Risk Of Gallbladder Disease Research Articles

Physical Activity and the Biliary Tract in Health and Disease

Cholecystitis and gallstones affect a large segment of the population in developed nations, and a small proportion of affected individuals subsequently develop cancer of the gallbladder. However, little is known about the possible beneficial effects of physical activity. Accordingly, a systematic review examined the influence of both acute and chronic exercise on gallbladder motility, and relationships were examined between habitual physical activity, gallbladder disease, and gallbladder cancer. A search of Ovid/MEDLINE from 1996 to November 2014 yielded 67 articles relating to physical activity and gallbladder function or disease; 18 of these relevant to the objectives of the review were supplemented by 22 papers from personal files and other sources. Because of the limited volume of material, all were considered, although note was taken of the quality of activity measurement, care in excluding covariates, and experimental design (cross-sectional, case-control or randomized controlled trial). The impact of physical activity upon gallbladder function remains unclear; acute activity could augment emptying by stimulating cholecystokinin release, and one of two training experiments found a small increase in gallbladder motility. The largest and most recent cross-sectional and case-control trials show a reduced risk of gallbladder disease in active individuals. A small number of randomized controlled trials in humans and one animal study generally support these trends, although the number of cases of gallstones are too few for statistical significance. Three studies of gallbladder cancer also show a non-significant trend to benefit from physical activity. Although there remains a need for further research, regular physical activity seems likely to reduce the risk of both gallstones and gallbladder cancer. A substantial number of individuals must be persuaded to exercise in order to avoid one case of gallbladder disease, but the attempt appears warranted because of the other health benefits of regular physical activity.

Lipids, obesity and gallbladder disease in women: insights from genetic studies using the cardiovascular gene-centric 50K SNP array.

Gallbladder disease (GBD) has an overall prevalence of 10–40% depending on factors such as age, gender, population, obesity and diabetes, and represents a major economic burden. Although gallstones are composed of cholesterol by-products and are associated with obesity, presumed causal pathways remain unproven, although BMI reduction is typically recommended. We performed genetic studies to discover candidate genes and define pathways involved in GBD. We genotyped 15 241 women of European ancestry from three cohorts, including 3216 with GBD, using the Human cardiovascular disease (HumanCVD) BeadChip containing up to ~53 000 single-nucleotide polymorphisms (SNPs). Effect sizes with P-values for development of GBD were generated. We identify two new loci associated with GBD, GCKR rs1260326:T>C (P=5.88 × 10−7, ß=−0.146) and TTC39B rs686030:C>A (P=6.95x10−7, ß=0.271) and detect four independent SNP effects in ABCG8 rs4953023:G>A (P=7.41 × 10−47, ß=0.734), ABCG8 rs4299376:G>T (P=2.40 × 10−18, ß=0.278), ABCG5 rs6544718:T>C (P=2.08 × 10−14, ß=0.044) and ABCG5 rs6720173:G>C (P=3.81 × 10−12, ß=0.262) in conditional analyses taking genotypes of rs4953023:G>A as a covariate. We also delineate the risk effects among many genotypes known to influence lipids. These data, from the largest GBD genetic study to date, show that specific, mainly hepatocyte-centred, components of lipid metabolism are important to GBD risk in women. We discuss the potential pharmaceutical implications of our findings.

Dietary patterns and risk of gallbladder disease: a hospital-based case-control study in adult women.

Gallbladder disease is one of the most prevalent gastrointestinal disorders that may result from a complex interaction of genetic and environmental factors. This study examined the association of dietary patterns with gallstone disease among Iranian women. This case-control study was conducted in general teaching hospitals in Tehran, Iran. Participants were 101 female cases and 204 female controls aged 40-65 years who were admitted for problems other than GBD. Dietary patterns were identified using principal components analysis based on food frequency questionnaire. Compared to the control group, cases were less educated, less physically active, and consumed more total energy (p<0.02). Having ≥ 3 livebirths increased the risk of gallstone by more than 5 times, followed by having rapid weight loss, being single, having familial history of gallstone, and consuming high total energy. Two distinct dietary patterns were identified in women (healthy and unhealthy). After adjustment for several confounding variables, healthy dietary pattern was associated with a decreased risk of gallstone disease (OR=0.14, 95% CI 0.048-0.4) while unhealthy dietary pattern was associated with an increased risk (OR=3.77, 95% CI 1.52-9.36). These findings confirm that dietary pattern approach provides potentially useful and relevant information on the relationship between diet and disease. Identifying risk factors will provide an opportunity for prevention of gallbladder disease in developing countries facing an increased risk of obesity.

