Apolipoprotein E polymorphism and gallstones

BACKGROUND & AIMS: Apolipoprotein (apo) E is a genetically polymorphic protein influencing lipoprotein metabolism and the risk of both atherosclerosis and Alzheimer's disease. As opposed to common apo E3, apo E2 decreases and apo E4 increases hepatic lipoprotein uptake; hence, apo E4 could promote gallstone formation by increasing hepatic and biliary cholesterol concentrations. This study was designed to evaluate whether apo E polymorphism is related to gallstone risk. METHODS: apo E phenotype was determined in subjects older than 40 years of age (160 with and 125 without gallstones) and in 61 patients with cholesterol gallstones who underwent cholecystectomy. Bile composition, nucleation time, and gallstone features were analyzed in surgical patients. RESULTS: The E4/3 phenotype was enriched in both patients with gallstones and those who underwent cholecystectomy, with significantly (P < 0.006) higher epsilon 4 allele frequencies than in gallstone-free subjects (odds ratio, 2.67 [95% confidence limits, 1.23- 5.93] and 3.62 [95% confidence limits, 1.49-8.91], respectively); women, but not men, accounted for these differences. The prevalence of the epsilon 4 allele increased with age in patients with gallstones, whereas the opposite occurred in gallstone-free subjects. Biliary lipid and gallstone cholesterol content tended to increase in the sequence E4 > E3 > E2 in patients who underwent cholecystectomy. CONCLUSIONS: Carrying the apo E4 isoform is a genetic risk factor for cholelithiasis in humans, thus adding another adverse effect of apo E polymorphism on health. (Gastroenterology 1996 Dec;111(6):1603-10)     

Hepatitis C virus infection is a risk factor for gallstone disease: a prospective hospital-based study of patients with chronic viral C hepatitis

Summary.  We evaluated the prevalence and the risk factors for gallstone disease in patients with chronic hepatitis C infection. We investigated 453 consecutively admitted patients with chronic infection with hepatitis C virus (HCV) (cirrhosis excluded) and 879 patients without liver disease (October 2006–April 2007). Gallstone disease was diagnosed if gallstones were present at ultrasonography or if there had been a previous cholecystectomy. Variables evaluated were age, gender, gallstone heredity, body mass index, waist circumference, parity, serum lipids, fatty liver, arterial hypertension, diabetes mellitus and metabolic syndrome (International Diabetes Federation criteria). Informed consent was obtained from all patients. We found that 88 of 453 (19%) patients with chronic HCV hepatitis (age 50.1 ± 11.7 years) and 153 of 879 (17%) controls (age 60.6 ± 12.6 years) had gallstone disease (GD). Abdominal obesity (OR = 2.108, 95% CI 1.287–3.452) and steatosis (OR = 3.699, 95% CI 2.277–6.008) were risk factors for GD in HCV patients. Gallstone heredity, dyslipidaemia, type 2 diabetes mellitus and metabolic syndrome increased the risk for GD in controls vs HCV patients. Our study shows that even HCV patients with chronic hepatitis but not cirrhosis have an increased prevalence of gallstones. Compared with controls, gallstones are present in HCV patients at a younger age and are associated with central obesity and liver steatosis, but not with gallstone heredity, dyslipidaemia, diabetes mellitus or metabolic syndrome. Although we could not establish a temporal relationship, the association between HCV infection and gall stone disease is real and appears to be causally linked, at least in predisposed individuals (obese and with liver steatosis).     

Portal venous bile acids in cholesterol gallstone disease: effect of treatment with chenodeoxycholic and cholic acids

We determined the serum concentrations of cholic, chenodeoxycholic and deoxycholic acids in portal and peripheral venous blood in 9 gallstone-free patients and 39 patients with cholesterol gallstones during standardized cholecystectomy. An accurate and specific gas chromatographic-mass spectrometric technique was used. The portal venous concentration of total bile acids was similar in gallstone-free and untreated gallstone patients (n = 20); there was no evidence of a reduced hepatic uptake of bile acids in the latter. Treatment with cholic acid (n = 10) was associated with a 70% increase in cholic acid and normal concentration of total bile acids. In chenodeoxycholic acid-treated patients (n = 9), the portal venous concentration of this bile acid was increased 3-fold; total bile acids were increased about 60%. The estimated hepatic uptake of cholic acid was slightly decreased during chenodeoxycholic acid treatment. The results indicate that neither bile acid inflow to the liver nor hepatic bile acid uptake is reduced in fasting patients with cholesterol gallstones, and treatment with chenodeoxycholic acid increases fasting inflow of bile acids to the liver. The latter may contribute to unsaturation of fasting hepatic bile during treatment with chenodeoxycholic acid.     

