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Obesity and gallstones: Is dietary behaviour a risk factor?
H E P A T O L O G Y V o l . 22, N o . 4, P t .
2, 1 9 9 5
AASLD
2 5 GALLSTONE RECURRENCE AFTER SUCCESSFUL ORAL BILE ACID TREATMENT: A 20 YEAR FOLLOW-UP EVALUATION.
ABSTRACTS
26
FREQUENCY AND CHARACTERISTICS OF ABDOMINAL SYMPTOMS IN GALLSTONE DISEASE: RESULTS OF AN EPIDEMIOLOGICAL STUDY
D.Festi*, A.Sangermano, S.Sottili, A.Colecchia, M Orsini, E.Roda and the M.I.COL. Group. *Pbysiopathology Department, University G.D'Annunzio, Chieti end Gastroenterology Department, Universityof Bologna, llaly. Different surgical and non surgical therapeutic options are presently available for the menagementof gallstone patients. One of the key factors in clinical decision making is the recognition of symptoms caused by the gallstones; however, there is still no definitive agreementregardingthe abdominalsymptomsapeeifieallyattributable this condition. The aim of the present study was to evaluate the frequencyend characteristicsof abdominal symptoms in gallstone disease (GD) patients, during an epideminlogieal study, Multicentrica Italiena Colelitiasi (M.I.COL.),a community-basedinvestigationof GD prevalencein Italy, involving lg cohorts in l0 Italian regions. Components of the study protocol pertinent to this work include uttrasonographic (US) examination of the upper abdomen end direct interview of subjects using a preceded questionnaire regardingmedical history end abdominalsymptoms during the 5 years prior to the interviewin normals (N) end in gallstone patients (G), end in the 5 yrs prior to surgery in eholecysteetomizedpatients (C). The population studied comprised 29,584 subjects ( 15,910 male~end 13,674 females;aged 30-69 yrs). On the basis of the clinical end US results, this population was divided into the following groups: N= 25479, G=2480 end C=1634. The frequency of abdominal symptoms (belching, heartburn, nausea, vomiting,bloated feeling after meals, intoleranceto fatty or fried foods, heavy feeling on the right side or epigastrium, bitter taste in the morning end abdominal pain) and the characteristics of pain (localization, radiation, intensity, frequency,relation to meal, rate of complications) when present, were evaluated on the basis of the questionnaire. Multivariate analysis was performedwith the multiple logistic regressionmodel to estimatethe Odds Ratio and the 95% C.L. adjusted for the other variables in the model. Multivariate analysis demonstrated that, among the evaluated symptoms, three were elusely linked to gallstone disease: abdominalpain (OR 2.2 G vs N; OR 4.4 C vs N), heavy feelingon the right side ( OR 1.3 G vs N; OR 1.7 C vs N) end intoleranceto fatty or fried foods ( OR 1.2 G vs N; OR 1.3 C vs N). Pain was present in 17.9% of G, 72.5% of C prior to surgery end 8.3% of N. With respect to N, the pain in G tends to radiate (OR 1.3), is variable in duration, forcesthe patient to lie down (OR 1.3), is not relieved by bowel movements(OR 1.2), is meal-related end triggered by abundant meals (OR 1.2), and can be associated with complications(OR 1.4). In C before surgery, with respect to N, the pain forces the patient to lie down (OR 2.2), needs drugs to be relieved (OR 1.3), h~ a longer duration (OR 1.3), occurs more frequently (OR 1.5), is meal-related (OR 1.2), is not relieved by bowel movements(OR 1.6), and is more frequently associatedwith complications(OR 2.1). This study confirmsthat abdominal pain is closely aseneiatedwith gallstone disease, end also shows that other abdominalsymptomsare significantly linked to this disorder. If confirmed by the longitudinal study, these findings could be useful in the therapeuticmanagementof gallstene patients.
OBESITY AND GALLSTONES: IS DIETARY BEHAVIOURA RISK FACTOR?