Serum estrogen level and lipid profile in Gall stone and Gallbladder cancer: a case control study

Background: Carcinoma of the gallbladder is a highly fatal disease with late diagnosis, limited treatment options and deprived prognosis. It is the fifth most common cancer of gastrointestinal tract and the most common cause of death from biliary malignancies. In postmenopausal women, hormone replacement therapy significantly increases the risk of gallbladder diseases. Gallstones and gallbladder cancer predominate in females and are associated with obesity and multiple pregnancies. In the present study, we have estimated the Level of Estradiol and Lipid profile in different study groups and healthy controls from northern India. Results: The estradiol level was significantly (p 0.001) higher among patients with gall bladder cancer and stone both, gallbladder stone, gall bladder cancer compared with controls. The lipid profile and estradiol levels were almost similar among males in both study and control group while significantly different among females. Conclusions: These results indicate that the female gender is strongly associated with disease and the possible reason is increased level of total cholesterol, triglyceride, low density lipoprotein and very low density lipoprotein and decreased level of high density lipoprotein, and also the higher level of estrogen.

Relationship Between Gallbladder Surgery and Ethnic Admixture in African American and Hispanic American Women

The objective of this study was to investigate whether differences in admixture in African American and Hispanic American adult women are associated with differences in gallbladder surgery. Gallbladder surgery history on entry to the Women's Health Initiative's (WHI) study was used as a dichotomous outcome measure for this study. The proportion of European, sub-Saharan African, and Amerindian (AMI) admixture was estimated for 10,841 African American and 4,620 Hispanic American women in WHI using 92 ancestry informative markers. Logistic regression analyses assessed the relationship between admixture and gallbladder surgery in WHI women (enrollment at ages >50, mean age 61 years) with or without adjusting for multiple covariates, including measures of adiposity, parity, alcohol use, and education. There was a significant positive association between AMI admixture and the frequency of gallbladder surgery in Hispanic Americans. The odds ratio (OR) and 95% confidence intervals (CIs) for AMI admixture group was OR=2.97, CI=2.01-4.38, P<10(-4). Although there were strong positive associations with parity and adiposity, and negative associations with alcohol consumption and education, accounting for these covariates did not remove the admixture association (OR=2.46, CI=1.62-3.73). In contrast, the effect of African admixture was nearly indistinguishable from that of the European admixture, both of which were protective in the Hispanic American group, and African admixture had a marginal association with decreased gallbladder surgery in the African American group. Measures of adiposity were associated with increased risk for gallbladder surgery and remained significant after accounting for admixture and each of the other covariates. Education level and alcohol use were associated with decreased risk for gallbladder disease. However, after accounting for the other covariates these variably remained significant. AMI admixture is strongly associated with gallbladder surgery in women, even after adjustment for selected risk factors for cholelithiasis. Additional studies to ascertain the specific genetic risk factors underlying these associations are warranted.

Drospirenone- and levonorgestrel-containing oral contraceptives and the risk of gallbladder disease

BackgroundStudies have found an association between the use of estrogen-containing oral contraceptives (OCs) and the risk of gallbladder disease. This study evaluated this relation as well as the role of progestogen on the risk of gallbladder disease among users of drospirenone-containing OCs compared to users of levonorgestrel-containing OCs. Study DesignDatabase: The UK General Practice Research Database.We conducted a nested case–control analysis among women aged 14 to 60 years during 2001 through 2008 who had ever received drospirenone- or levonorgestrel-containing OCs. Cases were women with a first diagnosis of gallbladder disease during the study period. Women who received a study OC within 6 months of the index date were exposed. All other women were nonexposed. We matched two controls to each case on year of birth, index date, amount of recorded history and general practice attended. ResultsThe adjusted odds ratio for gallbladder disease comparing drospirenone and levonorgestrel OCs to nonexposure were 0.9 [95% confidence interval (CI) 0.7–1.1] and 1.0 (95% CI 0.9–1.1), respectively. ConclusionsThere is no evidence in these data that drospirenone- or levonorgestrel-containing OC use confers an increased risk of gallbladder disease compared to women not currently exposed to an OC. Nor is use of drospirenone OCs associated with a higher risk of gallbladder disease than use of levonorgestrel-containing OCs.

