AIM: To investigate the prevalence and risk factors of polypoid lesions of gallbladder (PLG) among the health examinees in the Shanghai region, China.

METHODS: A total of 11 816 subjects who underwent health examinations in our hospital between August 2010 and February 2011 were analyzed retrospectively. Among them, there were 7174 men and 4642 women. PLG was diagnosed by the real-time ultrasonography. Those with the body mass index (BMI) ≥ 28 were considered to be obese. Blood biochemical indices were detected with the fully automatic biochemical analyzer and hepatitis B surface antigen (HBsAg) was tested by the automated enzyme immunoassay. The correlations between the prevalence of PLG and age, sex, BMI, serum cholesterol (T-Cho), triglycerides (TG), blood sugar, HBsAg, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), gallstone and fatty liver were investigated. After univariate analysis of 11 variables, stepwise logistic regression analysis was performed to explore the risk factors of PLG.

RESULTS: There was a significant difference in sex, T-Cho, HBsAg, HDL-C, LDL-C and fatty liver between the PLG-positive group and the PLG-negative group (332/163 vs 6842/4479, P = 0.003; 22/473 vs 295/11 026, P =0.013; 92/403 vs 993/10 328, P = 0.001; 47/448 vs 332/10 989, P = 0.001; 32/463 vs 381/10 940, P = 0.001; 83/412 vs 3260/8061, P = 0.001). No significant difference was found in the age, BMI, TG, blood sugar and gallstone between the two groups (47.3 ± 26 vs 45.1 ± 33, P = 0.173; 59/436 vs 1097/10 224, P = 0.102; 52/443 vs 982/10 339, P = 0.158; 17/478 vs 295/11 026, P = 0.26; 24/471 vs 395/10 926, P = 0.109). Logistic regression analysis showed that the sex, HBsAg and HDL-C were independent risk factors for the development of PLG in a descending order of HDL-C > HBsAg > sex.

CONCLUSION: In healthy people, the male gender, positive HBsAg, and low HDL-C confer higher risks of PLG development.

The prevalence of polypoid lesions of gallbladder (PLG), a common clinical gallbladder disease, is about 3%, with an increasing trend[1,2]. PLG is the general term of the limited abnormal accumulations of mucous membrane tissue of the gallbladder or the limited lesion projecting into the lumen of the gallbladder. Clinically, the types of polypoid growth of the gallbladder mainly includes cholesterol polypoid/cholesterosis, inflammatory polyp, cholesterosis with fibrous dysplasia of gallbladder, adenomyomatosis, hyperplastic cholecystosis and adenocarcinoma. Ultrasonography (US) is a convenient and non-traumatic modality used to profile the gallbladder and the position of the lesion. The application of US has improved significantly the detection rate of PLG. It is of great clinical significance to analyze the risk factors of PLG in an attempt to improve its prevention and diagnosis. This study retrospectively analyzed the prevalence and risk factors of PLG among 11 816 health examinees in our clinical center. Through the univariate and multivariate analyses, this study aimed to provide the first-hand evidences for the primary prevention of PLG.

PLG, which is often neglected due to lack of significant clinical signs or symptoms, is a common disease found in the ultrasound examinations. In recent years, with changes of diet, acceleration of the pace of life, increasing health awareness and the popularity of ultrasonography, the detection rate of PLG tends to increase, and nearly 85% of PLG are detected in a routine physical examination. It is reported that the prevalence of PLG in the Western society is 1.0%-6.9%[4-6], which is significantly lower than in the Asians. Park et al[7] reported that PLG prevalence in the South Korea was about 6.1%. Lin et al[8] reported a prevalence of 9.5% in Taiwan. After the logistic regression analysis of 34 669 cases, Lin et al[8] showed that the male gender was an independent risk factor of PLG. The domestic studies showed a prevalence of 3% in healthy adults in our country[1,2]. The Logistic regression analysis in this study showed that the gender was an independent risk factor for PLG and males bear a significantly higher risk of PLG than females. The risk of PLG in men was 1.843 times higher than in women.