N.Villanova D.Festi*, S.Sottili, G.Mazzella, S.Geminiani~ A.Puccetti, M. Orsini, A.Sangermano, E.Roda Gastroenterology Department, University of Bologna, Italy *Physiopathology Department, University G.D'Annunzio, Chieti, Italy
The Bologna Gronp: F Bazzoli~ D Festi, G Mazzella, MR Zagari, S Fossi. P Pozzato M Orsini, A Sangermano, A Cipolla, P Simoni, A Roda and E Redo. Cattedra di Gastroenterologia, Universita' di Bologna, Italy. An initial cohort of 86 subjects (Gastroenterology 1989;97:727-31) has been followed for 20 years after oral bile acid gallstone dissolution. Yearly ultrasound and clinical evaluation have been carried out in all subjects. In addition, at this 20th annual follow-up evaluation, ultrasound studies of gallbladder motility were performed and the cholesterol saturation index calculated (by conventional anal)~ical methods in stimulated duodenal bile) in 21 subjects, 11 with and 10 without gallstone recurrence. Nucleation time was determined in bile samples obtained by endoscopic bile duct canulaiion from 7 subjects, 4 with and 3 without recnrrence. The recurrence rate, calculated by tile actuarial thethod, was 61% during the first 10 years, but no 51rlher cases were detected during the subsequent 10 years of follow-up. Of the subjects with reeorrent gallstones these presented with biliary colic in only 24.5%. bet were asa'mptomalic 31 the time of detection, and hm'e remained so in 75.5%. Studies of g,ailbladder motility showed that basal vohanes were similar in subjects with and withoul gallstones recurrence while residual vohlmes were significantly (p<0.05) grealer in snbjccls with recurrence (g.9+1.2 ml) than in lhose without (5.7_+0.7 ml). Also. the percent emp!ying w:~s significantly reduced in the former (57.5% 5:7.1 vs 73.1°/~++3.1; p<0.05). The cholesterol saturation index was significantly (p<0.02) higher in subjects with recurrence (i.5_+0.2) than in those withonl (0,9-~.1). Biliary bile acid composition was characterized by a significantly greater (p<0.01) concentralion of dcoxa'cl~olic acid in subjects ~Sth (21%+2) than in stthjects without recurrence (14%+1). Nucleation time was faster in subjec!s with (1-7 days) than in stlbjec!s withont recurrence (> 21 days). CONCLUSIONS:gallstone patients successfidly treated with oral bile acid dissolution therapy are prone to recnrrcnce, however the great majority remains asymptomatic. A recurrence free period of, at most, 10 years clearly discriminates patients who are not going to develop recurrent gallstones and wile can thus be considered cured. In further support of this assertion, the triple defect of biliary cholesterol snpersaturation, abnormal nucleation and gallbladder dismotility is absent in these sobjecls, whereas il persists in lhese with recurrence.
27
l13A
Obese patients are at high risk for cholesterol gallstone formation. The effect of dieting on gallstone formation in obese patients is still debated. Aim of our study was to evaluate dietary behaviour in a group of obese patients admitted in our hospital for bariatric surgery. We studied 215 female obese patients (mean age 36.9±0.7, yrs~SE, age range 16-71 yrs old), BMI 45.8±7.3 (kg/m2±SE), range 30-82. 161 were gallstone free, 30 had gallstones (US and/or radiological confirmed stones) 24 were eholecistectomized. A detailed semistructured questionnaire was administered, in order to assess dieting, weight cycling, eating attitudes, putative risk factors for gallstones and medical history. All patients underwent a 7-day dietary recall for caloric intake analysis. Results: Gallstone patients (G) were older than gallstone free patients (GF) (41.1±I .8 vs 36.2"1, M (yrs)~SE, respectively, p<0.05); BMI differed significantly in the two groups (GF: 45.5±0.6, G: 48.2±I.1, kg/m~±SE, p<0.05); dieting, maximal weight loss during a single diet and total weight loss during all diets were significantly different: (number of diets: 3.7±0.2 vs 5.2~0.5 (no. of " dietszt:SE), GF vs G, M~-SE, p<0.01; maximal weight loss: 22.9~0.9 vs 27.1±2.2 (Kg'~SE), GF vs G, p<0.04; total weight loss: 49.4±2.4 vs 68.3-~6.5,(average in kg lost~SE), GF vs G, p<0.01); G had a reduced meal number in the day, particularly they had no breakfast when compared to GF (G who have not breakfast/G with breakfast (%): 18/36 (33.3%); GF who have not breakfastJGF with breakfast (%): 30/131 (18.6%), G vs GF, p<0.05). No differences between the two groups were found in total energy intake, food selection, parity and other putative risk factors for gallstone disease. Conclusions: our data confirm that higher BMI is positively associated with higher risk of gallstone disease. Frequent dieting, weight cycling and eating attitudes, particularly not having brakfast with a prolonged night fast, may increase the risk of developing gallstones.
