Presentation is loading. Please wait.

Presentation is loading. Please wait.

Ursodeoxycholzuur bij Galsteenlijden Delft, 26.1.2010 U. Beuers Afdeling Maag-, Darm- en Leverziekten Academisch Medisch Centrum Universiteit van Amsterdam.

Similar presentations


Presentation on theme: "Ursodeoxycholzuur bij Galsteenlijden Delft, 26.1.2010 U. Beuers Afdeling Maag-, Darm- en Leverziekten Academisch Medisch Centrum Universiteit van Amsterdam."— Presentation transcript:

1 Ursodeoxycholzuur bij Galsteenlijden Delft, U. Beuers Afdeling Maag-, Darm- en Leverziekten Academisch Medisch Centrum Universiteit van Amsterdam

2 Bile Acid Treatment of Gallstone Disease - Historical Aspects M Schiff Suggestion to treat gallstone disease with bile acids 1876WC DabneyTreatment of gallstone disease with bile acids 1937AG Rewbridge“The disappearance of gallstone shadows following the prolonged administration of bile salts“ 1972 RG Danzinger et al.Dissolution of cholesterol gallstones by chenodeoxycholic acid 1975 I Makino et al.Dissolution of cholesterol gallstones by ursodeoxycholic acid L‘Imparziale 1873;13:97 Surgery 1937;1:395 N Engl J Med 1972;286:1 Jpn J Gastroenterol 1974;72:690 Am J Med Sci 1876;71:410

3  Which patient ?  Which stone ?  Which problems ? Ursodeoxycholic Acid in Gallstone Disease - Therapeutic Use -

4 Stages of Gallstone Disease Asymptomatic 18.5 % in women, 9.5 % in men * * Attili et al., Am J Epidemiol 1995;141:158

5 Stages of Gallstone Disease Asymptomatic Symptomatic Abdominal pain in the epigastrium or RUQ lasting for > 15 min ** ~20 % 18.5 % in women, 9.5 % in men * * Attili et al., Am J Epidemiol 1995;141:158 ** GREPCO, Dig Dis Sci 1987;32:349

6 Stages of Gallstone Disease Asymptomatic Symptomatic Complicated Abdominal pain in the epigastrium or RUQ lasting for > 15 min ** 1-2 % per year Acute cholecystitis, choledocho- lithiasis, pancreatitis, gallbladder cancer, gallstone ileus 18.5 % in women, 9.5 % in men * * Attili et al., Am J Epidemiol 1995;141:158 ** GREPCO, Dig Dis Sci 1987;32:349 ~20 %

7 Management of Gallstone Disease Asymptomatic Symptomatic Complicated No treatment (except stones > 3 cm, porcelain gallbladder)

8 Management of Gallstone Disease Asymptomatic Symptomatic Complicated Laparoscopic (or open) cholecystectomy or Nonsurgical treatment No treatment (except stones > 3 cm, porcelain gallbladder)

9 Management of Gallstone Disease Asymptomatic Symptomatic Complicated Laparoscopic (or open) cholecystectomy or Nonsurgical treatment Acute intervention No treatment (except stones > 3 cm, porcelain gallbladder)

10  Which patient ?  Which stone ?  Which problems ? Ursodeoxycholic Acid in Gallstone Disease - Therapeutic Use -

11 Gallstones Belitz & Braun, 1796Anatom. Museum Friedrich August Walter, Berlin

12 Cholesterol Gallstone Rettenmaier

13 Pathogenesis of Cholesterol Gallstone Disease Gallbladder hypomotility Super- saturation of bile Rapid nucleation

14 Effect of Bile Acid Therapy on Bile Lithogenicity Sharma et al., Gastroenterology 1998; 115: 124 Phospholipids (mmol/L) Bile salts (mmol/L) Cholesterol Saturation Index Cholesterol (mmol/L) 24.6 ± ± ± ± 2.1 Before UDCA 29.4 ± ± ± ± 2.4 After 8 weeks of UDCA NS p

15 Effects of UDCA on Cholesterol Gallstone Disease Gallbladder hypomotility Super- saturation of bile Rapid nucleation

16 Effect of UDCA on Bile Lithogenicity Sharma et al., Gastroenterology 1998; 115: 124 Nucleation time (days)8.5 ± 1.5 Before UDCA 19.0 ± 1.7 After 8 weeks of UDCA p

17 Effects of UDCA on Cholesterol Gallstone Disease Gallbladder hypomotility Super- saturation of bile Rapid nucleation

18 Effect of UDCA on Gallbladder Muscle Contractility Guarino et al., Gut 2007;56:815 After 4 weeks of Placebo After 4 weeks of UDCA