Oral contraceptives and risk of gallbladder disease

We agree with Wang and colleagues that the risk of gallbladder disease with the use of oral contraceptives may be modified by different levels of BMI.[1][1] Unfortunately, information on BMI was not available for our study.[2][2] We agree that future research should examine this issue carefully. 1

Oral contraceptives and risk of gallbladder disease

Etminan and colleagues reported on an interesting study in which they found merely a little association between the use of oral contraceptives and gallbladder disease.[1][1] This resembled the results of our recently completed observational study (unpublished data: 2011) in which the cumulative

High Carb Intake Raises Gallbladder Disease Risk

High Carb Intake Raises Gallbladder Disease Risk

Population-based study to estimate prevalence and determine risk factors of gallbladder diseases in the rural Gangetic basin of North India

BackgroundA high prevalence of gallbladder diseases (GBD) in Northern India warranted a population survey into environmental risk factors. MethodsIn 60 villages of Uttar Pradesh and Bihar from 13 334 households, 22 861 persons aged >30 years were interviewed for symptoms of GBD, diet and environmental factors. Subsequently ultrasonography (US) was performed in 5100 and 1448 people with and without symptoms, respectively. Heavy metal and pesticide content in soil and water were estimated. ResultsUS revealed a prevalence of GBD of 6.20%. GBD was more common in 5100 persons with symptoms (7.12%) compared with 1448 without (2.99%) (P < 0.05). Adjusted odds ratio (ORs) [95% confidence interval (CI)] revealed a significantly increased risk of GBD in females >50, 1.703 (CI 1.292–2.245); multiparity 1.862 (CI 1.306–2.655) and a genetic history 1.564 (CI 1.049–2.334). An increased risk noted in males with diabetes was 4.271 (CI 2.130–8.566), chickpea consumption 2.546 (CI 1.563–4.146) and drinking unsafe water 3.835 (CI 2.368–6.209). Prevalence of gallstones was 4.15%; more in females 5.59% than males 1.99% (P < 0.05). Cluster analysis identified a positive correlation of nickel, cadmium and chromium in water with a high prevalence of GBD in adjacent villages in Vaishali district, Bihar. ConclusionA high risk of GBD was observed in older, multiparous women and men with diabetes, intake of chickpeas, unsafe water and villages with heavy metal water pollution.

Separate and Joint Effects of Alcohol and Smoking on the Risks of Cirrhosis and Gallbladder Disease in Middle-aged Women

The separate and joint effects of alcohol and smoking on incidences of liver cirrhosis and gallbladder disease were examined in a prospective study of 1,290,413 United Kingdom women (mean age, 56 years) recruited during 1996-2001. After a mean follow-up of 6.1 years (1996-2005), incidence rates of cirrhosis and gallbladder disease were 1.3 per 1,000 persons (n = 2,105) and 15 per 1,000 persons (n = 23,989), respectively, over 5 years. Cirrhosis risk increased with increasing alcohol consumption, while the risk of gallbladder disease decreased (P(trend) < 0.0001 for each). Comparing women who drank > or =15 units/week with those who drank 1-2 units/week, the relative risk was 4.32 (95% confidence interval (CI): 3.71, 5.03)) for cirrhosis and 0.59 (95% CI: 0.55, 0.64) for gallbladder disease. Increasing numbers of cigarettes smoked daily increased the risk of both conditions (P(trend) < 0.0001 for each). Comparing current smokers of > or =20 cigarettes/day with never smokers, the relative risk was 3.76 (95% CI: 3.25, 4.34) for cirrhosis and 1.29 (95% CI: 1.22, 1.37) for gallbladder disease. Effects of alcohol and smoking were more than multiplicative for cirrhosis (P(interaction) = 0.02) but not for gallbladder disease (P(interaction) = 0.4). Findings indicate that alcohol and smoking affect the risks of the 2 conditions in different ways. For cirrhosis, alcohol and smoking separately increase risk, and their joint effects are particularly hazardous. For gallbladder disease, alcohol reduces risk and smoking results in a small risk increase.

