GBPs are one of the most common diseases worldwide. Cholesterol polyps accounted dominantly in GBP patients, and was 67.2% in our 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 because of the trauma and cost associated with unnecessary surgery. Thus, identifying the risk factors for cholesterol polyps formation is important for its prevention as well as 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] Also, 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, we recruited cholesterol polyps patients based on pathology to avoid biases from the above confounding factor, trying to specify appropriate preventive as well as intervention measures for cholesterol polyp.
Age is an independent risk factor for cholesterol polyps. Our previous studies have found that the mean age of GBP patients is 48 years. This is consistent with our findings[13, 14] While, it is worth noting that aging may be related to changes of body's metabolism, and our previous studies have found that gallbladder polyps may disappear during long-term follow-up.[3] Self-regulation of bile metabolism may affect changes in the gallbladder mucosa. At the same time, in the cholesterol polyp group, we found a higher proportion of male, which may be related to the influence of female sex hormones on the body metabolism. But more evidence is needed.
The LDL could also contribute to cholesterol gallbladder polyp formation, and this is supported by our previous meta-analysis not specifying GBP type.[13] LDL stands for liver anabolism and cholesterol transport. High LDL can promote the formation of cholesterol polyps by lowering the sensitivity of gallbladder to cholecystokinin, which subsequent decreased gallbladder contraction, cholestasis and relative deficiency of cholic acid.[15–17] These physiological changes could promote cholesterol crystallization and polyp formation. While, Wu et al[8] found that TG, TC, HDL, and LDL showed no statistical differences 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 conjecture.
Liver function status had a certain influence on the formation of cholesterol polyps. The specific mechanism of the relationship between liver function status and cholesterol polyps is unclear, and the poor liver function may be related to hypermetabolic syndrome, including obesity, hyperglycemia, hyperlipidemia and hypertension.[18] Lipid metabolism, together with abnormal liver function, may interacts closely and simultaneously contribute to the formation of cholesterol polyps. The mechanisms need to be further discussed in the future. Additionally, BMI was an independent risk factor for cholesterol polyps, which is consistent with previous research. [7] Previous studies found that the formation of GBP was closely related to overweight status of patients.[18–20] Thus, weight control may help reduce the risk of cholesterol polyps formation. We suspect that both liver function metabolism and BMI may be related to abnormal lipid metabolism, which, of course, need further studies to confirm.
This paper has several limitations. Selection bias may occur in the surgeon's decision and more samples may be needed in future studies. But no previous studies have explored the risk factors of cholesterol polyps formation on a pathologic basis, and this study was performed based on multicenter data to achieve better evaluation effect. 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 may be needed to be further studied to illustrate the specific mechanism of cholesterol polyps formation.[21]
In conclusion, this study is to analyze the risk factors of cholesterol polyps on a pathological basis. Age, LDL, AST, and BMI were independent risk factors for cholesterol polyps. Active control of risk factors affecting cholesterol polyps may reduce the incidence of cholesterol polyps, and there may be a new mechanism of cholesterol polyps in gallbladder. Lipid metabolism disorders may play an important role, which is worth further exploration in the future.