The prevalence of gallstone disease in a defined cohort of patients with Crohn's disease

OBJECTIVE: Crohn's disease (CD) is associated with a high prevalence of gallstone disease but the relative risk has not been completely established. Ileal disease or resection have been considered as contributing factors to the increased risk. The aim of this study was to evaluate the prevalence of gallstone disease in a defined cohort of CD patients, to evaluate possible risk factors, and to evaluate the relative risk compared with the general population. METHODS: All inhabitants in Stockholm County born in 1933-1935 or 1953-1955, with CD diagnosed between 1955-1989 and not having had a previous cholecystectomy, were invited for an ultrasonography of the gallbladder. The prevalence of gallstone disease was related to disease extent, previous intestinal resections, age, and gender. The relative risk of developing gallstones was calculated using a recent study of gallstone disease in general, with similar age groups as controls. RESULTS: We found that 26.4% had gallstone disease (relative risk [RR] = 1.8; 95% confidence interval [CI], 1.2-2.7). The number of previous intestinal resections was the only significant risk factor. There was no significant difference in gallstone disease between gender (28.2% vs 24.1%) or age (34% vs 21.8%). CONCLUSIONS: Patients with Crohn's disease, regardless of gender and age, have almost a doubled risk of developing gallstone disease compared with the general population. Circumstances related to laparotomy may contribute to the increased risk. The lack of association between the disease extent and the site of previous intestinal resection, together with a previous finding of normal cholesterol saturation of the bile in patients with CD, indicate that these patients may develop pigment stones rather than cholesterol stones.     

Surgical practice in symptomatic and asymptomatic gallstone disease.

AIMS: To determine the surgical practice in individuals with symptomatic and asymptomatic gallstone disease using a questionnaire survey. METHODS: A questionnaire was sent to 724 patients with gallstone disease. Details of symptoms, duration of illness, nature of treatment including surgery, color of gallstones retrieved and postoperative follow-up particulars were obtained. RESULTS: The study group included 225 (54%) men; there was a rising trend of prevalence of gallstones in men with increasing age (p<0.05). A third of the patients (142 [34%]) were symptomatic. The mean duration of symptoms was 12.1 months. One hundred and ninety seven patients (48%), including 90 asymptomatic ones, underwent cholecystectomy. Most patients (92.5% of those symptomatic and 76.6% of those asymptomatic) underwent cholecystectomy within one year of diagnosis. Eight asymptomatic patients underwent surgery 3 years or more after diagnosis. The predominant color of stones retrieved was black or brown (57%) or mixed (39%). CONCLUSIONS: A majority of patients with gallstone disease had cholecystectomy within one year of diagnosis. Black or brown pigment stones were the dominant types of gallstones.     

Risk factors for symptomatic gallstones in patients with liver cirrhosis: a case-control study

OBJECTIVES: Liver cirrhosis is a well-documented risk factor for the formation of gallstones. In cirrhotic patients, gallstones are almost always "silent," and surgery is rarely required. When indicated (symptoms or complications), cholecystectomy implies a high morbidity risk in these patients, especially in the advanced stages of cirrhosis. The aim of this study was to estimate the risk factors for symptom development in cirrhotic patients with gallstones to identify the subgroup of patients at risk of undergoing surgery. METHODS: A total of 140 patients with liver cirrhosis and gallstones were studied: 97 with asymptomatic and 43 with symptomatic gallstone disease. The risk factors for gallstone formation (age, gender, family history, parity, obesity, diabetes mellitus, hyperlipoproteinemia) and the characteristics of liver cirrhosis (etiology, duration, Child class, hypersplenism), gallstones (duration, number, size), and gallbladder (size, wall thickness) were assessed in all patients. In 12 patients (four symptomatic, eight asymptomatic), gallbladder emptying was also evaluated by ultrasound. The association of asymptomatic and symptomatic gallstones with all these parameters was statistically evaluated by Student's t, Mann-Whitney, and chi(2) tests, as well as by means of multiple logistic regression. The causal relationship between these characteristics and gallstone symptoms was also examined by means of the KDD (knowledge discovery from databases) method, with an algorithm for learning Bayesian networks. RESULTS: Advanced age, female gender, viral etiology of cirrhosis, family history of gallstones, and duration of gallstone disease were significantly associated with symptomatic gallstone disease. The number or size of gallstones and the size or emptying of the gallbladder did not differ in symptomatic versus asymptomatic patients. Male gender and alcoholic cirrhosis were inversely correlated with symptom presence. In the multivariate analysis, family history (p = 0.0098) and advanced age (p = 0.0422) were positively correlated and male gender (p = 0.0049) and alcoholic etiology of cirrhosis (p = 0.0116) negatively correlated with symptom presence. These relationships (except for age) were also evidenced by the KDD method. CONCLUSIONS: The risk of gallstones becoming symptomatic is significantly lower in men and in alcoholic cirrhosis. In cirrhotic women, and especially in the presence of a positive family history and of advanced age, the risk of developing symptoms and undergoing surgery was significantly greater.     

