Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview‐based study of 1032 patients
Open accessAbstract
Primary biliary cirrhosis (PBC) is an autoimmune disease of unknown etiology, often associated with other autoimmune conditions. Controlled studies have so far provided conflicting data on risk factors and comorbidity rates in PBC. We enrolled patients with PBC (n = 1032) from 23 tertiary referral centers for liver diseases in the United States and random-digit-dialed controls (n = 1041) matched for sex, age, race, and geographical location. Patients and controls were administered a modified version of the US National Health and Nutrition Examination Study (NHANES III) questionnaire by trained personnel to evaluate associations between PBC and social, demographic, personal and family medical histories, lifestyle, and reproductive factors and the rates of comorbidity in affected individuals. Data indicate that having a first-degree relative with PBC (adjusted odds ratio [AOR] 10.736; 95% confidence interval 4.227-27.268), history of urinary tract infections (AOR 1.511, 95% CI 1.192-1.915), past smoking (AOR 1.569, 95% CI 1.292-1.905), or use of hormone replacement therapies (AOR 1.548, 95% CI 1.273-1.882) were significantly associated with increased risk of PBC. The frequent use of nail polish slightly increased the risk of having PBC. Other autoimmune diseases were found in 32% of cases and 13% of controls (P<0.0001). In conclusion , environmental factors, possibly including infectious agents through urinary tract infections or chemicals contained in cigarette smoke, may induce PBC in genetically susceptible individuals. Exogenous estrogens may also contribute to explain the female predominance of the disease. (Hepatology 2005;42:1194–1202.)
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Patients with PBC typically have an increased incidence, in both themselves and their families, of other autoimmune diseases (over half of patients with PBC have another autoimmune condition).
“Patients with PBC typically have an increased incidence, in both themselves and their families, of other autoimmune diseases (over half of patients with PBC have another autoimmune condition), reflecting shared genetic predisposition (most notably but not exclusively celiac disease, scleroderma, thyroid disease and Sjögren’s).37–43”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [40]
The Discussion reports more autoimmune comorbidity in patients with PBC than in controls, and the Family History section reports increased rates of several autoimmune diseases among relatives. But the Discussion gives the rate in patients as 32%, not over half. It treats genetic predisposition as a hypothesis and does not establish the sentence’s reference to celiac disease. (LLM, conf=0.91)
Experimental — accuracy not yet measuredCase-control study approaches have confirmed cigarette smoking and recurrent urinary tract infections (UTIs) as being strongly associated with PBC; cholestasis and/or pruritus during prior pregnancy is also associated with future diagnosis of PBC.
“Case–control study approaches, which explore risk history in patients and matched controls, have confirmed cigarette smoking and recurrent urinary tract infections (UTIs) as being strongly associated with PBC; cholestasis and/or pruritus during prior pregnancy is also associated with future diagnosis of PBC.40 42 43 62”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [40]
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredLarge case-control studies have associated PBC with urinary tract infections, reproductive hormone replacement, nail polish, and past cigarette smoking.
“Environmental risks have been suggested by several large case-control cohort studies that have found associations with urinary tract infections, reproductive hormone replacement, nail polish, and past cigarette smoking.(22)(23)(24)”
From Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases (2019) · cites this paper as [24]
Large case-control studies have associated PBC with urinary tract infections, reproductive hormone replacement, nail polish, and past cigarette smoking.
“Environmental risks have been suggested by several large case-control cohort studies that have found associations with urinary tract infections, reproductive hormone replacement, nail polish, and past cigarette smoking.(22)(23)(24)”
From Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases (2019) · cites this paper as [23]
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Invernizzi, P., Alessio, M. G., Smyk, D. S., Lleo, A., Sonzogni, A., Fabris, L., Candusso, M., Bogdanos, D. P., Iorio, R., & Torre, G. (2012) · BMC Gastroenterology · doi:10.1186/1471-230x-12-92 · Cited by 28 · see citing works
Li, Q., Patrick, M. T., Sreeskandarajan, S., Kang, J., Kahlenberg, J. M., Gudjonsson, J. E., He, Z., & Tsoi, L. C. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1309549 · Cited by 22 · see citing works
The immunological landscape of primary biliary cholangitis: Mechanisms and therapeutic prospects
Ronca, V., Davies, S. P., Oo, Y. H., & Lleo, A. (2025) · Hepatology · doi:10.1097/hep.0000000000001225 · Cited by 22 · see citing works
- Authors
- Gershwin, E. M., Selmi, C., Worman, H. J., Gold, E. B., Watnik, M., Utts, J., Lindor, K. D., Kaplan, M. M., & Vierling, J. M.
- Affiliations
- University of California, Davis (US)
- University of Milan (IT)
- Columbia University (US)
- Mayo Clinic (US)
- Tufts Medical Center (US)
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Gershwin, Eric M.
- ORCID
- Venue
- Hepatology
- Published
- 2005-11
- Volume
- 42
- Issue
- 5
- Pages
- 1194-1202
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC3150736
- OpenAlex
- W2059378625
- Cited by
- 621
- References
- 40
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 29 · 2023: 36 · 2022: 30 · 2021: 22 · 2020: 25 · 2019: 30 · 2018: 40 · 2017: 39 · 2016: 24 · 2015: 34 · 2014: 27 · 2013: 32 · 2012: 43
- FWCI
- 15.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Northwestern University
- University of Minnesota
- University of Washington
- Ochsner Health
- University of California, San Francisco
- National Institute of Diabetes and Digestive and Kidney Diseases (DK56839, R01DK056839)
- 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, risk factors, comorbidities, autoimmune disease, family history (medicine), urinary tract infection, smoking, hormone replacement therapy, nail polish, environmental risk factors, exogenous estrogen, female predominance, genetic susceptibility
- MeSH terms
- Aged, Anthropometry, Demography, Female, Humans, Interviews as Topic, Life Style, Liver Cirrhosis, Biliary, Male, Medical Records, Middle Aged, Nutrition Surveys, Surveys and Questionnaires, Risk Factors, Case-Control Studies, Reproductive Medicine
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