In China, hepatitis B virus carriers account for 7.2% of the population. HBsAg infection may lead to acute or chronic hepatitis. In acute hepatitis, gallbladder wall thickening, volume change and abnormal bile composition can occur and the normal systolic and diastolic functions may be disrupted[9]. Cholesterol polyp is the most common type among PLGs. Compared with non-hepatitis B patients, chronic hepatitis B patients are prone to PLG and the possible causes include: (1) Liver cell cholesterol metabolic disorders may lead to the alteration of the bile composition and quantity, and increased cholesterol in the bile of the gallbladder may easily crystallize and precipitate on the gallbladder wall, resulting in abnormal deposition; (2) Hepatitis B virus activates the immune system to produce autoimmune inflammation, leading to an increased activity of the gallbladder macrophages for cholesterol phagocytosis; (3) Gastrointestinal hormone secretion and metabolic disorder may cause tension adjustment disorder of the sphincter of Oddi, causing increased bile viscosity and poor drainage; and (4) Damages of the liver Kupffer cells may compromise the detoxification of microbial toxins and phagocytic functions. Together with the small bile ducts and capillary damage, microorganisms and toxins can invade the gallbladder[10]. Our data showed that compared with PLG-negative group, PLG-positive group had a significantly higher incidence of hepatitis B virus infection. The logistic regression analysis showed that positive HBsAg was a risk factor for PLG. Lin et al[8] also reported that positive HBsAg was an independent risk factor for PLG. But there are some contrary reports[11]. The inconsistent findings may be related to the number of cases, sex ratio, ethnic differences and other factors. The role of hepatitis B virus in PLG still deserves further studies.

PLG formation mechanisms are very complicated, involving many interacting factors. The mechanisms for cholesterol polyps, the main type of PLG, have been most frequently reported. It has been reported that cholesterol polyps are related to the metabolism of cholesterol in bile. Khairy et al[12] found that in 74 patients with cholesterol polyps, 63 (85.1%) patients had elevated plasma cholesterol levels. However, other studies showed that higher plasma T-Cho and TG levels and the incidence of PLG were not necessarily correlated with PLG[13,14]. Ivanchenkova et al[15] and Zák et al[16] found that plasma HDL-C levels in patients with cholesterol polyps were significantly lower than in the control group, while LDL-C levels were significantly increased. Our data showed that compared with PLG-negative group, T-Cho and LDL-C levels were significantly higher in PLG-positive group while HDL-C levels were significantly lower. The TG level showed no significant difference between the two groups. Consistent with the report by Cantürk et al[17], our study showed that low HDL-C level was a risk factor for PLG. Currently, whether the cholesterol deposited in the gallbladder is from the plasma and the relevance between plasma TG level and PLG still remain unclear. Most studies have focused on the mechanisms of absorption and excretion of cholesterol by the mucosa of the gallbladder[18].

Although PLG is an independent disease, it is closely related to the occurrence of the gallbladder stone, which is commonly seen in PLG patients. Studies showed that PLG was often accompanied with stones, and Ito et al[19] reported that the rate of PLG with stones was 12%. Colecchia et al[20] believed that metabolic disorders of cholesterol existed in both PLG and gallbladder stones, which shared the common pathogenesis. However, these two diseases were not necessarily correlated. Our study showed that the incidence of the gallbladder stone was not significantly different between PLG-positive and PLG-negative groups.

In recent years, the prevalence of diabetes, fatty liver and obesity has been increasing year by year, affecting more and more people at younger ages. These three morbidities all belong to metabolic disorders and their roles in PLG are not consistent among previous reports[11,21,22]. Our study demonstrated that the incidences of fatty liver were not statistically different between PLG-positive and PLG-negative groups, nor the plasma glucose and obesity. The logistic regression analysis showed that diabetes, fatty liver and obesity were not risk factors of PLG.

The exact mechanisms underlying PLG pathogenesis are still not clear. This retrospective analysis has demonstrated that low HDL-C level, male gender and positive HBsAg are the risk factors for PLG, and these findings will provide the related evidence and guidance for health education, and prevention and treatment of PLG.