Clinical characteristics of hospitalized patients with benign gallbladder disease: a large-scale retrospective analysis

This is a large-scale retrospective observational study included 36,298 patients with benign gallbladder disease who underwent treatment at a major gallstone center in China from January 2019 to December 2024. According to institutional records, the center treats approximately 6,000 to 8,000 patients with benign gallbladder disease annually. This data, derived from the patient admission statistics of our hospital, provides a clearer and more verifiable reflection of our center’s work in this field. We confirm the accuracy of the above data, which can be verified by contacting our organisation. All benign gallbladder disease were diagnosed according to International Classification of Diseases (ICD) codes, including gallstones (K80), gallbladder polyps (K82.802) and gallbladder adenomyosis (K82.803). This study was approved by the Medical Ethics Committee of Dongfang Hospital(No [2022] Review Document No. (107)), Tongji University, Shanghai, China. Therefore, the study was performed in accordance with with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all participants in this study (Patients under the age of 18 have obtained the informed consent of their legally responsible persons). The reporting of this cross-sectional study follows the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist, which provides recommendations for clear and comprehensive reporting of observational research. Diagnostic criteria: Gallstones, gallbladder polyps and gallbladder adenomyosis were diagnosed based on imaging examinations of the ultrasound, abdominal CT and magnetic resonance cholangiopancreatography (MRCP), combined with the patient’s clinical symptoms. The above diseases were diagnosed according to the ‘gold standard’ of pathology after surgery. Of the total study, 72% of patients (26,136 patients) received a post-operative pathological diagnosis, while the remaining 28% (10,162 patients) were diagnosed based on imaging studies, laboratory indicators, and clinical symptoms. The use of the histopathological gold standard for a majority of patients ensures the accuracy of the diagnoses, while the clinical diagnostic approach for the remaining patients was based on standard clinical practice. Inclusion criteria: (1) Gallstone diagnosed according to ICD-10 K80; (2) Gallbladder polyps diagnosed according to ICD-10 K82.802; (3) Gallbladder adenomyosis diagnosed according to ICD-10 K82.803; (4) Patients who received inpatient treatment at this center and had detailed basic demographic information. Exclusion criteria: 1,815 patients (5% of the total cohort) were excluded due to missing data on basic characteristics and discharge diagnoses. The participant flowchart is shown in Fig.  1 . Fig. 1 Flowchart Flowchart Gender, Age, Length of stay, Hypertension, DM, coronary heart disease (CHD), CBDS and Dyslipidaemia (including hypercholesterolaemia, hypertriglycerolaemia and mixed hyperlipidaemia) of all patients were collected from the electronic medical records of hospital information system (HIS), which is routinely audited and maintained to ensure accuracy and completeness of clinical records. Patients were geographically distributed according to their residential address (Northeast, Eastern, Central, North, Southern, Northwest, Southwest). Gallbladder inflammation was classified into three categories: chronic cholecystitis, acute cholecystitis and perforation of gangrenous origin. This classification is based on the Tokyo Acute Cholecystitis Severity Grading Guidelines in combination with the routine clinical assessment of cholecystitis symptoms by gallstone disease specialists. The classification reflects the severity of the disease, as severity is known to have significant implications for treatment and prognosis. Chronic cholecystitis is characterized by ongoing inflammation, while acute cholecystitis involves sudden worsening of symptoms, and perforation of gangrenous origin represents a severe and life-threatening stage of the disease. Acute cholecystitis includes the following international disease codes (K80.000, K80.002, K81.000, K81.002, K81.006); Perforation of gangrenous origin includes the following international codes (K80.001, K81.003, K82.200, K81.008, K81.005). Females are divided into menstruation and postmenopausal. Due to system limitations, it is not possible to fully obtain the patient’s true menstruation status. According to previous literature reports, females over the age of 50 are classified as post-menopausal after extensive consideration [ 46 – 48 ], However, this classification does not account for individual variations in menopause timing. Many women experience menopause before age 50, while others may continue menstruating beyond this age. Although the classification method used may introduce bias, it is the best option given the available data. Descriptive statistical analysis was performed on the collected data, summarising the central tendency and dispersion of continuous variables and the frequency and percentage of categorical variables. Comparisons between groups of categorical variables were assessed using Pearson’s chi-squared test or Fisher’s exact test. Multinomial logistic regression analysis was used to assess risk factors associated with gallbladder inflammation. The variance inflation factor (VIF) and Tolerance was used to diagnose multiple collinearity for the included independent variables. A VIF value greater than 5 or a tolerance less than 0.1 indicates high multicollinearity. In the event that high multicollinearity was detected, variables with VIFs greater than 5 or tolerance values less than 0.1 were removed from the analysis to ensure the robustness of the multinomial logistic regression model. Variables with P  < 0.05 in univariate analysis were then included in Multinomial logistic regression analysis. IBM SPSS Statistics version 27 and R version 4.3.0 were used for data analysis. A two-tailed p value of less than 0.05 was considered statistically significant.

