Factors Influencing Gallstone Formation: A Review of the Literature

Abstract

Gallstone disease is a common pathology of the digestive system with nearly a 10-20% incidence rate among adults. The mainstay of treatment is cholecystectomy, which is commonly associated with physical pain and may also seriously affect a patient's quality of life. Clinical research suggests that cholelithiasis is closely related to the age, gender, body mass index, and other basic physical characteristics of patients. Clinical research further suggests that the occurrence of cholelithiasis is related to obesity, diabetes, non-alcoholic fatty liver, and other diseases. For this reason, we reviewed the following: genetic factors; excessive liver cholesterol secretion (causing cholesterol supersaturation in gallbladder bile); accelerated growth of cholesterol crystals and solid cholesterol crystals; gallbladder motility impairment; and cardiovascular factors. Herein, we summarize and analyze the causes and mechanisms of cholelithiasis, discuss its correlation with the pathogenesis of related diseases, and discuss possible mechanisms.

Keywords: bile acids; cardiovascular disease; diabetes; gallstone disease; non-alcoholic fatty liver; obesity.

Figure 1

Cholesterol synthesis metabolism and bile acid hepatoenteric circulation. Cholesterol can be de novo synthesized. Part of the cholesterol in hepatocytes is converted into bile salts, and the other part of free cholesterol is pumped out by hepatocytes through ABCG5/8 into the biliary tract. Cholesterol is absorbed by NPC1L1 on the membranes of intestinal epithelium, which then enters the bloodstream through the lymphatic system. The newly synthesized binding bile acids are secreted into the capillary bile duct of hepatocytes by ABCB11, eventually making their way into the intestine. Binding bile acids can be effectively reabsorbed into intestinal epithelial cells at the terminal ileum by ASBT, which binds to ileal bile acid binding protein for transport to the basement membrane. In the presence of heterodimer OSTα/β at the terminal cavity of the basement membrane, bile acids are reabsorbed and transported to the liver via the portal vein. Orange represents cholesterol. Dark green represents the bile acid cycle. NPC1L1:Niemann–Pick C1-Like Protein1; ABCG5/8: ATP Binding Cassette Subfamily G Member 5/8; CYP7A1: cholesterol 7α–hydroxylase; CYP27A1: sterol 27-hydroxylase; ABCB11: ATP-Binding Cassette Sub-Family B Member 11; ASBT: the apical sodium-dependent bile acid transporter; OSTα/β: organic solute transporter α/β.

Figure 2

Influence factors of gallstones. CVD: cardiovascular disease.