Effect of NSAIDs on gallbladder bile composition

Secretion of gallbladder mucin is an important step in gallstone pathogenesis. Previous studies have demonstrated that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) can both inhibit gallbladder mucin secretion and prevent gallstone formation in animal models of cholesterol gallstone disease. The present study was performed to determine if chronic NSAID use was associated with a reduction in the mucin content or affected the lipid components of human gallbladder bile. Four groups of patients were identified retrospectively from a cohort of 230 morbidly obese patients who underwent gastric bypass surgery. The index group consisted of 18 patients who were found to have gallstones at gastric bypass surgery and had a history of chronic NSAID use. Three other patient groups were identified from the cohort by matching this index population for sex, race, and age according to the following criteria: (1) patients with gallstones who had not utilized NSAIDs, (2) patients without gallstones but with chronic NSAID use, and (3) patients without gallstones and without a history of NSAID use. Gallbladder bile was obtained from all patients by direct aspiration from the gallbladder at the time of surgery. Patients with gallstones had a significantly (P<0.02) greater concentration of gallbladder mucin in their gallbladder bile compared to patients without gallstones (0.897±0.226 vs 0.173±0.039 mg/ml). Among gallstone patients, gallbladder mucin was reduced in those patients with a history of chronic NSAID use (1.18±0.43 vs 0.74±0.19 mg/ml). Chronic NSAID use was also associated with a reduction in the cholesterol/phospholipid ratio of gallbladder bile in patients with and without gallstones. These data suggest that chronic NSAID use may later the mucin and lipid content of gallbladder bile in a manner that could reduce the risk for gallstone formation.Supported by NIH-FIRST award DK43264 (M.L.S.) and NIH grant DK47628 (E.W.M.) from the National Institutes of Digestive and Kidney Diseases.     

Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians

BACKGROUND & AIMS: Gallstone disease is an important, costly health-care problem in Western societies. It is still unclear whether hepatic lipid regulatory enzymes play primary or secondary roles in gallstone formation. In this study, the aim was to investigate whether the synthesis of bile acids and cholesterol is increased in gallstone disease and to test whether such a metabolic change, if present, might occur before gallstone formation. METHODS: A total of 125 Chilean Hispanic women (80 without gallstones and 45 with gallstones) matched for age and body mass index were investigated, along with 40 Chilean Mapuche Indian women (20 without gallstones and 20 with gallstones), a population group in which the prevalence for gallstone disease is very high. Fasting blood plasma samples were assayed for 7 alpha-hydroxy-4-cholesten-3-one and lathosterol, 2 strong indicators for hepatic bile acid and body cholesterol synthesis, respectively. RESULTS: Plasma 7 alpha-hydroxy-4-cholesten-3-one levels, corrected for plasma cholesterol, were significantly increased by 50% in Hispanic women with gallstones as compared with gallstone-free Hispanics (P < 0.006). As compared with Hispanic women without gallstones, plasma 7 alpha-hydroxy-4-cholesten-3-one levels were increased by > or =100% (P < 0.002) in Mapuche Indian women, independently of whether gallstones were present. Plasma lathosterol, corrected for plasma cholesterol, was significantly increased by 22% in Hispanic women with gallstones and in Mapuche Indian women compared with Hispanic women. CONCLUSIONS: The results indicate that the synthesis of bile acids and cholesterol is induced in gallstone disease and precedes gallstone development. These inductions presumably occur as a response to an increased intestinal loss of bile acids.     