The mean age of patients with gallstones was 50.21 ± 15.31 years, those with gallbladder polyps was 43.90 ± 13.53 years, and those with gallbladder adenomyosis was 49.36 ± 13.28 years (Table  1 ). Figure  2 (a-c) illustrates the age distribution of benign gallbladder disease. It is evident that the incidence of gallstones increases steadily after the age of 20 years, peaking between ages 30 and 45, then decreasing slightly before rising again between ages 55 and 70. After this point, the trend gradually declines; Gallbladder polyps peak between the ages of 30 and 40 years, with a gradual decline thereafter. Gallbladder adenomyosis generally peaks between the ages of 35 and 65 years, with a gradual decline after the age of 65 years. The overall gender ratio in the gallstone population was approximately 1:1.38(male: female = 13175:18304), gallbladder polyps was 1.03:1(male: female = 3198:3113) and gallbladder adenomyosis was 1:1.28(male: female = 1057:1351) (Table  1 ). Figure  3 shows the gender distribution of benign gallbladder disease. All three types of benign gallbladder disease were more prevalent in economically developed regions (Eastern China), and the proportion of gallstones with acute cholecystitis (23.9%) was higher than that of other benign gallbladder disease (Table  1 ). Table 1 Basic characteristics of benign gallbladder disease Variables Gallbladder stones N  = 31,479 Gallbladder polyps N  = 6311 Gallbladder adenomyosis N  = 2408 Age 50.21 ± 15.31 43.90 ± 13.53 49.36 ± 13.28 Gender  female 18,304(58.1%) 3113(49.3%) 1351(56.1%)  male 13,175(41.9%) 3198(50.7%) 1057(43.9%) CBDS 726(2.3%) 12(0.2%) 14(0.6%) Dyslipidemia 257(0.8%) 37(0.6%) 23(1%) Hypertension 5094(16.2%) 632(10%) 305(12.7%) DM 2052(6.5%) 203(3.2%) 101(4.2%) CHD 965(3.1%) 64(1%) 35(1.5%) Region  northeast China 486(1.5%) 120(1.9%) 45(1.9%)  eastern China 29,851(94.8%) 5933(94%) 2272(94.4%)  central China 376(1.2%) 91(1.4%) 24(1%)  north China 212(0.7%) 55(0.9%) 24(1%)  southern China 64(0.2%) 20(0.3%) 8(0.3%)  northwest China 161(0.5%) 25(0.4%) 8(0.3%)  southwest China 201(0.6%) 35(0.6%) 14(0.6%) Inflammatory state of the gallbladder  chronic inflammation 22,906(72.8%) 5890(93.3%) 2255(93.6%)  acute cholecystitis 7532(23.9%) 413(6.5%) 148(6.1%)  perforation of gangrenous origin 1041(3.3%) 8(0.1%) 5(0.2%)  Duration of hospitalisation 2(2,4) 2(2,3) 2(2,3) CBDS common bile duct stones, DM diabetes mellitus, CHD coronary heart disease Basic characteristics of benign gallbladder disease CBDS common bile duct stones, DM diabetes mellitus, CHD coronary heart disease Fig. 2 Age distribution characteristics of benign gallbladder disease Age distribution characteristics of benign gallbladder disease Fig. 3 Gender distribution characteristics of benign gallbladder disease Gender distribution characteristics of benign gallbladder disease The distribution of benign gallbladder disease is shown in Fig.  4 , including 28,140 (77.52%) with gallstones only, 3784(10.42%) with gallbladder polyps, and 684(1.88%) with gallbladder adenomyosis; 1966(5.42%) with both gallstones and gallbladder polyps, gallstones and gallbladder adenomyosis 1163(3.2%), gallbladder polyps and gallbladder adenomyosis 351(0.97%); 210(0.58%) had all three of the above-mentioned benign gallbladder disease simultaneously. Fig. 4 Characteristics of the intersection between gallbladder stones, gallbladder polyps and