28
META-ANALYSIS O F I N T E R F E R O N R A N D O M I Z E D TRLALS IN T H E T R E A T M E N T OF VIRAL H E P A T I T I S C. E F F E C T S OF DOSE AND DURATION. T Po~inard 1-2, V Leroy3LM Cohard 3, P Mathutinl. P Opolon 1, JP Zars~ 3. 1Service d'Hrpato-Gastroenterologie, Groupe Hospitalier Pitir-Salp&ri~re, 1-2CNRS URA 1484, Paris, 3H~pital Michallon, Grenoble. The aim of this overview was to assess the efficacy of a standard interferon regimen (3 MIU TIW for 6 months) in chrome hepatitis C in terms of A L T complete and sustained responses and liver histological improvement, as well as to evaluate the benefit of higher doses or longer duration and to assess the efficacy ofinterfaron in acute hepatitis C. Methods: All randomized trials with interferon in chronic hepatitis C, using doses greater than or equal to 3 MIU TIW for at least 6 months in previously non-treated patie~ats and in patients with acute hepatitis C, were considered for inclusion. Meta-analysis made use of the Pete et al and the Der Simonian and Laird methods, with heterogeneity and sensitivity analyses according to type of publication , medaodological quality, prevalence of cirrhosis and type of interferon. Results: In chrome hepatitis, a total of 20 trials versus controls and 17 trials comparing different interferon regimens were included. Standard regimen, that is 3 MIU TIW for 6 months, increased the complete and sustained ALT response rate by 49% and 20% respectively, with the natural course being less than 1% of spontaneous responses. The dose effect (6 vs 3 MIU) upon the complete ALT response rate at the end oftreatmertt was significant and homogeneous, with a mean of 10% improvement at both 6 and 12 months. At 6 months there was no sigmficant dose effect upon the ALT sustained response. There was a si~aificant dose effect (6 vs 3 MIU TIW) at 12 months, with a mean 17% increase in t h e sustained response rate. There was a significant duration effect upon the sustained response rate both at 3 and at 6 MIU T1W, with a mean of 17%(at least 12 vs 6 months). In acute hepatitis C, 3 months interferon treatment showed significant efllcacy versus controls, both upon the complete ALT response (73 vs 35%,p<0.001) and the sustained response rate during the 12 months following treatment (60 vs 33%,p=0.003). Conclusions: The best etficaey/risk ratio was in favor of 3 MIU TIW for at least 12 months in patients with chronic hepatitis C who had never beea treated by interferon. Patients with acute hepatitis should be treated with at least 3 MI'U TIW for 3 months.
2, 1 9 9 5
AASLD
2 5 GALLSTONE RECURRENCE AFTER SUCCESSFUL ORAL BILE ACID TREATMENT: A 20 YEAR FOLLOW-UP EVALUATION.
ABSTRACTS
26
FREQUENCY AND CHARACTERISTICS OF ABDOMINAL SYMPTOMS IN GALLSTONE DISEASE: RESULTS OF AN EPIDEMIOLOGICAL STUDY
D.Festi*, A.Sangermano, S.Sottili, A.Colecchia, M Orsini, E.Roda and the M.I.COL. Group. *Pbysiopathology Department, University G.D'Annunzio, Chieti end Gastroenterology Department, Universityof Bologna, llaly. Different surgical and non surgical therapeutic options are presently available for the menagementof gallstone patients. One of the key factors in clinical decision making is the recognition of symptoms caused by the gallstones; however, there is still no definitive agreementregardingthe abdominalsymptomsapeeifieallyattributable this condition. The aim of the present study was to evaluate the frequencyend characteristicsof abdominal symptoms in gallstone disease (GD) patients, during an epideminlogieal study, Multicentrica Italiena Colelitiasi (M.I.COL.),a community-basedinvestigationof GD prevalencein Italy, involving lg cohorts in l0 Italian regions. Components of the study protocol pertinent to this work include uttrasonographic (US) examination of the upper abdomen end direct interview of subjects using a preceded questionnaire regardingmedical history end abdominalsymptoms during the 5 years prior to the interviewin normals (N) end in gallstone patients (G), end in the 5 yrs prior to surgery in eholecysteetomizedpatients (C). The population studied comprised 29,584 subjects ( 15,910 male~end 13,674 females;aged 30-69 yrs). On the basis of the clinical end US results, this population was divided into the following groups: N= 25479, G=2480 end C=1634. The frequency of abdominal symptoms (belching, heartburn, nausea, vomiting,bloated feeling after meals, intoleranceto fatty or fried foods, heavy feeling on the right side or epigastrium, bitter taste