Incidence of gallstone disease in Italy：Results from a multicenter,population-based Italian study （the MICOL project）

AIM：To evaluate gallstone incidence and risk factors in a large population-based study. METHODS： Gallstone incidence and risk factors, were evaluated by structured questionnaire and physical examination, respectively, in 9611 of 11 109 （86.5%） subjects who were gallstone-free at the cross-sectional study. RESULTS： Six centers throughout Italy enrolled 9611 subjects （5477 males, 4134 females, aged 30-79 years）, 9517 of whom were included into analysis： 424 subjects （4.4%） had gallstones and 61 （0.6%） had been cholecystectomized yielding a cumulative incidence of 0.67% per year （0.66% in males, 0.81% in females）. Increasing age, a high body mass index （BMI）, a history of diabetes, peptic ulcer and angina, and low cholesterol and high triglyceride levels were identifi ed as risk factors in men while, in females, the only risk factors were increasing age and a high BMI.Increasing age and pain in the right hypocondrium in men and increasing age in females were identifi ed as predictors of gallstones. Pain in the epigastrium/ right hypocondrium was the only symptom related to gallstones; furthermore, some characteristics of pain （forcing to rest, not relieved by bowel movements） were significantly associated with gallstones. No correlation was found between gallstone characteristics and clinical manifestations, while increasing age in men and increasing age and BMI in females were predictors of pain. CONCLUSION：Increasing age and BMI represent true risk factors for gallstone disease （GD）; pain in the right hypocondrium and/or epigastrium is confi rmed as the only symptom related to gallstones.     

Single-stage laparoscopic management of acute gallstone pancreatitis：outcomes at different timings

BACKGROUND:Definitive therapy for gallstone pancreatitis requires eradication of gallstones with cholecystectomy and common bile duct(CBD) clearance.Current guidelines recommend this be done within the same admission and preferably by laparoscopic cholecystectomy and CBD exploration.We report our experience of laparoscopic single-stage management with cholecystectomy and intraoperative cholangiogram followed by laparoscopic bile duct exploration(LBDE) when necessary performed at three different stages.METHODS:From January 1998 to December 2012,134 patients(100 females and 34 males) underwent single-stage laparoscopic management of gallstone pancreatitis.Patients were classified according to the timing of surgery:"A",≤7 days from symptom onset(n=27); "B",8 to 30 days(n=58) and "C",30 days(n=49).RESULTS:LBDE was performed in 30 patients with a success rate of 100%.CBD stones were found in 25 patients(A:22.2%,B:22.4%,C:12.2%).CBD stones were more common in patients undergoing surgery within 30 days of presentation than after this time point(P=0.35).Multiple choledocholithiasis was more frequent in patients treated within 7 days(P=0.04).The 30-day mortality after surgery was 0,with no conversion to an open approach.Overall complication rate was 11.9%,which did not differ significantly between patients treated within 7 days or after this time point(P=0.83).CONCLUSIONS:This study demonstrated the feasibility and reproducibility of single-stage laparoscopic management of acute gallstone pancreatitis,which has a low complication rate at any stage.Patients undergoing early treatment have a higher incidence of choledocholithiasis and multiple stones than those treated after 30 days,supporting the passage of stones with time.     

Gallstone disease prevalence in Western Siberia: cross-sectional ultrasound study versus autopsy

BACKGROUND: The aims of this study were: (i) to evaluate the prevalence of gallstones in a Western Siberian urban population; and (ii) to compare the results of ultrasonographic screening of the living population with hospital autopsy data. METHODS: A representative sample of 842 men and 870 women (aged 25-64 years) living in Novosibirsk, Western Siberia, was screened for the presence of gallstones by gallbladder ultrasonography. Participants were considered to have gallstone disease if they had already had cholecystectomy or if gallstones were revealed during the survey. Hospital autopsy data (n = 1124) were reviewed retrospectively for the 8-year period in the same region. RESULTS: The prevalence of gallstone disease was significantly higher in women than in men and increased with age. Age-adjusted prevalence rates of gallstone disease for the 25-64-year age group were 1.9% in men and 9.5% in women in a cross-sectional ultrasonographic study. Corresponding values in the autopsy series were 2.2% in men and 11.2% in women. CONCLUSIONS: The present report shows that the prevalence of gallstone disease in the female population is in the range of that reported from Western countries, whereas that in the male population is lower than that in other countries. The results of the ultrasonographic survey of the living population and of hospital autopsy data were comparable, with slightly higher gallstone detection rates in the autopsy study.     