gallbladder adenomyosis Characteristics of the intersection between gallbladder stones, gallbladder polyps and gallbladder adenomyosis In the female subgroup, the risk of benign gallbladder disease associated with menstruation was analysed. The risk of gallstones in menstruation women was significantly lower than in postmenopausal women(85.28% vs. 90.26%, OR: 0.625, 95%CI: 0.575–0.680, p  < 0.0001); The risk of gallbladder polyps was higher in postmenopausal women(17.66% vs. 12.12%, OR: 1.555, 95%CI: 1.439–1.680, p   0.05) (Fig.  5 ). Fig. 5 Menstruation and the risk associated with the development of benign gallbladder disease in women. Note: ( a ) Gallbladder stones; ( b ) Gallbladder polyps; ( c ) Gallbladder adenomyosis Menstruation and the risk associated with the development of benign gallbladder disease in women. Note: ( a ) Gallbladder stones; ( b ) Gallbladder polyps; ( c ) Gallbladder adenomyosis The independent variables of age, gender, gallbladder stones, gallbladder polyps, gallbladder adenomyosis, CBDS, dyslipidemia, hypertension, DM and CHD were included in a linear regression model for multicollinearity diagnosis. The results indicate that the VIF values were all less than 5 and the tolerance values were all much greater than 0.1, so multicollinearity between the independent variables was ruled out(Table  2 ). Multinomial logistic regression analysis was conducted with the chronic cholecystitis in the gallbladder as the reference category. The results showed that age, gender, gallbladder stones, gallbladder polyps, gallbladder adenomyosis, CBDS, hypertension, DM, and CHD were significantly associated with the inflammatory state of the gallbladder (all p   30 years had an increased risk. The risk of acute cholecystitis was higher in individuals aged 45–60 years(OR: 1.848; 95% CI: 1.618–2.114, p  < 0.001), while the risk of perforation of gangrenous origin was higher in individuals aged 30–45 years(OR: 3.165; 95% CI: 2.242–4.464, p  < 0.001); Male had a higher risk of acute cholecystitis(OR: 1.333; 95% CI: 1.265–1.406, p  < 0.001) and perforation of gangrenous origin(OR: 2.196; 95% CI: 1.934–2.494, p  < 0.001) than female; Gallstones were associated with a higher risk of acute cholecystitis(OR: 2.857; 95% CI: 2.370–3.436, p  < 0.001); Gallbladder polyps and gallbladder adenomyosis were associated with a lower risk of acute cholecystitis or perforation of gangrenous origin(both p  < 0.001); CBDS were associated with a higher risk of acute cholecystitis(OR: 2.024; 95% CI: 1.727–2.370, p  < 0.001) and perforation of gangrenous origin(OR: 2.481; 95% CI: 1.848–3.333, p  < 0.001);DM was associated with a higher risk of acute cholecystitis(OR: 1.316; 95% CI: 1.183–1.462, p  < 0.001) and perforation of gangrenous origin(OR: 1.773; 95% CI: 1.425–2.208, p  < 0.001); Hypertension was associated with a higher risk of acute cholecystitis(OR: 1.304; 95%CI: 1.209–1.406, P  < 0.001); CHD was associated with a higher risk of acute cholecystitis(OR: 1.328; 95%CI: 1.149–1.534, P   30,≦ 45 0.380 2.629 > 45,≦ 60 0.384 2.605 > 60,≦ 75 0.385 2.600 > 75 0.707 1.415 Gender 0.986 1.014 Gallbladder polyps 0.478 2.090 Gallbladder adenomyosis 0.910 1.099 Gallbladder stones 0.457 2.190 Common bile duct stones 0.985 1.015 Dyslipidemia 0.989 1.011 Hypertension 0.775 1.290 DM(Diabetes Mellitus) 0.854 1.171 CHD(Coronary heart disease) 0.891 1.122 Dependent Variable: