Apolipoprotein E4 Genotype and Gallbladder Motility Influence Speed of Gallstone Clearance and Risk of Recurrence After Extracorporeal Shock–Wave Lithotripsy

Abstract

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;24:580-tial 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 adjuGallstone 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; effective-plete 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, dif-occurs in only one half of the patients suggests the existence ferences disappeared after long-term follow-up. Effec-of 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 homozy-tors for gallstone development). In particular, patients with gous and heterozygous for the E4 allele compared with initially multip...

Apolipoprotein E genotype and the risk of gallbladder disease in pregnancy

“…Bertomeu et al 11 studied patients known to have symptomatic gallstones cross-sectionally, such that data about serum lipid levels, behavioral habits, and dietary composition could not be collected during the actual period of gallstone formation. Portincasa et al 10 studied a group with a high risk of developing gallstones, including patients with previously documented gallstones that had been treated by extracorporeal shock wave lithotripsy. These studies were thus limited to studying risk factors for prevalent or recurrent stones instead of examining risk factors before and during the period of initial stone formation.…”

“…Genetic variation in cholesterol metabolism may thus play a role. One protein proposed to be associated with gallstones is apolipoprotein E (apoE), 10,11 which is a component of very low-density lipoproteins and high-density lipoproteins (HDL). ApoE mediates binding of lipoprotein particles to low-density lipoproteins (LDL) and chylomicron remnant receptors and regulates the plasma cholesterol response to dietary cholesterol intake.…”

“…[15][16][17][18][19] Previous studies have shown that the E4 allele is associated with an end stage of gallstone formation, namely symptomatic gallstones. 10,11,20,21 After lithotripsy for treatment of gallstones, presence of the apoE4 allele was associated with a significantly higher rate of gallstone recurrence over 5 years (P ϭ .004). 10 A separate study showed that the frequency of the apoE4 allele was significantly greater in patients with gallstones (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.23-5.93) and patients undergoing cholecystectomy (OR, 3.62; 95% CI, 1.49-8.91) than in controls.…”

“…10,11,20,21 After lithotripsy for treatment of gallstones, presence of the apoE4 allele was associated with a significantly higher rate of gallstone recurrence over 5 years (P ϭ .004). 10 A separate study showed that the frequency of the apoE4 allele was significantly greater in patients with gallstones (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.23-5.93) and patients undergoing cholecystectomy (OR, 3.62; 95% CI, 1.49-8.91) than in controls. 11 However, this association has not been confirmed in other studies.…”

Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis†‡

“…Patients were characterized as strong (minimum postprandial volume Յ6 mL) or weak (minimum postprandial volume Ͼ6 mL) contractors. 31,32 Plasma CCK Measurement. Blood samples for the measurement of CCK concentrations were collected in the fasting state and at 15-minute intervals during a 2-hour period postprandially.…”