Who should perform pediatric laparoscopic cholecystectomies? A systematic review of the literature.

Laparoscopic cholecystectomy (LC) is an increasingly common operation in the pediatric population, although numbers remain significantly lower than in adults. Currently, this operation is performed by both adult and pediatric surgeons and there is no consensus as to whether specialist low-volume or adult high-volume surgeons should be performing this operation. A literature search was performed to compare the outcomes following pediatric LC when performed by adult or pediatric surgeons. 19,993 patients were included in this analysis. Overall, post-operative complications were reduced when LC was performed by high-volume adult surgeons, along with reduced length of stay and associated cost. Overall morbidity following LC in children is comparable to adults. When performed by higher volume adult surgeons, there was a statically significant reduction in post-operative complications and re-admission rates. Morbidity was also reduced in patients with simple cholelithiasis. Initial results show that in pediatric patients presenting with cholelithiasis, LC performed by a high-volume adult general surgeon is safer. In more complex children with needs from other specialist pediatricians, surgery performed by a pediatric surgeon is recommended. Further research with direct comparisons is still required.

[Food consumption patterns and risk of gallstone disease (GD): Case and Control Study in Rosario Argentina.] / Patrones de consumo alimentario y riesgo de enfermedad colelitiásica (EC): Estudio de Casos y Controles en Rosario Argentina.

Introduction: Nutritional exposure is considered the main environmental influence that contributes to gallstone disease (GD). Aim: The aim of this study was to determine food intakes patters and estimate risk of GD. Methods: A nested case-control study was carried out within the framework of a previous screening study conducted on a representative sample in Rosario, Argentina. Participants underwent a personal interview. Average amount of each food intake and quantity nutrients were estimated applying a food-frequency questionnaire. Food consumption patterns were identified by principal component analysis, and logistic regression analysis was used to estimate risks. Results: The sample was conformed by 51 cases and 69 controls. Two dietary patterns were identified. Cases were characterised by the unhealthy intake pattern (high intakes of animal fats, sugar, cereals, grains, cold cuts, processed meats, chicken with skin, fat beef and low intake of red vegetables and yellows, cabbages, fruits and fish). Conclusion: Controls were characterised by the healthy intake pattern (high intake of skinless chicken, nuts, lean beef, vitamin A and C rich fruits, and low consumption of chicken with skin, green leaves vegetables and sprouts). The unhealthy pattern showed an increased risk of developing GD while healthy patter behaved as a protective factor.

Introducción: La exposición nutricional se considera la principal exposición ambiental que contribuye a la formación de cálculos biliares. Objetivo: El objetivo de este trabajo fue determinar el patrón de consumo alimentario de casos y controles de EC y estimar el riesgo de desarrollar la enfermedad según los distintos patrones constituidos. Métodos: Se llevó a cabo un estudio analítico retrospectivo transversal de casos y controles, anidado a un estudio de prevalencia realizado en Rosario. Todos los participantes fueron entrevistados personalmente. El consumo de alimentos se consignó a través de un cuestionario semi-cuantitativo de frecuencia de consumo. Para determinar patrones de consumo alimentario se realizó un análisis de componentes principales, y análisis de regresión logística múltiple para evaluar riesgos. Resultados: La muestra quedó conformada por 51 casos y 69 controles. Se determinaron dos componentes que permitían diferenciar los casos de los controles, a través de las cuales se establecieron 2 patrones de consumo. Los casos se caracterizaron por un consumo determinado por el Patrón Poco saludable (altas ingestas de grasas animales, azúcar, cereales, granos, fiambres y embutidos) y los controles por el consumo del patrón Saludable (altas ingestas de pollo sin piel, frutas secas, carne vacuna magra, frutas, lácteos enteros). El patrón Poco saludable, aumentó el riesgo de desarrollar EC mientras que el patrón Saludable, se comportó como protector. Conclusión principal: Los patrones constituidos diferencian los casos de los controles, y la ingesta propia de los casos se correlaciona con un perfil de consumo que caracteriza a las culturas occidentales modernas y urbanas.

Presence and significance of telocytes in cholelithiasis and biliary dilatation in benign biliary disorders.