inflammatory state of the gallbladder Multicollinearity diagnosis Dependent Variable: inflammatory state of the gallbladder Dependent Variable: inflammatory state of the gallbladder Table 3 Multinomial-logistic regression analysis of factors to inflammatory state of the gallbladder Variables Acute cholecystitis Perforation of gangrenous origin Coefficient SE OR(95%Cl) p Coefficient SE OR(95%Cl) p Age  ≦ 30 Ref Ref  > 30,≦ 45 0.598 0.077 1.818(1.563–2.119) < 0.001 1.151 0.176 3.165(2.242–4.464)  45,≦ 60 0.615 0.069 1.848(1.618–2.114) < 0.001 0.797 0.138 2.217(1.695–2.907)  60,≦ 75 0.530 0.067 1.698(1.488–1.938) < 0.001 0.982 0.137 2.667(2.041–3.497)  75 0.360 0.066 1.435(1.259–1.631) < 0.001 0.555 0.130 1.742(1.351–2.247) < 0.001 Gender  Female Ref Ref  Male 0.288 0.027 1.333(1.265–1.406) < 0.001 0.787 0.065 2.196(1.934–2.494) < 0.001 Gallbladder polyps  No Ref Ref  Yes -0.935 0.067 0.392(0.344–0.448) < 0.001 -2.463 0.356 0.085(0.042–0.171) < 0.001 Gallbladder adenomyosis  No Ref Ref  Yes -1.190 0.089 0.304(0.256–0.362) < 0.001 -2.355 0.450 0.095(0.039–0.229) < 0.001 Gallbladder stones  No Ref Ref  Yes 1.048 0.095 2.857(2.370–3.436) < 0.001 - - - - Common bile duct stones  No Ref Ref  Yes 0.705 0.081 2.024(1.727–2.370) < 0.001 0.909 0.150 2.481(1.848–3.333) < 0.001 Dyslipidemia  No Ref Ref  Yes 0.214 0.137 1.238(0.946–1.621) 0.119 0.081 0.333 1.085(0.564–2.083) 0.922 Hypertension  No Ref Ref  Yes 0.266 0.039 1.304(1.209–1.406) < 0.001 0.030 0.092 1.031(0.861–1.233) 0.742 Diabetes Mellitus  No Ref Ref  Yes 0.274 0.054 1.316(1.183–1.462) < 0.001 0.572 0.112 1.773(1.425–2.208) < 0.001 Coronary heart disease  No Ref Ref  Yes 0.284 0.073 1.328(1.149–1.534) < 0.001 -0.030 0.167 0.970(0.700-1.344) 0.856 Reference category : chronic cholecystitis Multinomial-logistic regression analysis of factors to inflammatory state of the gallbladder Reference category : chronic cholecystitis

Benign gallbladder disease is among the most common digestive disorders worldwide [ 1 – 3 ], especially in developed and developing countries, and impose a significant economic burden on society. It is reported that about 20 million to 25 million adults in the United States have gallstones, and the annual medical burden directly or indirectly caused by gallstones is about 6.2 billion US dollars [ 4 – 6 ]. In the UK, the financial burden of gallstones on the NHS exceeded 200 million pounds in the 2018/19 [ 7 ]. Benign gallbladder disease mainly include gallstones, gallbladder polyps and gallbladder adenomyosis. The global prevalence of gallstones is estimated to range from 6–25% [ 7 – 11 ], that of gallbladder polyps from 0.3–9.5% [ 12 – 16 ], and that of gallbladder adenomyosis from 2–9% [ 16 – 19 ]. The prevalence of gallstones is higher in women, with a male-to-female ratio of approximately 1:1-3.92 [ 4 , 20 , 21 ]. This difference is mainly related to ethnic factors; gallbladder adenomyosis manifests more frequently in women [ 19 , 22 , 23 ]; and gallbladder polyps are more prevalent in men [ 13 , 24 , 25 ] (male: female = 1.15–1.7:1). The prevalence of gallstones increases significantly after the age of 40, especially in women [ 4 , 8 , 26 , 27 ]. As individuals age, symptoms often become more subtle, and treatment is often complicated by serious complications, making surgery significantly more difficult. Gallbladder polyps are predominantly observed in individuals between the ages