Gallbladder polyps are one of the most common diseases worldwide. Cholesterol polyps are the most common form in patients with GBP, and comprised 67.2% in this study. Few previous studies have indicated that cholesterol polyps have the potential to become malignant, and surgical removal of cholesterol polyps may not be necessary. Non-surgical treatment and prevention can bring more benefits to patients by avoiding the trauma and costs associated with unnecessary surgery. Thus, identifying the risk factors for cholesterol polyp formation is important for prevention and individualized treatment. However, previous etiological studies investigating risk factors for gallbladder polyps formation failed to separate cholesterol polyps from other types, such as inflammatory polyps and adenomatous polyps [4, 6, 8]. In addition, false-positive results are inevitable in the diagnosis of cholesterol polyps by abdominal ultrasound, a diagnostic method widely used in previous studies [11, 12]. Thus, this study recruited patients with cholesterol polyps based on pathology to avoid biases from the above confounding factor, in order to determine appropriate preventive as well as interventional measures for cholesterol polyps.
Age was an independent risk factor for the presence of cholesterol polyps. Previous studies have found that the mean age of patients with GBP is 48 years, which is consistent with the results of the study [13, 14]. However, it is worth noting that aging may be related to changes in body metabolism, and previous studies have found that gallbladder polyps may disappear during long-term follow-up . Self-regulation of bile metabolism may affect changes in the gallbladder mucosa. At the same time, in the cholesterol polyp group, a higher proportion of males, which may be related to the influence of female sex hormones on body metabolism. However, further evidence is needed.
LDL could also contribute to cholesterol gallbladder polyp formation, and this is supported by our previous meta-analysis, which did not specify the GBP type . LDL is representative of the status of liver anabolism and cholesterol transport. High LDL can promote the formation of cholesterol polyps by lowering the sensitivity of the gallbladder to cholecystokinin, which subsequently results in decreased gallbladder contraction, cholestasis, and a relative deficiency of cholic acid [15,16,17]. Meanwhile, the formation of cholesterol polyps may be related to abnormal reverse cholesterol transport related to HDL. These physiological changes can promote cholesterol crystallization and polyp formation. Wu et al.  found that TG, TC, HDL, and LDL were not statistically different between the cholesterol polyp group and the non-cholesterol polyp group, indicating that lipid levels may only play a partial role in the formation of cholesterol polyps. Thus, more potential serum indicators are needed to support our hypothesis.
Liver function status has a certain influence on the formation of cholesterol polyps. The specific mechanism of the relationship between the two is unclear, and poor liver function may be related to symptoms of hypermetabolic syndrome, including obesity, hyperglycemia, hyperlipidemia, and hypertension . Lipid metabolism, together with abnormal liver function, may interact closely and simultaneously contribute to the formation of cholesterol polyps. These mechanisms need to be further investigated. Additionally, BMI was an independent risk factor for cholesterol polyps, which is consistent with previous research . Previous studies have found that the formation of GBP is closely related to the overweight status of patients [18,19,20]. Thus, weight control may help reduce the risk of cholesterol polyp formation. However, epidemiological surveys in western countries have produced different results from this study, which may be related to the differences in diet and living habits of the population . Both liver function metabolism and BMI may be related to abnormal lipid metabolism, which, of course, requires further study.
Study strengths and limitations
This study is the first to explore the risk factors of cholesterol polyp formation from a pathological perspective, and it was performed based on multicenter data to achieve a better evaluation effect. This study had several limitations. Selection bias may occur in the surgeon’s decision, and a prospective study may be needed in the future. Although serum lipids are closely related to the formation of gallbladder cholesterol polyps and cholesterol calculus, other potential factors, such as bile acid and bile bacteria types, need to be further studied to illustrate the specific mechanism of cholesterol polyp formation .