biliary Cirrhosis section discusses an association with advanced fibrosis at presentation, not that sequence. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe existence of disease clustering points to environmental triggers, and research has supported both infectious and chemical triggers.
“The existence of disease clustering points to environmental triggers, and research has supported both infectious and chemical triggers.22 28 57–61”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [57]
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- Authors
- Juran, B., & Lazaridis, K.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Lazaridis, Konstantinos
- Venue
- Seminars in Liver Disease
- Publisher
- Georg Thieme Verlag KG
- Published
- 2014-07-24
- Volume
- 34
- Issue
- 03
- Pages
- 265-272
- ISSN
- 0272-8087 (ISSN-L)
- 1098-8971
- PMC
- PMC4232304
- OpenAlex
- W2033456588
- Cited by
- 89
- References
- 107
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 7 · 2023: 4 · 2022: 6 · 2021: 10 · 2020: 4 · 2019: 10 · 2018: 9 · 2017: 9 · 2016: 3 · 2015: 8
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Liver Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080670, R01 DK 80670)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Rheumatology › IgG4-Related and Inflammatory Diseases
- Keywords
- primary biliary cirrhosis, environmental risk factors, autoimmune liver disease, cigarette smoking, urinary tract infection, molecular mimicry, loss of immune tolerance, disease clustering, pathogenesis
- MeSH terms
- Bile Ducts, Intrahepatic, Environment, Humans, Life Style, Liver Cirrhosis, Biliary, Residence Characteristics, Risk Factors, Smoking, Urinary Tract Infections, Autoimmunity, Prevalence, Molecular Mimicry, Genetic Predisposition to Disease, Gene-Environment Interaction, Hygiene Hypothesis
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