Primary biliary cirrhosis in a genetically homogeneous population: disease associations and familial occurrence rates.
BACKGROUND
Primary biliary cirrhosis (PBC) is a disease with genetic and environmental pathogenetic background. Chemicals, infectious agents, hormone therapy, reproductive history and surgical interventions have been implicated in the induction of PBC. Familial PBC has been documented in first degree relatives (FDR). Most cohort studies are genetically heterogeneous. Our study aimed to determine eventual lifestyle or disease associations and familial occurrence rates in a genetically homogeneous and geographically defined population of PBC patients.


METHODS
111 consenting PBC patients, were compared with 115 FDR and 149 controls matched for age, sex, Cretan origin and residence. All participants completed a questionnaire regarding demographics, lifestyle, medical, surgical and reproductive history. Significant variables on the univariate analysis were analyzed by multivariate analysis using a forward step-wise logistic regression model.


RESULTS
Dyslipidaemia was found in 69.4% of patients, 60% of FDR and 40.9% of controls (p < 0.0001 and p = 0.003 respectively), autoimmune diseases in 36.9% of patients, 30.4% of FDR and 13.4% of controls (p < 0.0001 and p = 0.011 respectively). Hashimoto's disease (p = 0.003), Raynaud syndrome (p = 0.023) and Sjögren syndrome (p = 0.044) were significantly associated with PBC. On multivariate analysis statistically significant associations were found with primary educational level (AOR 2.304, 95% CI 1.024-5.181), cholecystectomy (AOR 2.927, 95% CI 1.347-6.362) and the presence of at least another autoimmune disease (AOR 3.318, 95% CI 1.177-6.22). Cancer history was more frequent in patients than in controls (p = 0.033). Familial PBC was found to be 9.9%.


CONCLUSIONS
Dyslipidaemia and autoimmune diseases were significantly increased not only in patients as expected but also in their FDR. An increased prevalence of malignancies was found in patients. Primary educational level, cholecystectomy and the presence of at least another autoimmune disease were found as putative risk factors for PBC. No association was found with smoking, urinary tract infection or reproductive history. The reported high familial occurrence of PBC could imply screening with AMA of FDR with at least another autoimmune disease.
Department of Gastroenterology and Hepatology, University Hospital of Heraklion, P,O, BOX 1352, Heraklion, 71100, Crete, Greece. katmant@gmail.com
Aikaterini
A
Mantaka
Mairi
M
Koulentaki
Gregory
G
Chlouverakis
Jean Marie
JM
Enele-Melono
Aikaterini
A
Darivianaki
Maria
M
Tzardi
Elias A
EA
Kouroumalis
D000368:Aged; D001327:Autoimmune Diseases / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D002763:Cholecystectomy; D050171:Dyslipidemias / Q000453:epidemiology* / Q000235:genetics*; D004522:Educational Status; D005190:Family; D005260:Female; D006115:Greece; D050031:Hashimoto Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008019:Life Style; D008105:Liver Cirrhosis, Biliary / Q000453:epidemiology* / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011928:Raynaud Disease / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D012859:Sjogren's Syndrome / Q000453:epidemiology / Q000235:genetics