Indications for Laparoscopic Cholecystectomy or Oral Dissolution Therapy with Ursodeoxycholic Acid in Symptomatic Gallstone Disease

Abstract

Andrea Cariati, Elisa Piromalli, Nicola Morelli, Giuliano Bottino, Enzo Andorno

Unconjugated bilirubin plays an important role in cholesterol gallstone formation. Patients with symptomatic gallstone disease who have high bilirubin plasma levels and/or are homozygous for the rs6742078 TT variant of the bilirubin glucuronidating gene UGT1A1 should not undergo oral dissolution therapy with ursodeoxycholic acid. A large Danish study has shown that high bilirubin plasma levels and the genetic variant rs6742078 TT of the enzyme bilirubin glucuronidase UGT1A1 are associated with an increased risk of developing symptomatic gallstone disease. Recent reports regarding the significant association between bilirubin levels and symptomatic gallstone disease open a new chapter about the indication and exclusion criteria for oral dissolution therapy of symptomatic gallstone disease. A highly select subgroup of patients with small, single, radiolucent cholesterol gallstones who received oral dissolution therapy with ursodeoxycholic acid (UDCA) had a reported recurrence of symptomatic gallstone disease of 50% over five years. This is probably related to the persistence of other causal risk factors for gallstones in addition to that of cholesterol suprasaturation. A subgroup of patients with high plasma bilirubin levels and the UGT1A1 genetic variant rs6742078 have a greater risk of recurrence. In conclusion, oral dissolution therapy with UDCA might still be appropriate for patients that refuse laparoscopic cholecystectomy provided they have small (< 0.5 cm), radiolucent cholesterol gallstones and a functioning gallbladder, and have mean plasma bilirubin levels below 1.33 mg/dL and are not homozygous for the UGT1A1 rs6742078 TT genotype.