CHOLESTEROL CRYSTALLIZATION IN HUMAN GALLBLADDER BILE - RELATION TO GALLSTONE NUMBER, BILE COMPOSITION, AND APOLIPOPROTEIN E4 ISOFORM

Patients with multiple cholesterol gallstones are at increased risk of recurrence after nonsurgical therapy, possibly because of fast biliar y cholesterol crystallization. Serum apolipoprotein E4 (apo E4) is a r isk factor for primary cholesterol gallstone formation as well as recu rrence. We examined potential effects of stone number and apolipoprote in E genotype on crystallization and on various crystallization-influe ncing factors in gallbladder biles of 36 cholesterol stone patients (2 5 multiple stones: 10 carrying the epsilon 4 allele). Biliary choleste rol saturation, bile salt composition or concentrations of total prote in, immunoglobulin (Ig)A, IgC, alpha(1)-acid glycoprotein, haptoglobin , or mucin-all crystallization promoters-did not differ between multip le and solitary stone patients, apparently not explaining different sp eed of crystallization (crystal observation time 3.5 +/- 0.6 days vs. 12.7 +/- 2.4 days, respectively; P =.0003). In contrast, biliary amino peptidase-N activities (2,607 +/- 592 mU/mL vs. 947 +/- 185 mU/mL; P = .04) were higher and IgM levels (179 +/- 39 vs. 65 +/- 8 mg/L; P =.09) tended to be higher in the case of multiple stones. Although patients carrying the epsilon 4 allele had similar stone numbers and crystalli zation as patients without the epsilon 4 allele, their cholesterol sat uration index (CSI) was lower (1.08 +/- 0.09 vs. 1.54 +/- 0.13; P =.01 ), whereas total protein and bile salt concentrations tended to be hig her with preferential taurine-conjugation. In conclusion, fast cholest erol crystallization is associated with multiple stones but not with a polipoprotein epsilon 4. Whereas fast crystallization may contribute t o high recurrence rates after nonsurgical therapy in case of multiple gallstones, the mechanism for increased risk of gallstone formation in patients carrying the epsilon 4 allele remains unknown.