of 40 and 59 years [ 24 , 25 , 28 – 30 ], but their incidence of clinical symptoms is low, and their potential cancer risk cannot be ignored. Gallbladder adenomyosis, like gallbladder polyps, has a low incidence of symptoms, and its cancer risk is mainly related to classification. Segmental adenomyosis has a higher cancer risk, especially in elderly patients [ 31 ] . Risk factors for gallstone formation can be classified into congenital and acquired factors [ 4 , 8 , 11 , 32 – 40 ]. Congenital factors include female, advancing age, family history and race. Acquired factors include blood Se, diet, rapid weight loss, obesity, physical activity, drugs and total parenteral nutrition. For example, dyslipidemia, diabetes, metabolic syndrome, and some chronic diseases (such as hemolytic diseases, chronic liver disease, and Crohn’s disease) are a combination of congenital and acquired factors. The primary risk factors for gallbladder polyps include male, dyslipidemia, HBsAg positivity and age, especially middle age [ 13 , 14 , 24 , 25 ]. Gallbladder adenomyosis is closely related to gallbladder stones, chronic inflammation of the gallbladder and increased intra-luminal pressure [ 18 , 31 , 41 – 43 ]. As can be seen from the above epidemiological characteristics, the risk factors associated with benign gallbladder disease involve many aspects of life. The combined effect of these factors makes it the most common digestive disease with the highest incidence and medical burden. This prompts the question of the treatment concept for benign gallbladder disease, which is mainly based on the concepts of cholecystectomy and conservative treatment with subsequent follow-up observation. With the advent of minimally invasive surgery, innovations in endoscopic technology have promoted the popularisation of laparoscopic cholecystectomy. At the same time, some scholars have proposed laparoscopic cholecystotomy and stone removal and other surgical methods that preserve the function of the gallbladder based on the concept of precision medicine [ 44 ], which has also greatly increased the number of surgeries for benign gallbladder disease. The primary risks that increase the difficulty of laparoscopic cholecystectomy are the inflammatory. These factors can significantly prolong the patients’ hospital stays of the gallbladder and anatomical abnormalities. The most serious adverse event is bile duct injury [ 45 ]. In particular, the incidence of gallbladder inflammation is significantly higher than that of anatomical abnormalities. Gallbladder inflammation causes oedema and dense adhesion of the surrounding tissues of the gallbladder, and the anatomical landmarks in the gallbladder triangle cannot be identified, which easily causes bile duct injury. These factors can significantly prolong the patient’s hospital stay and increase hospital costs. It is important to note that these epidemiological characteristics are primarily derived from data collected after patients have undergone inpatient treatment, which differs from the epidemiological surveys conducted on large-scale health examination populations. Therefore, the primary objective of this study is to analyze the clinical characteristics of hospitalized patients with benign gallbladder disease based on a large dataset, and compare these findings with those from the physical examination population in existing literature.