in the morning end abdominal pain) and the characteristics of pain (localization, radiation, intensity, frequency,relation to meal, rate of complications) when present, were evaluated on the basis of the questionnaire. Multivariate analysis was performedwith the multiple logistic regressionmodel to estimatethe Odds Ratio and the 95% C.L. adjusted for the other variables in the model. Multivariate analysis demonstrated that, among the evaluated symptoms, three were elusely linked to gallstone disease: abdominalpain (OR 2.2 G vs N; OR 4.4 C vs N), heavy feelingon the right side ( OR 1.3 G vs N; OR 1.7 C vs N) end intoleranceto fatty or fried foods ( OR 1.2 G vs N; OR 1.3 C vs N). Pain was present in 17.9% of G, 72.5% of C prior to surgery end 8.3% of N. With respect to N, the pain in G tends to radiate (OR 1.3), is variable in duration, forcesthe patient to lie down (OR 1.3), is not relieved by bowel movements(OR 1.2), is meal-related end triggered by abundant meals (OR 1.2), and can be associated with complications(OR 1.4). In C before surgery, with respect to N, the pain forces the patient to lie down (OR 2.2), needs drugs to be relieved (OR 1.3), h~ a longer duration (OR 1.3), occurs more frequently (OR 1.5), is meal-related (OR 1.2), is not relieved by bowel movements(OR 1.6), and is more frequently associatedwith complications(OR 2.1). This study confirmsthat abdominal pain is closely aseneiatedwith gallstone disease, end also shows that other abdominalsymptomsare significantly linked to this disorder. If confirmed by the longitudinal study, these findings could be useful in the therapeuticmanagementof gallstene patients.
OBESITY AND GALLSTONES: IS DIETARY BEHAVIOURA RISK FACTOR?
N.Villanova D.Festi*, S.Sottili, G.Mazzella, S.Geminiani~ A.Puccetti, M. Orsini, A.Sangermano, E.Roda Gastroenterology Department, University of Bologna, Italy *Physiopathology Department, University G.D'Annunzio, Chieti, Italy
The Bologna Gronp: F Bazzoli~ D Festi, G Mazzella, MR Zagari, S Fossi. P Pozzato M Orsini, A Sangermano, A Cipolla, P Simoni, A Roda and E Redo. Cattedra di Gastroenterologia, Universita' di Bologna, Italy. An initial cohort of 86 subjects (Gastroenterology 1989;97:727-31) has been followed for 20 years after oral bile acid gallstone dissolution. Yearly ultrasound and clinical evaluation have been carried out in all subjects. In addition, at this 20th annual follow-up evaluation, ultrasound studies of gallbladder motility were performed and the cholesterol saturation index calculated (by conventional anal)~ical methods in stimulated duodenal bile) in 21 subjects, 11 with and 10 without gallstone recurrence. Nucleation time was determined in bile samples obtained by endoscopic bile duct canulaiion from 7 subjects, 4 with and 3 without recnrrence. The recurrence rate, calculated by tile actuarial thethod, was 61% during the first 10 years, but no 51rlher cases were detected during the subsequent 10 years of follow-up. Of the subjects with reeorrent gallstones these presented with biliary colic in only 24.5%. bet were asa'mptomalic 31 the time of detection, and hm'e remained so in 75.5%. Studies of g,ailbladder motility showed that basal vohanes were similar in subjects with and withoul gallstones recurrence while residual vohlmes were significantly (p<0.05) grealer in snbjccls with recurrence (g.9+1.2 ml) than in lhose without (5.7_+0.7 ml). Also. the percent emp!ying w:~s significantly reduced in the former (57.5% 5:7.1 vs 73.1°/~++3.1; p<0.05). The cholesterol saturation index was significantly (p<0.02) higher in subjects with recurrence (i.5_+0.2) than in those withonl (0,9-~.1). Biliary bile acid composition was characterized by a significantly greater (p<0.01) concentralion of dcoxa'cl~olic acid in subjects ~Sth (21%+2) than in stthjects without recurrence (14%+1). Nucleation time was faster in subjec!s with (1-7 days) than in stlbjec!s withont recurrence (> 21 days). CONCLUSIONS:gallstone patients successfidly treated with oral bile acid dissolution therapy are prone to recnrrcnce, however the great majority remains asymptomatic. A recurrence free period of, at most, 10 years clearly discriminates patients who are not going to develop recurrent gallstones and wile can thus be considered cured. In further support of this assertion, the triple defect of biliary cholesterol snpersaturation, abnormal nucleation and gallbladder dismotility is absent in these sobjecls, whereas il persists in lhese with recurrence.
