Apolipoprotein E4 genotype and gallbladder motility influence speed of gallstone clearance and risk of recurrence after extracorporeal shock-wave lithotripsy

✍ Scribed by P Portincasa; K J van Erpecum; P C van de Meeberg; G M Dallinga-Thie; T W A de Bruin; G P van Berge-Henegouwen

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 257 KB
• Volume: 24
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510240320

✦ Synopsis

as well as a high risk of recurrence after ESWL. This Extracorporeal shock-wave lithotripsy (ESWL) is an finding points to a possible role for genetic factors in effective treatment in selected gallstone patients, but the pathogenesis of cholesterol gallstones. Effective gallstone recurrence is a major drawback. Factors potenbladder emptying is important for speed of clearance tially influencing gallstone clearance and recurrence and prevention of recurrence. Patients with initial soliwere studied in 84 patients in whom stone dissolution tary stones have a decreased early-but not long-term was diagnosed after ESWL plus bile salt therapy for inigallstone recurrence rate. (HEPATOLOGY 1996;24:580tial solitary (n ! 55) or multiple (n ! 29) radiolucent 587.) stones. Apolipoprotein E (apoE) genotyping and gallbladder motility (sonography) were studied in a representative subgroup of patients (n ! 50). The median follow-up after ESWL was 36 months (range, 4.5-67 months).

Extracorporeal shock-wave lithotripsy (ESWL) with adju-Gallstone clearance was achieved after 8.7 months vant bile salt therapy to dissolve fragments is effective in (range, 0.2-30 months). Independent factors significantly selected patients with gallbladder stones. In the case of solienhancing gallstone clearance were the presence of E4 tary radiolucent gallstones with a diameter °20 mm, comallele; small initial gallstone size and number; effectiveplete clearance can be expected in 70% to 80% of patients ness of fragmentation; and good gallbladder emptying after a year of treatment. 1,2 Results, however, are consider-(P ! .002). Gallstone recurrence was seen in 30 patients ably less favorable for patients with larger or multiple gallafter 18.6 months (range, 1.0-50 months). Cumulative stones. A major drawback of nonsurgical therapy is the risk gallstone recurrence rate (life-table analysis) was 15% of gallstone recurrence after initially successful treatment. within 1 year, increasing to 60% within 5.5 years. Al-Previous studies on patients treated with oral bile salts sugthough the probability of gallstone recurrence tended gested a 50% recurrence rate at a 5-year follow-up with low or to be smaller in patients with initial solitary stones than no recurrence thereafter. 3,4 The fact that gallstone recurrence in those with multiple stones during early follow-up, difoccurs in only one half of the patients suggests the existence ferences disappeared after long-term follow-up. Effecof two subgroups of patients, one with a permanent and the tive gallbladder emptying (residual volume Ù6 mL) and other with a transient defect (e.g., pregnancy, oral contracepapolipoprotein E4 (apoE4) independently influenced tives, postmenopausal estrogens, weight loss in obese pagallstone recurrence. Recurrence rate was higher (log tients, and major abdominal surgery: all considered risk facrank test, P ! .037) in those patients who were homozytors for gallstone development). In particular, patients with gous and heterozygous for the E4 allele compared with initially multiple gallstones have been reported to have a the individuals who were not expressing the apoE4 alhigh risk of recurrence. 3 This may relate to increased activity lele. Accordingly, there was an overrepresentation of the of biliary nucleation promoting proteins in the case of multiallele frequency for E4 in the group with gallstone recurple gallstones. 5,6 The role of genetic factors might also be rence (P ! .03). Patients with small postprandial residual important in cholesterol cholelithiasis. 7 Apolipoprotein E gallbladder volumes (Ù6 mL) had a lower probability of (apoE) plays an essential role in cholesterol metabolism. 8 The stone recurrence than those with large residual gallheterozygous and homozygous phenotypes of apoE are genetibladder volumes (log rank test, P ! .0215). Biliary pain cally determined by three alleles (E2, E3, and E4) at a single was more frequent with recurrence (55% vs. 13%, P ! gene locus on chromosome 19 and are related to plasma lipo-.001). The present study indicates that apoE4 genotype protein cholesterol levels. 9 The genetic polymorphism of apoE is associated with increased speed of gallstone clearance can affect the efficiency of the intestinal absorption of cholesterol, the hepatic synthesis, and the biliary secretion of cholesterol and bile salts, 9 which, in turn, might influence the Abbreviations: ESWL, extracorporeal shock-wave lithotripsy; apoE, apolipoprotein E; cholesterol solubility in bile. Indeed, it has recently been NSAIDs, nonsteroidal anti-inflammatory drugs; UDCA, ursodeoxycholic acid; AUC, area shown that expression of apoE4 is associated with increased under curve.