This study represents one of the largest clinical studies of hospitalized patients with benign gallbladder disease. Unlike previous studies based on large-scale physical examination populations, this study found that among inpatients with benign gallbladder disease, the proportion of those with gallstones was as high as 86.72%, gallbladder polyps 17.39%, and gallbladder adenomyosis 5.66%. The main reason is that the mobility of gallstones within the gallbladder, with the contraction of the gallbladder and changes in body position, the stones can easily become lodged in the neck of the gallbladder or the cystic duct, which in turn can trigger typical clinical symptoms, or damage gallbladder function through chronic inflammation and irritation over the long term, leading to nonspecific manifestations. Therefore, compared to gallbladder polyps and gallbladder adenomyosis, which have a lower incidence of clinical symptoms, gallstone disease requires hospitalization in significantly more patients. This study found that the incidence of gallstones combined with gallbladder polyps was 6%, which is similar to the 0.25%-6.5% reported in the literature [ 14 , 24 , 25 ], and also describes the overlapping characteristics of these three diseases. Further analysis revealed that the prevalence of gallstones showed two peaks in the age distribution, one between 30 and 45 years and another between 55 and 70 years, followed by a gradual decline. This may be due to the fact that as people get older, their perception of symptoms decreases and they become less sensitive to symptoms. The proportion of patients requiring inpatient treatment begins to decrease. However, it should be noted that while symptoms can be subtle, when they occur, they often result in more serious complications. However, alternative explanations must also be considered. Competing mortality could contribute to the observed decline in older individuals, as those with severe disease may not survive long enough to present for treatment. Additionally, lower surgical candidacy in older populations due to comorbidities may result in fewer older patients seeking or undergoing surgery, thereby contributing to the observed decrease in the number of diagnoses in this group. In contrast to this study and previous research, a study that included 438 cases of gallbladder polyps and followed them up for 6 years found that the incidence of gallbladder polyps was higher in middle-aged women [ 29 ] (female: male = 1.44:1), which may be due to differences in sample size. Overall, the age and gender distribution characteristics of gallstones, gallbladder polyps and gallbladder adenomyosis are similar to previous studies [ 4 , 8 , 13 , 19 – 30 ]. The geographic distribution shows that 94.8% of patients came from Eastern China, The high concentration of patients from eastern China may limit the generalizability of our findings, particularly to regions with differing medical resources and socioeconomic conditions. Eastern China, especially urban areas like Shanghai, has advanced healthcare infrastructure, including specialized institutions, modern diagnostic tools, and experienced medical staff. As a result, patients with more severe symptoms are more likely to seek treatment at our hospital. In contrast, patients from rural areas may face challenges such as limited access to healthcare, delayed diagnosis, and referral difficulties. These regional differences may impact the types and severity of gallbladder diseases treated at our institution, introducing potential bias. While our study provides valuable insights into the clinical characteristics of benign gallbladder disease in an urban setting, these findings may not fully apply to populations in less developed areas. We recommend that future studies include multi-center data from diverse regions to provide a more comprehensive understanding of benign gallbladder disease across China, accounting for variations in healthcare access, socioeconomic factors, and referral patterns. It is well known that women are one of the main risk factors for gallstones, which is closely related to their sex hormone levels, number of births, use of oral contraceptives, and estrogen replacement therapy [ 4 , 49 , 50 ]. During pregnancy in particular, 5% to 30% of women will develop microstones or sludge in the gallbladder [ 51 , 52 ], but most of these will gradually disappear after pregnancy. This gender gap gradually narrows after menopause. Further research found that the risk of gallstones in menstruation women was 0.625 times that of postmenopausal women (95% CI: 0.575–0.680). These results differ significantly from those of other studies [ 40 , 53 ]. In this study, postmenopausal women did not receive estrogen replacement therapy, but the incidence of gallstones was 1.6 times that of menstruating women. There are two possible reasons for this phenomenon: First, the significant decline in estrogen levels in postmenopausal women leads to abnormal lipid metabolis, which in turn causes abnormalities in the bile microenvironment in the gallbladder, bile stasis, and cholesterol supersaturation [ 54 , 55 ]. Second, as individuals age, the contractile function of the gallbladder naturally declines. However, the association between menstrual status and the risk of gallbladder disease should be interpreted with caution. Classifying postmenopausal women based on the arbitrary age threshold of 50 years may lead to misclassification. We acknowledge that the lack of detailed