| ?Background? Primary Biliary Cirrhosis or Primary Biliary Cholangitis(PBC) is a chronic autoimmune disease with positive serum antimitochondrial antibodies(AMA) and the immune-mediated progressive destruction of intra-hepatic bile ducts. Its pathogenesis remains largely unknown. It is hypothesized that PBC results from the broken of immune-tolerance triggered by interactions of genetic and environmental factors. Family history of PBC, high monozygotic twin concordance rate and human leucocyte antigen genotype may support the role of genetic factors in conferring susceptibility to PBC. However, environmental factors may trigger susceptible individuals and finally lead to the onset of PBC. Evidence for contribution of environmental factors includes time-space clustering of PBC prevalence, urinary tract infection and exposure to various chemicals such as hair dye usage and smoking. After the first case-control study of PBC relative factors was published in 1982, studied based on large cohorts were subsequently carried out, particularly during the last two decades. A variety of relative factors have been assumed in the development of PBC. Moreover, the psychological status has been identified as relative factors in several autoimmune diseases, while this association has not been reported in PBC.There is considerable variation in the prevalence of PBC worldwide, being most common in Northern Europe. A study conducted in Austria stated that migrant races from Italian, Greek, British and other countries were more likely to develop PBC compared to the native population. Another study in Southeast Asia with a very small sample size indicated a prevalence rate in Chinese subjects that was twice as high as that in the Malay population. Considering these findings, the PBC prevalence among the Chinese might not be low. However, data from Asia is rare. Therefore, we conducted a survey aimed at exploring the possible relative factors of PBC patients in Mid-west China.?Objectives? 1. To design a Primary Biliary Cirrhosis relative factor questionnaire; 2. To investigate the relative factors of PBC in Midwest China; 3. To investigate the PBC reproductive factors in the female patients.?Methods? 1. After the literature review, we summarize the published large scale PBC relative factors studies. Then we carried out the PBC relative factors questionnaire in Chinese in the group which include 8 liver experts, 1 statistical expert and 1 epidemiologist. And justify the items after the statistical analysis to ensure this questionnaire with high reliability and validity. We applied Spearman correlation to analyze the reliability. 2. Five hundred and thirty nine PBC patients who were consecutively referred to Xijing Hospital during October 2011 to May 2015. We invented them to participate in this study. And after excluding 4 PBC patients were diagnosed with AIH, PSC overlap syndrome; 11 refused; 3 suffered from hepatic encephalopathy and 9 have incomplete data after the twice telephone interviews. Finally there were 512 PBC patients were included in this study. We enrolled consecutive healthy controls from the Xijing Hospital Healthy Examination Register Database. The controls were matched based on gender, age±2 and residence location(province). After excluding incomplete data after the twice telephone interviews and the laboratory evidence suggested the potential liver damage ones. There were 761 volunteers from six provinces agreed to take part in the study.The Chinese 14-item perceived stress scales(CPSS) was applied to access the mental stress; the Satisfaction with life scale(SWLS) for the life satisfaction; the Pittsburgh sleep quality index(PSQI) for the quality of sleeping. In the relative factors section, univariate logistic regression was applied to analyze all variables. Variables that were significantly associated with PBC were entered into the multivariate binary logistic regression analysis. Two models were applied in the multivariate logistic regression analysis: a model for psychological status, lifestyle factors and medical station and another model for menstrual, reproductive station in female only. 3. We consecutively collected 273 female PBC patients referred to the Department of Gastroenterology, Xijing Hospital both in clinic and being admitted during October 2013 to August 2015. After excluding 3 PBC patients were diagnosed with AIH, PSC overlap syndrome; 11 refused; 2 suffer from hepatic encephalopathy and 7 have incomplete data after the twice telephone interviews; 207 have no female relatives in the siblings group. Finally there were 54 female PBC patients were included in PBC cases group, and the including ratio was 20%. We collected PBC relatives from October 2013 and must be in 10 years group with their specific PBC patients. After excluding the incomplete ones, the female PBC relative group consist of 88 PBC relatives after laboratory results excluding the PBC diagnosis. All PBC patients and their relatives gave the oral informed agreement. Student' t was applied to analyze the normally distributed continuous variables, and ?2 was applied to analyze classified variables. Dose response relationship was analyzed by multiple logistic regression analysis.?Results? 1. The questionnaire consists of 54-items. Two dimensions comprised the entire questionnaire: part A and part B. Part A focused on general characteristics(name, age, educational and financial levels). Part B consisted of five components regarding psychological, lifestyle, the medical history and menstrual and reproductive conditions in females. This questionnaire included all the published PBC relative factors and the possible items observed by liver experts in this group during the clinical practice, and theretest reliability in this questionnaire was 0.87. 2. Psychological stress(OR: 1.478; 95% CI: 1.038, 2.105); hair dye usage(OR: 1.644; 95% CI: 1.258, 2.147); allergy(OR: 1.688; 95% CI: 1.169, 2.437), urinary tract infection(OR: 2.232; 95% CI: 1.182, 4.214) and surgery(OR: 1.486; 95% CI: 1.092, 2.023); the number of live births(OR: 1.236, 95% CI: 1.083, 1.411), abnormal pregnancy(OR: 2.860; 95% CI: 1.645, 4.973) and pruritus during pregnancy(OR: 2.695, 95% CI: 1.273, 5.707) were significantly associated with increased risk of PBC. However, outdoors exposure time(OR: 0.928; 95% CI: 0.879, 0.980) may be a protective factor in the development of PBC. 3. In the analysis of PBC and siblings group, the mean number of live births in PBC group was(2.55±1.84), relatively bigger than in siblings group(1.84±0.95). Furthermore, there was an significant dose-response pattern for the live birth number and risk of PBC onset(P trend =0.002).?Conclusion? 1. Design the PBC relative factors questionnaire in Chinese and applied in the latter research. 2. Data in this study indicated that hair dye usage, allergy, urinary tract infection, surgery history, pruritus during pregnancy, number of live births and abnormal pregnancy may be relative factors of the development. And we found that high psychological stress may be PBC relative factor but outdoor exposure time turn out to be a protective factor. 3. This study discovered that number of live births may be relative factor of the PBC development. Furthermore, number of live births may affect the development of PBC in the dose response method. |
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