27
l13A
Obese patients are at high risk for cholesterol gallstone formation. The effect of dieting on gallstone formation in obese patients is still debated. Aim of our study was to evaluate dietary behaviour in a group of obese patients admitted in our hospital for bariatric surgery. We studied 215 female obese patients (mean age 36.9±0.7, yrs~SE, age range 16-71 yrs old), BMI 45.8±7.3 (kg/m2±SE), range 30-82. 161 were gallstone free, 30 had gallstones (US and/or radiological confirmed stones) 24 were eholecistectomized. A detailed semistructured questionnaire was administered, in order to assess dieting, weight cycling, eating attitudes, putative risk factors for gallstones and medical history. All patients underwent a 7-day dietary recall for caloric intake analysis. Results: Gallstone patients (G) were older than gallstone free patients (GF) (41.1±I .8 vs 36.2"1, M (yrs)~SE, respectively, p<0.05); BMI differed significantly in the two groups (GF: 45.5±0.6, G: 48.2±I.1, kg/m~±SE, p<0.05); dieting, maximal weight loss during a single diet and total weight loss during all diets were significantly different: (number of diets: 3.7±0.2 vs 5.2~0.5 (no. of " dietszt:SE), GF vs G, M~-SE, p<0.01; maximal weight loss: 22.9~0.9 vs 27.1±2.2 (Kg'~SE), GF vs G, p<0.04; total weight loss: 49.4±2.4 vs 68.3-~6.5,(average in kg lost~SE), GF vs G, p<0.01); G had a reduced meal number in the day, particularly they had no breakfast when compared to GF (G who have not breakfast/G with breakfast (%): 18/36 (33.3%); GF who have not breakfastJGF with breakfast (%): 30/131 (18.6%), G vs GF, p<0.05). No differences between the two groups were found in total energy intake, food selection, parity and other putative risk factors for gallstone disease. Conclusions: our data confirm that higher BMI is positively associated with higher risk of gallstone disease. Frequent dieting, weight cycling and eating attitudes, particularly not having brakfast with a prolonged night fast, may increase the risk of developing gallstones.
28
META-ANALYSIS O F I N T E R F E R O N R A N D O M I Z E D TRLALS IN T H E T R E A T M E N T OF VIRAL H E P A T I T I S C. E F F E C T S OF DOSE AND DURATION. T Po~inard 1-2, V Leroy3LM Cohard 3, P Mathutinl. P Opolon 1, JP Zars~ 3. 1Service d'Hrpato-Gastroenterologie, Groupe Hospitalier Pitir-Salp&ri~re, 1-2CNRS URA 1484, Paris, 3H~pital Michallon, Grenoble. The aim of this overview was to assess the efficacy of a standard interferon regimen (3 MIU TIW for 6 months) in chrome hepatitis C in terms of A L T complete and sustained responses and liver histological improvement, as well as to evaluate the benefit of higher doses or longer duration and to assess the efficacy ofinterfaron in acute hepatitis C. Methods: All randomized trials with interferon in chronic hepatitis C, using doses greater than or equal to 3 MIU TIW for at least 6 months in previously non-treated patie~ats and in patients with acute hepatitis C, were considered for inclusion. Meta-analysis made use of the Pete et al and the Der Simonian and Laird methods, with heterogeneity and sensitivity analyses according to type of publication , medaodological quality, prevalence of cirrhosis and type of interferon. Results: In chrome hepatitis, a total of 20 trials versus controls and 17 trials comparing different interferon regimens were included. Standard regimen, that is 3 MIU TIW for 6 months, increased the complete and sustained ALT response rate by 49% and 20% respectively, with the natural course being less than 1% of spontaneous responses. The dose effect (6 vs 3 MIU) upon the complete ALT response rate at the end oftreatmertt was significant and homogeneous, with a mean of 10% improvement at both 6 and 12 months. At 6 months there was no sigmficant dose effect upon the ALT sustained response. There was a si~aificant dose effect (6 vs 3 MIU TIW) at 12 months, with a mean 17% increase in t h e sustained response rate. There was a significant duration effect upon the sustained response rate both at 3 and at 6 MIU T1W, with a mean of 17%(at least 12 vs 6 months). In acute hepatitis C, 3 months interferon treatment showed significant efllcacy versus controls, both upon the complete ALT response (73 vs 35%,p<0.001) and the sustained response rate during the 12 months following treatment (60 vs 33%,p=0.003). Conclusions: The best etficaey/risk ratio was in favor of 3 MIU TIW for at least 12 months in patients with chronic hepatitis C who had never beea treated by interferon. Patients with acute hepatitis should be treated with at least 3 MI'U TIW for 3 months.