Determinants for gallstone formation – a new data cohort study and a systematic review with meta-analysis*

<b>Objective:</b> Only few determinants of gallstone formation have been identified in cohort studies. The aim was to identify further determinants for gallstones in a Danish cohort and to perform a meta-analysis of results from existing cohorts. <b>Material and methods:</b> Data from a cohort study was used. Gallstone incidence was assessed through repeated ultrasound examinations. Body mass index (BMI), blood pressure, self-rated health, lifestyle variables, blood lipids, and use of female sex hormones were measured at the baseline examination. Statistical analyses included logistic regression. Based on a prospective protocol, a systematic review of the literature was performed identifying all articles dealing with determinants of incident gallstones. Meta-analyses of comparable determinants were performed through fixed effect models. <b>Results:</b> Participants with no gallstones at baseline and with at least one re-examination were followed-up completely (mean 11.6 years, <i>N</i> = 2848). The overall cumulative incidence of gallstones was 0.60% per year. Independent positive determinants for incident gallstones were age, female sex, non-high density lipoprotein (non-HDL) cholesterol, and gallbladder polyps. In addition, BMI was positively associated in men. The systematic review additionally identified associations for comorbidities, parity, and dietary factors. Meta-analysis confirmed the significant associations for incident gallstones and age, female sex, BMI, and non-HDL cholesterol. No significant associations were found for blood pressure, smoking, alcohol consumption, HDL cholesterol, or triglycerides in meta-analyses. <b>Conclusions:</b> Age, female sex, BMI, non-HDL cholesterol, and polyps are independent determinants for gallstone formation. Incident gallstones and the metabolic syndrome share common risk factors. More studies are needed for further exploration.

**研究目标：** 目前仅在队列研究（cohort study）中明确了少数胆结石（gallstone）形成的危险因素。本研究旨在丹麦队列中进一步筛查胆结石的潜在危险因素，并对现有队列研究的结果开展荟萃分析（meta-analysis）。
**材料与方法：** 本研究采用一项队列研究的数据。通过重复超声检查评估胆结石的发病率。基线检查时收集了受试者的体重指数（Body Mass Index, BMI）、血压、自评健康状况、生活方式变量、血脂水平以及女性性激素使用情况。统计学分析采用logistic回归（logistic regression）。基于前瞻性研究方案，本研究对文献开展系统评价（systematic review），筛选所有探讨新发胆结石危险因素的研究。针对具有可比性的危险因素，采用固定效应模型（fixed effect models）进行荟萃分析。
**研究结果：** 基线无胆结石且至少接受过一次复查的受试者被完整纳入随访（平均随访时长11.6年，*N* = 2848）。胆结石的总体年累积发病率为0.60%。新发胆结石的独立正向危险因素包括年龄、女性性别、非高密度脂蛋白（non-high density lipoprotein, non-HDL）胆固醇以及胆囊息肉（gallbladder polyps）。此外，体重指数在男性群体中呈正向关联。系统评价还发现了合并症（comorbidities）、生育胎次（parity）与饮食因素（dietary factors）的相关关联。荟萃分析证实了年龄、女性性别、体重指数以及非高密度脂蛋白胆固醇与新发胆结石的显著关联。荟萃分析未发现血压、吸烟、饮酒、高密度脂蛋白胆固醇（high density lipoprotein cholesterol, HDL cholesterol）或甘油三酯（triglycerides）与新发胆结石存在显著关联。
**结论：** 年龄、女性性别、体重指数、非高密度脂蛋白胆固醇以及胆囊息肉是胆结石形成的独立危险因素。新发胆结石与代谢综合征（metabolic syndrome）共享部分常见危险因素。未来仍需开展更多研究以进一步探索相关机制。