menstrual status data may weaken the validity of our conclusions regarding the role of menstrual status in the risk of gallbladder disease. Further research using accurate, personalised menstrual status data is needed to better understand this relationship.This study focused on the inflammatory state of the gallbladder and performed a multinomial logistic regression analysis, and found that age, male, gallstones, CBDS, hypertension, CHD and DM were significantly associated with the inflammatory state of the gallbladder. Compared to chronic cholecystitis, individuals aged 45–60 years have a 1.848 times higher risk of developing acute cholecystitis (OR: 1.848; 95% CI: 1.618–2.114). Clinically, this suggests that middle-aged patients are more prone to severe forms of gallbladder inflammation, likely due to a combination of aging and the accumulation of risk factors such as chronic diseases. This finding highlights the need for early intervention and monitoring for patients in this age group to prevent the progression to more severe stages of gallbladder disease. Additionally, patients with gallbladder stones are 2.857 times more likely to develop acute cholecystitis than those without gallbladder stones (OR: 2.857; 95% CI: 2.370–3.436), patients with CBDS are 2.024 times more likely to develop acute cholecystitis than those without CBDS (OR: 2.024; 95%CI: 1.727–2.370). CHD, DM and Hypertension were associated with a higher risk of acute cholecystitis. Compared with chronic cholecystitis, the risk of gallbladder perforation of gangrenous origin is 3.165 times higher in patients aged 30–45 years (OR: 3.165; 95% CI: 2.242–4.464) than in those under 30. Male have a 2.196 times higher risk of gallbladder perforation of gangrenous origin compared to female (OR: 2.196; 95% CI: 1.934–2.494). Additionally, acute cholecystitis in males was 1.333 (OR: 1.333; 95% CI: 1.265–1.406), this indicates that male are more prone to severe complications than female. This finding is particularly important in clinical practice, where gender-specific prevention strategies and treatment plans should be considered. CBDS is associated with a 2.481 times higher risk of gallbladder perforation of gangrenous origin compared to the absence of CBDS (OR: 2.481; 95% CI: 1.848–3.333).DM (OR: 1.773; 95% CI: 1.425–2.208) has associated with a higher risk of gallbladder perforation of gangrenous origin [ 56 ]. Gallstones significantly increase the risk of both acute cholecystitis and perforation of gangrenous origin, highlighting their key role as a major driver of gallbladder inflammation. Clinically, gallstones may become lodged in the gallbladder neck due to their mobility, leading to bile stasis. This stagnation creates an ideal environment for bacterial infection, resulting in inflammation of the gallbladder. Furthermore, gallstones can migrate into the common bile duct, causing CBDS, which leads to biliary obstruction and can worsen gallbladder inflammation, and if untreated, it can progress to sepsis, posing a significant threat to the patients’ health. Therefore, early diagnosis and timely management of gallstones—particularly in patients presenting with symptoms such as abdominal pain, fever, and nausea—are critical. In cases where symptoms persist or complications arise, cholecystectomy should be prioritized to prevent gangrenous perforation and other life-threatening conditions. For CBDS, the use of endoscopic retrograde cholangiopancreatography (ERCP) or surgical management for stone removal should be considered promptly to alleviate biliary obstruction and prevent the progression of inflammation. DM is another significant risk factor, as it was found to increase the likelihood of both acute cholecystitis and perforation of gangrenous origin. DM patients are more prone to gallstone formation due to metabolic abnormalities, which increases the formation of gallstones. Moreover, DM can exacerbate gallbladder inflammation by impairing the immune response, making it harder for the body to control infection and inflammation. Therefore, clinicians should consider optimizing glucose control as part of the preventive strategy for DM patients, particularly those at higher risk for gallstone formation and gallbladder inflammation. Furthermore, routine screening for gallstones and early intervention may help DM patients avoid severe complications, such as acute cholecystitis or perforation. Meanwhile, this study found that gallbladder polyps and adenomyosis appeared to be protective against severe inflammation. However, we recognize the potential for detection bias in these findings. Both gallbladder polyps and adenomyosis are often incidental findings discovered during imaging performed for unrelated reasons. As a result, individuals with these conditions may be less likely to present with more severe symptoms or complications that would necessitate hospitalization or surgery. Consequently, the association between these conditions and reduced severity of inflammation may reflect an underreporting of more severe cases in patients with polyps or adenomyosis rather than a true protective effect. Further studies with prospective designs and more detailed clinical data would be required to confirm whether this apparent protective effect is real or merely a result of detection bias.When managing patients with benign gallbladder disease, special attention should be given to the above-mentioned characteristic populations, and careful examinations should be performed. During surgery, the