Telocytes are closely associated with the regulation of tissue smooth muscle dynamics in digestive system disorders. They are widely distributed in the biliary system and exert their influence on biliary motility through mechanisms such as the regulation of CCK and their electrophysiological effects on smooth muscle cells. To investigate the relationship between telocytes and benign biliary diseases,such as gallbladder stone disease and biliary dilation syndrome, we conducted histopathological analysis on tissues affected by these conditions. Additionally, we performed immunohistochemistry and immunofluorescence double staining experiments for telocytes. The results indicate that the quantity of telocytes in the gallbladder and bile duct is significantly lower in pathological conditions compared to the control group. This reveals a close association between the decrease in telocyte quantity and impaired gallbladder motility and biliary fibrosis. Furthermore, further investigations have shown a correlation between telocytes in cholesterol gallstones and cholecystokinin-A receptor (CCK-AR), suggesting that elevated cholesterol levels may impair telocytes, leading to a reduction in the quantity of CCK-AR and ultimately resulting in impaired gallbladder motility.Therefore, we hypothesize that telocytes may play a crucial role in maintaining biliary homeostasis, and their deficiency may be associated with the development of benign biliary diseases, including gallstone disease and biliary dilation.

Role of Secretory Mucins in the Occurrence and Development of Cholelithiasis.

Cholelithiasis is a common biliary tract disease. However, the exact mechanism underlying gallstone formation remains unclear. Mucin plays a vital role in the nuclear formation and growth of cholesterol and pigment stones. Excessive mucin secretion can result in cholestasis and decreased gallbladder activity, further facilitating stone formation and growth. Moreover, gallstones may result in inflammation and the secretion of inflammatory factors, which can further increase mucin expression and secretion to promote the growth of gallstones. This review systematically summarises and analyses the role of mucins in gallstone occurrence and development and its related mechanisms to explore new ideas for interventions in stone formation or recurrence.

Association of calcific rotator cuff tendinopathy with nephrolithiasis and/or cholelithiasis: A case-control study.

This study aimed to examine the association between calcific rotator cuff tendinopathy (RCT) and nephrolithiasis and/or cholelithiasis. A case-control study was conducted on patients diagnosed with RCT between June 2016 and June 2022. RCT was confirmed by ultrasound, and patients were divided into 2 groups: calcific RCT (case) and non-calcific RCT (control). Data were collected retrospectively from electronic medical records and completed by phone calls, looking for a history of nephrolithiasis and/or cholelithiasis; based on clinical features or incidental findings on abdominal and pelvic imaging. A total of 210 patients with RCT were included. Among the 95 cases of calcific RCT, 43 had a history of lithiasis (45.3%) against 23 (20%) from the non-calcific RCT group (P < .001); 21 patients suffered from nephrolithiasis (22.1%) and 26 had cholelithiasis (27.4%) versus 10 (8.7%) (P = .006) and 16 (13.9%) (P = .015) in the non-calcific RCT group, respectively. Logistic regression showed that the independent predictors of calcific RCT included a history of nephrolithiasis (OR, 4.38; 95% CI: 1.61-11.92, P = .004) and a history of cholelithiasis (OR, 3.83; 95% CI: 1.64-8.94, P = .002). In patients with calcific RCT, the occurrence of lithiasis was significantly associated in the bivariate analysis with higher age, body mass index, fasting blood sugar, and HbA1c (all with P < .05), but only with the presence of another site of calcific tendinopathy than the shoulder (OR, 3.11; 95% CI: 1.12-8.65, P = .03) in the multivariate analysis. Nephrolithiasis and/or cholelithiasis are associated with calcific RCT, and their presence predicts calcific RCT at least 3 times. Further research is required to determine the common risk factors and preventive measures against lithogenesis in patients with calcific RCT, nephrolithiasis, and cholelithiasis.

Correlation Between Blood Levels of Cysteine Protease Caspase-1 (Casp1) and Pain Scores (NRS) Post-surgery: A Prospective Randomized Study of Patients With Cholelithiasis.