Pathophysiological significance of gallbladder volume changes in gallstone diseases

AIM: To study the pathophysiological significance of gallbladder volume (GBV) and ejection fraction changes in gallstone patients.METHODS: The fasting GBV of gallstone patients with acute cholecystitis (n = 99), chronic cholecystitis (n = 85) and non-gallstone disease (n = 240) were measured by preoperative computed tomography. Direct saline injection measurements of GBV after cholecystectomy were also performed. The fasting and postprandial GBV of 65 patients with gallstones and chronic cholecystitis and 5...     

Prevalence of Gallstone Disease in a Swedish Population Sample: Relations to Occupation,Childbirth, Health Status,Life Style,Medications, and Blood Lipids

Background: There are only a few Swedish studies on the prevalence of gallstone disease in selected age groups, and none including possible risk factors. Methods: Of a population sample of 1200 individuals (age, 35-85 years), 857 participated in the study. The study subjects were asked to answer a questionnaire about potential risk factors (occupation, childbirth, life style, and so forth), symptoms, and quality of life. Cholecystectomy had previously been done in 115 subjects, leaving 742 for ultrasound examination of the gallbladder. Results: The prevalence of gallstone disease increased with age, and at 75 years or more, 53% of the women and 32% of the men either had gallstones or had previously undergone cholecystectomy (32% and 13%, respectively). When comparing subjects with and without gallstones, there were no differences with regard to any variable, including blood lipid levels. The odds ratio of previous cholecystectomy was increased in subjects with an occupation requiring no specific education and reduced in subjects using wine or spirits every week. The odds ratio of abdominal pain was increased after previous cholecystectomy. Women in this group also experienced a lower quality of life. Conclusions: The age and sex distribution of gallstone disease was in the order of the magnitude seen in other Scandinavian countries. None of the studied variables differed between subjects with and without gallstones. Subjects previously operated on with cholecystectomy did worse with regard to symptoms and quality of life.     

Small gallstones are associated with increased risk of acute pancreatitis: potential benefits of prophylactic cholecystectomy?

OBJECTIVES: Pancreatitis is a severe complication of gallstone disease with considerable mortality. Small gallstones may increase the risk of pancreatitis. Our aims were to evaluate potential association of small stones with pancreatitis and potential beneficial effects of prophylactic cholecystectomy. METHODS: Stone characteristics were determined in patients with biliary pancreatitis (115), obstructive jaundice due to gallstones (103), acute cholecystitis (79), or uncomplicated gallstone disease (231). Sizes and numbers of gallbladder and bile duct stones were determined by ultrasonography and endoscopic retrograde cholangiopancreatography, respectively. Effects of prophylactic cholecystectomy were assessed by decision analyses with a Markov model and Monte Carlo simulations. RESULTS: Patients with pancreatitis or obstructive jaundice had more and smaller gallbladder stones than those with acute cholecystitis or uncomplicated disease (diameters of smallest stones: 3 +/- 1, 4 +/- 1, 8 +/- 1, and 9 +/- 1 mm, respectively, p < 0.01). Bile duct stones were smaller in case of pancreatitis than in obstructive jaundice (diameters of smallest stones: 4 +/- 1 vs 8 +/- 1, p < 0.01). Multivariate analysis identified old age and small stones as independent risk factors for pancreatitis. Decision analysis in a representative group of patients with small (相似文献   

A population study on the prevalence of gallstone disease: the Sirmione Study

The prevalence of gallstone disease (cholelithiasis and previous cholecystectomy for gallstones) in the population of the town of Sirmione, Italy, examined by ultrasonography, was 6.7% in men and 14.6% in women, ranging from 18 to 65 yr of age (overall prevalence = 11%). The prevalence of cholelithiasis in the same age span was 6.9% (4.5% in men and 8.9% in women). Prevalence of cholelithiasis increased with age in both sexes. Twenty-two percent of gallstone subjects suffered from biliary pain vs. 2% of subjects without gallstones. No difference was observed in the frequency of nonspecific symptoms between subjects with and without gallstones. Of the 132 gallstone subjects, 108 (82%) were not aware of having gallstones prior to the study. Prevalence of gallstone disease was found to be higher in obese and hypertriglyceridemic subjects and to increase with the number of pregnancies.     