aim should be to remove the lesion as much as possible, rather than completely resecting the gallbladder radically, in order to minimise the difficulty of the operation and avoid bile duct injury. Based on the concept of precision medicine in modern medicine, individualized treatment combined with prevention can better achieve precision treatment and avoid wasting medical resources. A large-scale data study of inpatients with benign gallbladder disease has the potential to contribute to two key areas of research. Firstly, it can provide valuable epidemiological information on the population of inpatients [ 57 ]. Secondly, it can further refine clinical management strategies for the disease. Benign gallbladder disease is one of the most economically burdensome diseases in the digestive system [ 3 ]. It has a high incidence rate and there are also differences in treatment concepts. In clinical practice, some patients frequently visit the doctor for different opinions provided by different doctors. This can cause significant anxiety for patients and also result in a considerable waste of medical resources. The root cause is that doctors differ in their judgments as to whether intervention is necessary. By conducting a large data survey of inpatients with benign gallbladder disease, high-risk patients can be identified early, so that early diagnosis and treatment can be achieved, the occurrence of complications can be reduced, and bile duct damage caused by increased surgical difficulty due to delayed treatment can be avoided [ 57 ]. This study has several limitations that should be considered when interpreting the findings. A major limitation is the lack of precise menstrual status data. Due to system limitations, postmenopausal women were classified based on an age cutoff of 50 years. However, this approach does not account for individual variations in the timing of menopause. Many women experience menopause before the age of 50, while others may continue menstruating beyond this age. The absence of detailed menstrual history data introduces the possibility of misclassification, which may weaken the validity of the findings regarding the association between menstrual status and gallbladder disease risk. Future studies with more accurate and personalized menstrual status data would be crucial to refine this analysis. Moreover, several other important variables were not fully addressed in this study. These include parity (number of births), dietary factors, and hormone therapy use, which are known to influence gallbladder disease risk, especially in women. Parity is particularly relevant as it has been shown to affect gallbladder function, while dietary factors and hormone therapy (including estrogen replacement therapy) are critical contributors to gallstone formation. Unfortunately, these variables were not available in our dataset. The lack of these data introduces potential biases and limits our ability to draw comprehensive conclusions about all the factors influencing gallbladder disease. In addition to these factors, the study also faced challenges in obtaining comprehensive medical data for many patients. Details such as body mass index, clinical manifestations, blood lipid levels, liver function, and inflammatory indicators were not fully obtained. As a result, comparisons with local health examination populations from the same period could not be made, and the study could only be compared to previous large-scale epidemiological studies of benign gallbladder disease. The absence of these key variables may introduce confounding, affecting the interpretation of our findings. While electronic medical records (EMRs) provide valuable data, miscoding in EMRs is a potential source of error, particularly regarding diagnostic and procedural data. These inaccuracies may influence the reliability of the results and limit the generalizability of the study. Furthermore, this cohort consists exclusively of patients from a specialized referral center, which could introduce referral bias, as patients in such centers may present with more severe or symptomatic cases compared to the general population. Finally, the results of this study are primarily applicable to hospitalized patients with benign gallbladder disease who present with prominent symptoms or severe disease. As this study is based exclusively on hospitalized patients from a single tertiary gallbladder center, the findings may not be generalizable to the broader population, including individuals with asymptomatic or less severe disease who do not require hospitalization. This potential selection bias should be considered when interpreting the associations observed in this study. We recommend that future studies incorporate multi-center data or studies based on community-level or population-level data to validate the applicability of these findings across diverse patient populations and healthcare settings.

In summary, gallstones are the main cause of hospitalization for benign gallbladder disease, and the risk is higher in postmenopausal women. Middle age, male, gallstones, CBDS and DM are risk factors for inflammatory reactions in the gallbladder. Although the study results suggest that gallbladder polyps and adenomyosis share characteristics with the general population, population-based studies of hospitalized patients differ from screening populations, as they typically include more severe or symptomatic cases, which may not fully represent the broader unscreened population.