BACKGROUND/AIM: Cysteine protease caspase-1 (Casp1) plays a crucial role in the conversion of pro-cytokines to active cytokines (CYTs). The purpose of this work was to determine Casp1 blood levels in a cohort of 114 cholecystectomy patients and assess their association with other CYTs and numeric rating scale (NRS) pain scores, postoperatively. PATIENTS AND METHODS: Blood levels of Casp1 and seven CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-10, IL-1ß, and IL-8) were measured at three time points; before operation, immediately after operation, and six hours after operation in 114 patients with cholelithiasis (Chole). RESULTS: Casp1 blood levels correlated with NRS pain scores at 24 h following surgery (p=0.016). In addition, Casp1 blood levels correlated significantly to IL-18 blood levels (p<0.001). CONCLUSION: This is the first report to evaluate Casp1 blood levels in Chole patients in correlation with other CYTs. The findings confirm a significant correlation between Casp1 blood levels and NRS pain scores. Moreover, this study provides initial evidence suggesting that inhibition of the activity of Casp1 may reduce postsurgical acute phase immune response possibly through the Casp1/pro-Il-18 pathway.

Cholelithiasis in a goat associated with chronic fascioliosis in Bangladesh: A case report and review of literatures.

The objective of the present study was to describe a very rare case of gallstone (cholelithiasis) in a goat associated with chronic fasciolosis. During a routine slaughterhouse-based survey, a two-and-half-year-old female Black Bengal Goat was found to be affected with severe chronic fascioliosis characterized by the massive damage in the liver. Through systemic dissection of liver, we isolated 94 adult Fasciola spp., and by PCR, we confirmed the fluke as Fasciola gigantica. The gallbladder of the goat was oedematous. On opening the gallbladder, we recovered 255 stones of variable sizes. Stones were whitish in colour and friable, and some of the fragile stones were attached to the wall of the gallbladder. To the authors' knowledge, this is the first report of the cholelithiasis in a goat associated with F. gigantica.

Disasters that develop in the liver due to hydatid cyst: a case report.

Hilar cavernous transformation is the formation of venous structures rich in collateral around the portal vein. Portal vein thrombosis is a rare entity. Although there are many reasons for its etiology, few cases have been reported secondary to hydatid cysts in the liver. Here, we present a 24-year-old patient with complaints of abdominal pain and swelling. Her CT and MRI scans show cholelithiasis with portal vein thrombosis and hilar cavernous transformation due to giant hydatid cyst compression in the lateral liver sector.

La transformación cavernosa hiliar es la formación de estructuras venosas ricas en colaterales alrededor de la vena porta. La trombosis de la vena porta es una afección poco frecuente. Aunque existen muchas razones en su etiología, se han descrito pocos casos secundarios a quiste hidatídico en el hígado. Aquí se presenta el caso de una paciente de 24 años con quejas de dolor abdominal e hinchazón. La tomografía computarizada y la resonancia magnética mostraron colelitiasis con trombosis de la vena porta y transformación cavernosa hiliar por compresión del quiste hidatídico gigante en el sector lateral del hígado.

Socially vulnerable patients are more likely to fail outpatient management of symptomatic cholelithiasis.

BACKGROUND: Symptomatic cholelithiasis is a common surgical problem, with many patients requiring multiple gallstone-related emergency department (ED) visits before cholecystectomy. The Social Vulnerability Index (SVI) identifies vulnerable patient populations. This study aimed to assess the association between social vulnerability and outpatient management of symptomatic cholelithiasis. METHODS: Patients with symptomatic cholelithiasis-related ED visits were identified within our health system from 2016 to 2022. Clinical outcomes data were merged with SVI census track data, which consist of 4 SVI subthemes (socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation). Multivariate analysis was used for statistical analysis. RESULTS: A total of 47,292 patients presented to the ED with symptomatic cholelithiasis, of which 6103 patients (13.3 %) resided in vulnerable census tract regions. Of these patients, 13,795 (29.2 %) underwent immediate cholecystectomy with a mean time to surgery of 35.1 h, 8250 (17.4 %) underwent elective cholecystectomy at a mean of 40.6 days from the initial ED visit, and 2924 (6.2 %) failed outpatient management and returned 1.26 times (range, 1-11) to the ED with recurrent biliary-related pain. Multivariate analysis found social vulnerability subthemes of socioeconomic status (odds ratio [OR], 1.29; 95 % CI, 1.09-1.52) and racial and ethnic minority status (OR, 2.41; 95 % CI, 2.05-2.83) to be associated with failure of outpatient management of symptomatic cholelithiasis. CONCLUSION: Socially vulnerable patients are more likely to return to the ED with symptomatic cholelithiasis. Policies to support this vulnerable population in the outpatient setting with timely follow-up and elective cholecystectomy can help reduce delays in care and overutilization of ED resources.