Clinical manifestations of gallstone disease: evidence from the multicenter Italian study on cholelithiasis (MICOL).

Despite the many efforts to delineate the clinical manifestations of gallbladder disease, the precise symptom complex associated with gallstones is still a matter of debate, and even the existence of gallstone-specific symptoms has been questioned. We carried out a large population-based cross-sectional study (MICOL) to identify symptoms significantly related to gallstones. Fourteen centers throughout Italy enrolled 29,504 subjects aged 30 to 69 years. All subjects were administered an ultrasonographic examination of the upper abdomen and a precoded questionnaire. All subjects were divided into 4 groups: 25,374 (86.0%) gallstone-free subjects (GF), 1,832 (6.2%) patients with gallstones not previously diagnosed (GNPD), 638 (2.2%) patients with gallstones previously diagnosed (GPD), 1,660 (5.6%) patients with a history of cholecystectomy for gallstones (CC). In logistic regression analysis, pain at epigastrium and, even more, pain at right hypocondrium were significantly associated with gallstones. For pain at right hypocondrium, this association progressively increased from GNPD (OR = 1.60, 95% CI = 0.97-2.65) to GPD (OR = 8.77, 95% CI = 5.27-14.61) to CC (OR = 59.40, 95% CI = 43.87-80.42). Absence of heartburn combined with right hypocondrium or epigastrium pain and intolerance to fried or fatty food were also significantly related to gallstones. We also found some pain characteristics significantly associated with gallstones, i.e., pain radiated to the right shoulder, forcing the patient to rest, occurring soon after meals or unrelated to meals, not relieved by bowel movements, and frequently accompanied by gallstone-related morbidities. We developed a probability tree reporting the cumulative probability of having gallstones for each combination of those symptoms and characteristics of pain significantly associated with gallstones. In conclusion, we have identified symptoms and signs significantly associated with gallstones. We have shown that there is an increase in frequency and severity of these symptoms and signs across the different stages of gallstone disease. We have proposed a complex of symptoms and signs significantly associated with gallstones that might help physicians in clinical decision making.     

Distribution of cholesterol between vesicles and micelles in human gallbladder bile: influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid

The present study aimed at determining the relative distribution of cholesterol between the vesicular and micellar phases in gallbladder bile of gallstone patients (n = 23) and gallstone-free subjects (n = 7). Nine of the gallstone patients were treated with chenodeoxycholic acid and seven were treated with ursodeoxycholic acid, 15 mg/kg/day, for 3 wk before cholecystectomy. The vesicular and micellar fractions in bile were separated by sucrose density gradient ultracentrifugation, and a clear separation between the two phases was obtained. The vesicles were further identified by quasielastic light scattering spectroscopy and appeared to be of a uniform size with a mean hydrodynamic radius of 760 A. The proportion of cholesterol in the vesicular fraction was significantly higher in the untreated gallstone group (40% +/- 4%) compared with the gallstone-free (28% +/- 3%), ursodeoxycholic acid (28% +/- 3%) and chenodeoxycholic acid (18% +/- 4%) groups. Despite a low cholesterol saturation of bile in the latter three groups (88% +/- 12%, 51% +/- 9% and 65% +/- 5%, respectively), a considerable part of the biliary cholesterol was carried in the vesicular fraction. The cholesterol/phospholipid ratio in the vesicular fraction averaged between 0.49 and 0.58 in the gallstone, gallstone-free and chenodeoxycholic acid groups, whereas the ursodeoxycholic acid group had a significantly lower ratio of 0.24. The nucleation time of bile from the gallstone group was short (2 +/- 1 days) compared with the gallstone-free, chenodeoxycholic acid and ursodeoxycholic acid groups (23 +/- 3, 24 +/- 6 and 14 +/- 3 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence of cholesterol gallstones positively correlates with per capita daily calorie intake

