Table 1: Non genetic risk factors for gallbladder stones
including modifiable, potentially modifiable and non-modifiable factors.
Factor |
|
Pathogenic
mechanism (s) |
Stone
Type |
Intervention |
Dietary |
|
|
|
|
|
Westernized
diet -
high-calorie -
low-fiber -
high-refined carbohydrate -
high-lipid |
Hepatic hypersecretion,
associated metabolic factors, gallbladder stasis |
Cholesterol |
Modifiable |
Lifestyles |
|
|
|
|
|
Rapid
weight loss (bariatric surgery of morbid obesity), very low calorie diet) |
Hypersecretion
of biliary mucin, hepatic hypersecretion,
gallbladder stasis |
Cholesterol |
Modifiable |
|
Physical
inactivity (especially in men) |
hepatic hypersecretion, intestinal
and gallbladder hypomotility, decreased excretion
of bile acids, increased serum triglycerides and insulin release |
Cholesterol |
Modifiable |
|
Smoking |
Metabolic
factors? Others? |
Cholesterol/Pigment
|
Modifiable |
|
High
Alcohol intake |
Liver
damage, reduced bile
acid synthesis |
Black
pigment |
Modifiable |
Associated |
|
|
|
|
|
Obesity |
hepatic hypersecretion,
gallbladder stasis |
Cholesterol |
Modifiable |
|
Metabolic syndrome, Insulin resistance |
Obesity,
hepatic hypersecretion,
dyslipidemia |
Cholesterol |
Modifiable |
|
Hypertriglyceridemia |
Association
with other metabolic abnormalities, hepatic hypersecretion of cholesterol |
Cholesterol |
Modifiable |
|
Micronutrients
abnormalities: low serum magnesium |
Insulin resistance and deranged serum
LDL- and HDL-cholesterol |
Cholesterol |
Modifiable |
|
Vitamin
B-12/folic acid deficient diet |
Hemolytic
anemia |
Black
pigment |
Modifiable |
|
Pregnancy |
Steroid hormones, gallbladder stasis,
hepatic hypersecretion |
Cholesterol |
Potentially
modifiable |
|
Gallbladder
stasis (total parenteral nutrition, total gastrectomy
with lymph node dissection, vagotomy, spinal cord
injury, somatostatinoma, octreotide) |
Increased bile concentration and
precipitation/crystallization of cholesterol |
Cholesterol |
Potentially
modifiable |
|
Estrogens
and oral contraceptives. |
Hepatic hypersecretion,
gallbladder stasis |
Cholesterol |
Potentially
modifiable |
|
Drugs:
fibrates, octreotide, ceftriaxone, calcineurin inhibitors (tacrolimus,
ciclosporin) |
Precipitation
in bile (ceftriaxone), hepatic
hypersecretion, inhibition of hepatic bile salt export pump, bile
concentration |
Cholesterol |
Potentially
modifiable |
|
Diabetes
mellitus* |
Metabolic
abnormalities, gallbladder stasis, autonomic neuropathy |
Cholesterol |
Potentially
modifiable |
Others |
|
|
|
|
|
Female
gender |
Pregnancies, steroid hormones,
hepatic hypersecretion |
Cholesterol |
Non-modifiable |
|
Increasing age |
Metabolic
risks, hemolytic anemia |
Cholesterol, Pigment |
Non-modifiable |
|
Hemolytic
anemia, sickle cell disease |
Increased calcium bilirubinate
concrements, gallbladder stasis |
Black
pigment |
Non-modifiable/
Potentially modifiable |
|
Liver
cirrhosis |
Gallbladder
stasis, hyperestrogenism, bile salt malabsorption, increased enterohepatic
circulation of bilirubin |
Black
pigment/Cholesterol |
Non-modifiable/Potentially
modifiable |
|
Cystic fibrosis |
Increased biliary concentration of
conjugated and unconjugated bilirubin and calcium, increased enterohepatic circulation of bilirubin |
Black
pigment |
Non-modifiable/Potentially
modifiable |
|
Crohn’s disease,
extended ileal resection |
Increased biliary concentration of
conjugated and unconjugated bilirubin and calcium, increased enterohepatic circulation of bilirubin |
Cholesterol/Black
pigment |
Non-modifiable/Potentially
modifiable |
|
Infections
(e.g., biliary strictures, duodenal diverticula, cholangitis, pancreatic
insufficiency) Bile
duct (Clonorchis sinensis, Ascaris lumbricoides, Opistorchis viverrini) HCV
infection |
Bacterial
b-glucuronization with biotransformation of conjugated to
unconjugated bilirubin, precipitation together with calcium and long-chain
fatty acids |
Black
pigment/brown pigment |
Non-modifiable/Potentially
modifiable |
*conditions especially associated with gallbladder
stasis. Adapted from Portincasa et al. [2,49] with permission.