The association between intakes of dietary trace minerals and gallstone disease: A cross-sectional study from National Health and Nutrition Examination Survey 2017 to 2018.

The gallstone disease is becoming increasingly prevalent worldwide. Dietary trace minerals have been proven to be closely related to many metabolic diseases, and this study aims to explore the association between intakes of dietary trace minerals (copper, iron, selenium, and zinc) and gallstone disease (GSD). Using the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018, intakes of dietary trace minerals and GSD data were obtained through a 24-hour recall and diagnostic questionnaire, respectively. Weighted logistic regression models were used to identify the association between intakes of dietary trace minerals and the prevalence of GSD, and the results were presented as odds ratios (OR) and 95% confidence intervals (95% CI). A total of 4077 participants were included in the final analysis, of which 456 participants had GSD and 3621 participants serving as the control group. No significant associations between GSD and intakes of dietary trace minerals (iron, selenium, and zinc) were found. However, after adjusting for all covariates, significant association was demonstrated between dietary copper (Cu) intake and GSD (OR = 0.66, 95% CI = 0.45-0.98). After conducting a weighted quantile logistic regression, a significant negative correlation was also found between dietary Cu intake and highest GSD quartile (Q4) (OR = 0.45, 95% CI = 0.26-0.80). Following the research outlined above, no association was found between intakes of dietary trace minerals (iron, selenium, and zinc) and GSD; however, a linear negative association was identified between dietary Cu intake and GSD.

Investigating the influence of the gut microbiome on cholelithiasis: unveiling insights through sequencing and predictive modeling.

BACKGROUND: Cholelithiasis is one of the most common disorders of hepatobiliary system. Gut bacteria may be involved in the process of gallstone formation and are, therefore considered as potential targets for cholelithiasis prediction. OBJECTIVE: To reveal the correlation between cholelithiasis and gut bacteria. METHODS: Stool samples were collected from 100 cholelithiasis and 250 healthy individuals from Huzhou Central Hospital; The 16S rRNA of gut bacteria in the stool samples was sequenced using the third-generation Pacbio sequencing platform; Mothur v.1.21.1 was used to analyze the diversity of gut bacteria; Wilcoxon rank-sum test and linear discriminant analysis of effect sizes (LEfSe) were used to analyze differences in gut bacteria between patients suffering from cholelithiasis and healthy individuals; Chord diagram and Plot-related heat maps were used to analyze the correlation between cholelithiasis and gut bacteria; six machine algorithms were used to construct models to predict cholelithiasis. RESULTS: There were differences in the abundance of gut bacteria between cholelithiasis and healthy individuals, but there were no differences in their community diversity. Increased abundance of Costridia, Escherichia flexneri, and Klebsiella pneumonae were found in cholelithiasis, while Bacteroidia, Phocaeicola, and Phocaeicola vulgatus were more abundant in healthy individuals. The top four bacteria that were most closely associated with cholelithiasis were Escherichia flexneri, Escherichia dysenteriae, Streptococcus salivarius, and Phocaeicola vulgatus. The cholelithiasis model based on CatBoost algorithm had the best prediction effect (sensitivity: 90.48%, specificity: 88.32%, and AUC: 0.962). CONCLUSION: The identification of characteristic gut bacteria may provide new predictive targets for gallstone screening. As being screened by the predictive model, people at high risk of cholelithiasis can determine the need for further testing, thus enabling early warning of cholelithiasis.

[Clinical and economic justification of icg-cholangiography in «difficult¼ laparoscopic cholecystectomy]. / Kliniko-ekonomicheskoe obosnovanie kholangiografii s indotsianinom zelenym pri «trudnoi¼ laparoskopicheskoi kholetsistektomii.