Greater risk of gallbladder disease in postmenopausal women using oral vs transdermal HRT

Greater risk of gallbladder disease in postmenopausal women using oral vs transdermal HRT

Childbearing, breastfeeding, other reproductive factors and the subsequent risk of hospitalization for gallbladder disease

While parous women are known to be at an increased risk of gallbladder disease, little is known about the effects of other reproductive factors such as breastfeeding, age at menarche and age at menopause. The Million Women Study is a prospective cohort study of 1.3 million middle-aged women in England and Scotland recruited from 1996 to 2001. Participants were followed-up by record-linkage for a mean of 6.1 years for admissions to hospital. The adjusted relative risk of hospital admission for cholelithiasis, cholecystitis or cholecystectomy according to parity, breastfeeding, age at menarche and age at menopause was examined. During follow-up of 1 289 029 eligible women, 25 111 were admitted to hospital for gallbladder disease, of whom 21 735 (87%) had a cholecystectomy. The hospital admission rate over 5 years for gallbladder disease was 1.6/100 women and for cholecystectomy was 1.4/100 women. The adjusted relative risk of gallbladder disease increased with increasing parity by 8% (95% CI 7-9%, P < 0.0001) for each birth. Among women of a given parity, breastfeeding reduced the risk of gallbladder disease, the relative risk decreasing by 7% (95% CI 5-10%, P < 0.0001) per year of breastfeeding. Women's age of menarche and age at menopause did not alter the risk of gallbladder disease (P = 0.4 and P = 0.3, respectively for linear trend). Hospitalization for gallbladder disease is common in middle-aged women. The risk increases the more children a woman has had, but decreases the longer she breastfeeds. The increased risk of gallbladder disease associated with having children can be offset by breastfeeding.

Transdermal hormonal replacement is associated with a markedly lower risk of gall bladder disease (GBD) than oral administration,

Transdermal hormonal replacement is associated with a markedly lower risk of gall bladder disease (GBD) than oral administration,

Independent Effects of Cardiorespiratory Fitness, Vigorous Physical Activity, and Body Mass Index on Clinical Gallbladder Disease Risk

Incident self-reported physician-diagnosed clinical gallbladder disease was compared to BMI, body dimensions, physical activity (km/day run) and cardiorespiratory fitness (10 km race speed, meters per second [m/s]) in 29,110 male and 11,953 female runners. Physician-diagnosed gallbladder disease was reported by 166 men (0.57%) and 112 women (0.94%) during (mean +/- SD) 7.74 +/- 1.84 and 7.42 +/- 2.10 years of follow-up, respectively. There was a progressive increase in age-adjusted risk with increasing BMI that accelerated sharply above 27.5 kg/m(2). Even among ostensibly healthy-weight women, the age-adjusted risk was significantly greater above 22.5 kg/m(2) vis-à-vis the leanest women (P= 0.04). Age-adjusted risk declined with increasing fitness in both sexes. Compared to the least fit men and women, men who ran faster than 4.75 m/s had 83% lower risk (75% lower when adjusted for km/day and BMI) and women who ran faster than 4 m/s had 93% lower risk (85% lower adjusted for km/day and BMI). The fittest men (> or =4.75 m/s) were at significantly less risk than men who ran <3.25 m/s (P < 0.003) and between 3.25 and 3.75 m/s (P= 0.03), and the fittest women (> or =4 m/s) were at significantly less risk than those who ran <2.8 m/s (P < 0.0001), between 2.8 and 3.2 (P= 0.0004), 3.2 and 3.6 (P= 0.002), and 3.6 and 4.0 m/s (P= 0.005). Adjustment for BMI accounted for more of the risk reduction associated with fitness in women than men. The risk for clinical gallbladder disease was also significantly related to usual running distance (men: P= 0.01; females: P= 0.008), which was attributable to the leanness of the longer-distance runners. Clinical gallbladder disease risk was (a) concordantly related to BMI, (b) inversely related to usual running distance, and (c) inversely related to cardiorespiratory fitness independent of physical activity levels.

Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study

Objective To determine whether transdermal compared with oral use of hormone replacement therapy reduces the risk of gallbladder disease in postmenopausal women.Design Prospective cohort study (Million Women Study).Setting Women registered...