BACKGROUND/AIMS: Gallstone composition has changed over the past decades in East Asian countries with a prominent increase in the prevalence of cholesterol gallstones. This trend is possibly due to the westernization of dietary habits. This study was undertaken to delineate the changing trends in gallstone composition in Japan since the 1920s and to assess dietary influences on gallstone composition. METHODOLOGY: Between 1971 and 1999, 1264 Japanese patients underwent cholecystectomy for gallstone disease in Niigata University Medical Hospital. Gallbladder stones retrieved from each patient were classified into four types by gross inspection of the cut surface and infrared spectroscopy: cholesterol stone, black pigment stone, brown pigment stone, and other stones. The literature was reviewed to find both changing trends in gallstone composition before 1971 and dietary changes since 1950 in Japan. RESULTS: The prevalence of cholesterol gallstones among Japanese patients undergoing cholecystectomy increased steadily until the 1970s and declined thereafter (P<0.001). Among dietary factors, only per capita daily total calorie intake strongly correlated with cholesterol gallstone prevalence (r=0.93, P=0.02). CONCLUSIONS: During the 20th century, the prevalence of cholesterol gallstones in the Japanese population increased steadily until the 1970s declining thereafter. Per capita daily total calorie intake appears to be the predominant dietary factor affecting cholesterol gallstone prevalence.     

Cholesterol metabolism in human gallbladder mucosa: relationship to cholesterol gallstone disease and effects of chenodeoxycholic acid and ursodeoxycholic acid treatment.

The objective of this study was to investigate cholesterol metabolism in human gallbladder mucosa, especially in relation to hepatic cholesterol metabolism, gallstone disease and treatment with bile acids. Gallbladder mucosa and liver tissue samples were collected in 44 patients undergoing cholecystectomy; 30 had cholesterol gallstones and the rest were stone free. Ten of the gallstone patients were treated with chenodeoxycholic acid and eight received ursodeoxycholic acid, with a daily dose of 15 mg/kg body wt, for 3 wk before surgery. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, governing cholesterol synthesis, was considerably lower in the gallbladder mucosa than in liver tissue (28 +/- 6 and 120 +/- 40 pmol/min/mg protein). The acyl coenzyme A:acyltransferase activity in the gallbladder mucosa catalyzing the esterification of cholesterol was, on the other hand, several times higher than corresponding activity in the liver (92 +/- 23 and 11 +/- 2 pmol/min/mg protein). In the presence of exogenous cholesterol, the acyl coenzyme A:acyltransferase activity increased about twofold in the gallbladder mucosa. The acyl coenzyme A:acyltransferase activity of the gallbladder mucosa from untreated gallstone patients was not stimulated further by the addition of exogenous cholesterol. Otherwise, there were no significant differences in acyl coenzyme A:acyltransferase and 3-hydroxy-3-methylglutaryl coenzyme A reductase activities in the gallbladder mucosa of gallstone patients compared with gallstone-free controls. Treatment with chenodeoxycholic and ursodeoxycholic acids did not affect the 3-hydroxy-3-methylglutaryl coenzyme A reductase activity of the gallbladder mucosa but reduced the acyl coenzyme A:acyltransferase activity by 60% to 65%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lysosomal enzyme activities in gallbladder mucosa of gallstone-free subjects and patients with gallstones

Background/Aims: Gallstone patients have a reduced cellular lysosome content in the gallbladder mucosa cells compared with gallstone-free subjects. The purpose of the study was to further evaluate the possible role of lysosomes in the pathogenesis of cholesterol gallstone formation in humans.Methods: Lysosomal enzyme activities were assayed in gallbladder mucosa and for comparison in liver specimens of 19 gallstone-free subjects and 24 gallstone patients undergoing cholecystectomy.Results: Gallstone patients had 25–50% lower activities of the lysosomal proteases cathepsin B, D and L in their gallbladder mucosa compared with gallstone-free subjects. The activity of acid phosphatase also tended to be decreased in gallstone patients. The liver lysosomal enzyme activities were not significantly different between the two groups.Conclusions: The results show that gallstone patients have diminished lysosomal enzyme activities in the gallbladder mucosa, a finding which may be related to decreased intracellular degradation of proteins and/or mucin in the mucosal cells. This may lead to a higher concentration of mucin in gallbladder bile and thus an increased risk of precipitation of cholesterol crystals and gallstone formation.