OBJECTIVE: To prove from a clinical and economic point of view the expediency of using ICG cholangiography in patients with «difficult¼ laparoscopic cholecystectomy for the prevention of damage to the bile ducts. MATERIAL AND METHODS: The results of treatment of 173 patients with cholelithiasis at various levels of health care providing were analyzed with regard to assessment of indicators of surgery complexity, developed complications and economic costs. RESULTS: The effectiveness of the original scale of «difficult¼ laparoscopic cholecystectomy has been proved. The financial and economic costs of treatment of patients with damage of biliary ducts and patients with cholelithiasis without development of complications have been analyzed and evaluated. A comparative description of financial costs for patients with «difficult¼ laparoscopic cholecystectomy with the use of ICG-cholangiography has been given. A program on care delivery for patients suffering from cholelithiasis in the conditions of region with regard to safety and economic effectiveness has been developed. CONCLUSION: The implementation of this program provides the minimization of postoperative complications and fatality at all levels of surgical care delivery. It has been established that a rational approach to reducing the number of biliary ducts damages is their prevention by prediction of «difficult¼ laparoscopic cholecystectomy and performance of such interventions in medical organizations of III level with the possibility of modern technologies use.

[New Progress in Longitudinal Research on the Risk Factors for Cholelithiasis]. / åŸºäºŽçºµå‘ç ”ç©¶çš„èƒ†å›Šç»“çŸ³å‘ç— é£Žé™©å› ç´ ç ”ç©¶æ–°è¿›å±•.

Cholelithiasis is a common disease of the digestive system. The risk factors for cholelithiasis have been reported and summarized many times in the published literature, which primarily focused on cross-sectional studies. Due to the inherent limitations of the study design, the reported findings still need to be validated in additional longitudinal studies. Moreover, a number of new risk factors for cholelithiasis have been identified in recent years, such as bariatric surgery, hepatitis B virus infection, hepatitis C virus infection, kidney stones, colectomy, osteoporosis, etc. These new findings have not yet been included in published reviews. Herein, we reviewed the 101 cholelithiasis-associated risk factors identified through research based on longitudinal investigations, including cohort studies, randomized controlled trials, and nested case control studies. The risk factors associated with the pathogenesis of cholelithiasis were categorized as unmodifiable and modifiable factors. The unmodifiable factors consist of age, sex, race, and family history, while the modifiable factors include 37 biological environmental factors, 25 socioenvironmental factors, and 35 physiochemical environmental factors. This study provides thorough and comprehensive ideas for research concerning the pathogenesis of cholelithiasis, supplying the basis for identifying high-risk groups and formulating relevant prevention strategies.

TyG index is positively associated with HOMA-IR in cholelithiasis patients with insulin resistance: Based on a retrospective observational study.

BACKGROUND/OBJECTIVE: Cholelithiasis is a common disease but pose significant global health and financial burdens. Mechanisms of the disease are associated with insulin resistance (IR), obesity, metabolic syndrome, and type 2 diabetes. Insulin resistance is commonly observed in cholelithiasis patients. More recently, the triglyceride-glucose (TyG) index has been proposed as an alternative marker of insulin resistance. In our study we aimed to understand whether the TyG index is correlated with HOMA-IR in cholelithiasis patients. And also we aimed the predict a cutoff value for determining insulin resistance in cholelithiasis patients. METHODS: A total of 184 cholelithiasis patients were matched in terms of age, gender, and BMI. They were divided into two groups based on their Homa IR levels (IR and Non-IR group). This study was a retrospective, observational study and clinical data was obtained from electronic medical records. Cutoff value for Tyg index was established through ROC Analysis. Binary Logistic Regression was used to identify factors affecting insulin resistance. RESULTS: A significant cutoff value was found for the TyG index in determining the presence of insulin resistance. Having a TyG index of ≥8.71 indicates the presence of insulin resistance. The sensitivity was 68.48%, the specificity was 58.70%. Binary Logistic Regression analyses showed that an increase in Tyg Index, waist circumference and waist-to-height ratio values increases the risk of insulin resistance by 2.705 (p = 0.001), 1.032 (p = 0.029), and 334.057 (p = 0.012) times respectively. CONCLUSION: Our study indicated that TyG index is positively correlated with HOMA-IR. TyG index was found as a risk factor for insulin resistance.

CLINICAL AND PATHOLOGIC FINDINGS IN IGUANIDS WITH SODIUM URATE CHOLELITHIASIS.