19 Effects of UDCA on Cholesterol Gallstone Disease Gallbladder hypomotility Super- saturation of bile Rapid nucleation

20  Which patient ?  Which stone ?  Which problems ? Ursodeoxycholic Acid in Gallstone Disease - Therapeutic Use -

21 Kinetics of in vitro Gallstone Dissolution by UDCA Senior et al., Gastroenterology 1990;99:249 Treatment time [month] Diameter [mm] Weight [mg] Weight % Diameter

22 Gallstone Recurrence after Bile Acid Dissolution Therapy Villanova et al., Gastroenterology 1989;97:727 Subjects at risk TIME FROM DISSOLUTION (yr) % RECURRENCE RATE

23  Stage of disease:symptomatic  Stone:< 5mm (optimal), 6-10 mm (acceptable) radiolucent (CT: iso-/hypodense to bile)  Gallbladder:patency of cystic duct and emptying after test meal (ultrasound) Selection Criteria for Ursodeoxycholic Acid Dissolution Therapy Paumgartner. In: Sleizenger & Fordtran‘ Gastrointestinal and Liver Diseases, 2002:1107

24  Stage of disease:symptomatic  Stone:< 5mm (optimal), 6-10 mm (acceptable) radiolucent (CT: iso-/hypodense to bile)  Gallbladder:patency of cystic duct and emptying after test meal (ultrasound) Optimal Acceptable 12% 3% Patients with gallstone disease qualified for UDCA treatment Paumgartner. In: Sleizenger & Fordtran‘ Gastrointestinal and Liver Diseases, 2002:1107 Selection Criteria for Ursodeoxycholic Acid Dissolution Therapy

25  Biliary colic ?  Stone formation ? Protection against: Ursodeoxycholic Acid in Gallstone Disease - Prophylactic Use -

26 Ursodeoxycholic Acid Reduces Long-term Risk of Biliary Colic in Gallstone Disease Tomida et al., Hepatology 1999;30: 9 A: symptomatic, no therapy B: symptomatic, UDCA C: asymptomatic, no therapy D: asymptomatic, UDCA Patients at risk A B C D A : P<0.001 B D C : P< Time (years) Cumulative Probability of Biliary Colic (%)

27 Ursodeoxycholic Acid Does not Reduce Short-term Risk of Biliary Colic in Gallstone Disease Venneman et al., Hepatology 2006;43:1276

28  Biliary colic ?  Stone formation ? Protection against: Ursodeoxycholic Acid in Gallstone Disease - Prophylactic Use -

29 Strong Risk Factors for Gallstone Formation  Rapid weight loss  Total parenteral nutrition  Somatostatin / octreotide treatment

30 Ursodeoxycholic Acid Protects against Gallstone Formation during Diet-Induced Rapid Weight Loss Shiffman et al., Ann Intern Med 1995;122:902 Men Women Placebo % of Patients UDCA Dose (mg/day)

31 Ursodeoxycholic Acid Protects against Gallstone Formation after Bariatric Surgery - Meta-analysis - Uy et al., Obes Surgery 2008;18:1532 Gallstone formation after bariatric surgery (n=521) UDCA 8.8 % Placebo27.7 % Relative risk (RR UDCA ) 0.43 ( )

32 Gewichtsreductie en cholecystolithiasis - NVVH Richtlijn  Elke vorm van gewichtsreductie van meer dan 1.5 kg / w bij patienten zwaarder dan 100 kg en / of < 7-10 g vet/d leidt tot een sterk verhoogde kans op galsteenvorming  600 mg / d UDCA is een adequate bescherming Mijnhout et al. NTvG 2004;148:174 Miller et al. Ann Surg 2003;238:697 Weinzier et al. Am J Med 1995;98:115 Niveau 2a

33 Prophylactic Use of Ursodeoxycholic Acid to Prevent Gallstone Formation  Rapid weight loss  Gene defects causing gallstone formation  MDR 3 / ABCB4 deficiency  Cholesterol 7  -hydroxylase deficiency Pullinger et al., J Clin Invest 2002;110:109 Rosmorduc et al., Gastroenterology 2001;120:1459 EASL Clinical Practice Guidelines, J Hepatol 2009;51:237

34 Ursodeoxycholzuur bij Galsteenlijden - Samenvatting - Ursodeoxycholzuur (>10 mg/kg/d ‘s avonds)  kan worden overwogen bij sterk geselecteerde symptomatische patienten en personen met verhoogd risico tot galsteenvorming  is beperkt door lange duur van behandeling en galsteen recurrence  is niet invasief en geassocieerd met zeer lage morbiditeit en geen mortaliteit


Download ppt "Ursodeoxycholzuur bij Galsteenlijden Delft, 26.1.2010 U. Beuers Afdeling Maag-, Darm- en Leverziekten Academisch Medisch Centrum Universiteit van Amsterdam."

Similar presentations


Ads by Google