Hormone Replacement Therapy and Symptomatic Gallstones – A Prospective Population Study in the EPIC-Norfolk Cohort

Background/Aims: Hormone replacement therapy (HRT) may increase the risk of symptomatic gallstones, but this association has not been investigated in a prospective study in a European population. The aim of the study was to investigate the relationship between HRT and the development of symptomatic gallstones in a free-living population. Methods: Use of HRT was ascertained by questionnaire in 13,433 women aged 45–74 years living in Norfolk, UK, who participated in the EPIC-Norfolk Study (European Prospective Investigation Into Cancer). The use of HRT was that at the time of recruitment rather than at the point of diagnosis. Participants were followed up for the development of symptomatic gallstones. The analysis used a nested case-control method in a prospective study. Results: A total of 117 women developed symptomatic gallstones. Women who reported either ever using HRT, currently using HRT or who had been past users all had a greater risk of gallbladder disease than age-matched control women who had never used HRT, after adjusting for known risk factors for gallstones. Women who had ever used HRT had a risk of 1.94 (95% CI = 1.17–3.22) compared with women who had never used HRT. For past users of HRT, the risk of symptomatic gallstones was greater, the longer the duration of use (OR = 4.05, 95% CI = 1.12–14.76 for use >1 year, compared to OR = 2.04, 95% CI = 0.79–5.30 for ≤1 year). Conclusions: Use of HRT was positively associated with an increased risk of symptomatic gallstones in this population. This confirms trial data and additionally shows effects of duration of use and increased risk associated with past use.

Oral Estrogen Not Gallbladder-Friendly; Transdermal Seems Better

Hormone therapy raises risk for gallbladder disease — but does the route of administration matter? In the Million Women Study, U.K. investigators prospectively analyzed self-reported HT use in a cohort of 1.3 million postmenopausal women (age range, 50–69) and their rate of hospital admissions for gallbladder disease or cholecystectomy (determined through linkage to National Health Service data) during a mean follow-up of 6 years. Among those who used HT, about four times more women used …

Physical Activity and Gallbladder Disease Determined by Ultrasonography

Several prospective studies have suggested that physical activity may decrease the risk for symptomatic gallbladder disease. None of these studies were able to include subjects with asymptomatic gallstones in their case group. This investigation examined the relationship between physical activity levels and the development of gallbladder disease determined by ultrasonography in a population-based cohort of 3143 men and women, 45-74 yr of age, from 13 American Indian communities. Participants were examined at baseline (1989-1992), at which time physical activity levels, age, body mass index, waist circumference, smoking status, and diabetes status were determined. Gallbladder disease status was assessed in the entire cohort at follow-up (1993-1995) by ultrasonography. Individuals who reported at baseline that they had gallbladder surgery or that a physician had told them that they had gallbladder disease were removed from the analyses. Out of the 2130 remaining, 650 individuals (403 women and 247 men) were found to have gallbladder disease according to ultrasound or reported surgery by the follow-up clinic visit. After adjusting for potential confounders including body mass index, increased activity levels were inversely related to gallbladder disease status. These findings were maintained when the data were stratified by sex, but they were only significant in individuals without diabetes (not in those with diabetes). Physical activity seems to be significantly and inversely related to the development of gallbladder disease as assessed by ultrasonography in a population at high risk for gallbladder disease. These findings add to the evidence supporting a causal link between physical activity levels and a decreased risk of gallbladder disease, and they provide yet another reason to encourage the achievement and maintenance of a physically active lifestyle.

Genetic evidence that apolipoprotein E4 is not a relevant susceptibility factor for cholelithiasis in two high-risk populations

Apolipoprotein E (apoE) isoforms are genetic determinants of interindividual variations in lipid metabolism. To assess whether apoE is a genetic risk factor for cholesterol gallstone disease (GD), we analyzed apoE variants in populations from Chile and Germany, two countries with very high prevalence rates of this disease. ApoE genotypes were determined in Chilean gallstone patients (n = 117) and control subjects (n = 122) as well as in German gallstone patients (n = 184) and matched controls (n = 184). In addition, we studied apoE variants in subgroups of Chilean patients with strong differences in their susceptibility to acquire gallstones: 50 elderly subjects without gallstones in spite of well-known risk factors for this disease (gallstone-resistant) and 32 young individuals with gallstones but without risk factors (gallstone-susceptible). Furthermore, correlation analysis of apoE genotypes with cholesterol crystal formation times, biliary cholesterol saturation index (CSI), and gallstone cholesterol contents was performed in 81 cholecystectomized patients. In this study analyzing the largest sample set available, apoE4 genotype was not associated with an increased frequency of GD in either population. Moreover, in the Chilean population after adjusting for risk factors such as gender, age, body mass index, serum lipids, and glucose, the odds ratio for the association of the apoE4 allele and GD was significantly (P < 0.05) <1. Also, genotypes were not correlated with cholesterol crystal formation time, CSI, or gallstone cholesterol content. In contrast to previous smaller studies, apoE polymorphisms were not associated with susceptibility to cholesterol GD in high-risk populations.