Four green iguanas (Iguana iguana) and one blue iguana (Cyclura lewisi) from five facilities were diagnosed with sodium urate cholelithiasis. One case was diagnosed antemortem via ultrasonography, and the iguana underwent a choledochotomy for treatment. The other four cases were identified at necropsy. Pathologic hepatic and biliary changes were present in four of the five cases at necropsy. Histologically, four iguanas had hepatic fibrosis, three had bile duct hyperplasia, and one had cholangiohepatitis and pancreaticocholedochitis. Two iguanas had pathologic renal changes. This is the first report of sodium urate cholelithiasis in reptiles. This case series highlights the potential significant clinical disease caused by sodium urate cholelithiasis and the importance of biliary system evaluation. Further investigation is recommended to explore the pathogenesis of reptilian sodium urate cholelith formation.

Endoscopic features of low-phospholipid-associated cholelithiasis syndrome: A retrospective cohort study.

BACKGROUND AND OBJECTIVE: LPAC (low phospholipid-associated cholelithiasis) syndrome is a rare genetic form of cholelithiasis. ERCP (endoscopic retrograde cholangiopancreatography) is often used to remove gallstones in the bile duct. No published data is available on the role of ERCP in LPAC syndrome. PATIENTS AND METHODS: In this retrospective cohort study, we included patients diagnosed with LPAC syndrome in a single tertiary referral center between 2009 and 2021. Our aim was to assess the frequency, indications, modalities, results, and complications of ERCP, as well as predictive factors for ERCP, in LPAC syndrome. Independent factors associated with ERCP occurrence were identified using a multivariable Cox regression analysis. RESULTS: ERCP was required in 31.2 % of the 269 patients included for analysis. Among patients who required ERCPs, 78.6 % had the procedure before diagnosis (i.e., starting UDCA). Most common indications were choledocholithiasis (53.6 %) and acute cholangitis (29.5 %). Post ERCP pancreatitis, perforation and bleeding rates were 7.2 %, 2.6 %, and 1.3 %, respectively. Age and history of cholelithiasis in first-degree relatives were associated with a higher risk of ERCP (Hazard-ratio [HR]=1.30 [95 %confidence-interval [CI] 1.04-1.62] and HR=1.88 [95 %CI 1.15-3.07] respectively). Female gender and UDCA intake ≥ 1 year were associated with a lower risk of ERCP (HR=0.49 [95 %CI 0.29-0.82] and HR=0.44 [95 %CI 0.22-0.90] respectively). Median follow-up was 10.8 years. CONCLUSION: One-third of patients with LPAC syndrome undergo sphincterotomy. However, most procedures are performed before diagnosis and UDCA is associated with a lower risk of endoscopic procedure. Earlier diagnosis and treatment with UDCA may further reduce the need for ERCP in patients with LPAC syndrome.

Association between sarcopenia-related markers and cholelithiasis: A prospective and Mendelian randomization study.

Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.

Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses.

Background: General obesity is a well-established risk factor for gallstone disease (GSD), but whether central obesity contributes additional independent risk remains controversial. We aimed to comprehensively clarify the effect of body fat distribution on GSD. Methods: We first investigated the observational association of central adiposity, characterized by waist-to-hip ratio (WHR), with GSD risk using data from UK Biobank (N=472,050). We then explored the genetic relationship using summary statistics from the largest genome-wide association study of GSD (ncase=43,639, ncontrol=506,798) as well as WHR, with and without adjusting for body mass index (BMI) (WHR: n=697,734; WHRadjBMI: n=694,649). Results: Observational analysis demonstrated an increased risk of GSD with one unit increase in WHR (HR=1.18, 95%CI=1.14-1.21). A positive WHR-GSD genetic correlation (rg =0.41, P=1.42×10-52) was observed, driven by yet independent of BMI (WHRadjBMI: rg =0.19, P=6.89×10-16). Cross-trait meta-analysis identified four novel pleiotropic loci underlying WHR and GSD with biological mechanisms outside of BMI. Mendelian randomization confirmed a robust WHR-GSD causal relationship (OR=1.50, 95%CI=1.35-1.65) which attenuated yet remained significant after adjusting for BMI (OR=1.17, 95%CI=1.09-1.26). Furthermore, observational analysis confirmed a positive association between general obesity and GSD, corroborated by a shared genetic basis (rg =0.40, P=2.16×10-43), multiple novel pleiotropic loci (N=11) and a causal relationship (OR=1.67, 95%CI=1.56-1.78). Conclusion: Both observational and genetic analyses consistently provide evidence on an association of central obesity with an increased risk of GSD, independent of general obesity. Our work highlights the need of considering both general and central obesity in the clinical management of GSD.