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Epidemiology, Pa Tho Genesis, And Classification of Biliary Stones

Epidemiology, Pa Tho Genesis, And Classification of Biliary Stones

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7Epidemiology, pathogenesis, and classificationof biliary stones (common bile ductand intrahepatic)
Susumu Tazuma*
Professor and Chairman
Department of General Medicine and Clinical Pharmacotherapeutics, Hiroshima University Hospital and Graduate School of Biomedical Sciences, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan
Gallstones are common in Western countries and Japan. Most gallstones are found in the gall-bladder, but they sometimes pass through the cystic duct into extrahepatic and/or intrahepaticbile ducts to become bile-duct stones, causing conditions known as choledocholithiasis and hep-atolithiasis. Some 10
15% of gallstone patients concomitantly suffer from bile-duct stones. Bile-duct stones can also be formed in the absence of gallbladder stones, and such primary bile-ductstones are more common in East Asian countries than in the Western world. Thus pathogenesisof primary and secondary bile-duct stones is unlikely to be similar. Furthermore, the gallbladderstones are primarily cholesterol or black-pigment stones, whereas most bile-duct stones arebrown-pigment stones (calcium bilirubin stones). Thus, epidemiology, pathogenesis and classifi-cation of biliary stones are very likely to differ according to stone location (intrahepatic and/orextrahepatic bile duct).
Key words:
choledocholithiasis; hepatolithiasis; cholesterol gallstone; pigment gallstone; bileinfection; bile stasis.
COMMON-BILE-DUCT STONESIncidence and distribution
Gallstones are extremely common in Western societies and also in Japan. Approxi-mately l5% of the American population is foundto have gallstones, and over 0.7 millioncholecystectomies are performed every year.
Of these, 10
15% cases are found tohave concomitant common-bile-duct (CBD) stones, but in the Western world few
* Tel./Fax:
81 82 257 5461.
E-mail address
:stazuma@hiroshima-u.ac.jp1521-6918/$ - see front matter
2006 Elsevier Ltd. All rights reserved.Best Practice & Research Clinical GastroenterologyVol. 20, No. 6, pp. 1075
1083, 2006
doi:10.1016/j.bpg.2006.05.009available online athttp://www.sciencedirect.com
cases are reported with CBD stones in the absence of gallbladder stones. In contrast,in Japan the overall incidence of gallstones is approximately 10% of the population.
Among these, the incidence of bile-duct stones increases with age to become approx-imately 20% of all gallstones. The gallbladder stones are concomitantly found in 67% of CBD-stone cases, whereas the prevalence of CBD stones in gallbladder-stone cases is15% (Table 1). Thus, the gallstone incidence in Japan is epidemiologically similar to thatin the Western world. In addition, the prevalence of asymptomaticCBD stones,coincidently detected at cholecystectomy, is 6% in Western countries.
Coexistinggallbladder and CBD stones are correlated with increasing age, chronic bile-ductinflammation, Asian descent, and possibly hypothyroidism.Primary bile-duct stones which are not associated with gallbladder stones occurfrequently in Asia. This is associated with the high incidence of intrahepatic bile-duct stones seen primarily in Southeast Asian countries, Taiwan, Hong Kong, andSingapore.
The relative prevalence of intrahepatic bile-duct stones in all gallstonecases in Taiwan is extremely high (
50%), and coexisting intra- and extrahepaticbile-duct stones are found in approximately 70% of these. Primary bile-duct stonesare composed predominantly of bilirubin, regardless of the concomitant presence of intrahepatic bile-duct stones, whereas those secondary to gallbladder stones are com-posed mainly of cholesterol. Thus, the pathogenesis of the two types of bile-ductstones probably differs.The ratio of women to men with CBD stones is 0.89:1,
although the prevalence of gallbladder stones is higher in women than in men (1.22:1). The incidence of gallstonesincreases with increasing parity, and biliary sludge is ormed in approximately 30% of pregnant women; 1
3% of these form gallstones.
The mean age of CBD-stonepatients is 67 years, which is older than that of gallbladder-stone patients (56 years).Similarly, gallbladder diseasesare found in 5
8% of young women but in 25
30% of women over 50 years of age.
Thus, risk factors for gallstones include biological fac-tors such as increasing age, female gender, and pregnancy.
secondary to gallbladder or primitive from the bile duct?
CBD stones are classified according to origin: (1) primary bile-duct stones, forminginitially in the bile ducts; (2) secondary to gallbladder stones, originating in the gallblad-der and passing into the bile ducts; and (3) secondary to or coexisting with intrahe-patic bile-duct stones.Primary bile-duct stones which do not involve the gallbladder are also composedpredominantly of bilirubin, and this is presumably associated with biliary stasis andinfection.
The incidence of primary CBD stones is low in Western societies, wherestones are most commonly found in the gallbladder. Gallstones can pass through the
Table 1.
Incidence of common bile-duct stones in Japan.1989
1995 1996
1997All gallstone cases 140,884 6814Gallbladder stone 117,920 (83.7%) 5335 (78.3%)Common bile-duct stone 20,006 (14.2%) 1384 (20.3%)With gallbladder stone
934/1384 (67.5%)Without gallbladder stone
450/1384 (32.5%)Intrahepatic duct stone 2959 (2.1%) 95 (1.4%)1076 S. Tazuma
cystic duct into extrahepatic and/or intrahepatic bile duct to become bile-duct stonessecondary to gallbladder stones. In this regard, bile-duct stones coexisting with gall-bladder stones are presumably formed secondarily to gallbladder stones. In such cases,the bile-duct stone composition is biochemically identical or extremely similar to thatof gallbladder stones, which are composed predominantly of cholesterol.In addition, CBD stones are concomitantly found in approximately 70% of intrahe-patic bile-duct stones.
These stones are identical or extremely similar to intrahepaticbile-duct stones in biochemical composition. Most of intrahepatic bile-duct stones arebrown-pigment stones, relatively rich in cholesterol. Thus, the pathogenesis of primarybile-duct stones probably differs from that of secondary bile-duct stones.
Congenital and acquired risk factors
Risk factors for gallstones include congenital, biological, and behavioural factors. Bilestasis and infection are important factors for primary CBD-stone formation. Onthis basis, an anatomical abnormality causing bile stasis is one of the major risk factors,in association with bile infection.
In contrast, the dilatation of the common bile duct isfrequently associated with bile-duct stones after cholecystectomy, and a cystic ductdilatation in the aged gallbladder-stone population is directly associated with passageof gallbladder stones into bile ducts to form secondary bile-duct stones. Thus, suchan acquired risk in anatomy is also important in both primary and secondary bile-duct stone formation.Genetic factors are believed to account for the ethnic difference in the risk of gall-stone formation. The prevalence of cholesterol gallstones is higher in Native Americans,Chileans, and Hispanics than in age-matched white control subjects, whereas AfricanAmericans have a lower prevalence of gallstones than whites,
and concomitant CBDstones are found in 10
15% of these populations. Primary bile-duct stones, composedmainly of bilirubin, are much more common in Asians than in Europeans. Anothergenetic factor, gallstone formation-associated genes Lith1 and Lith2, have beenrecognized in mice,
but no human genes definitely linked to gallstones have beenidentified to date. Furthermore, polymorphisms in the apolipoprotein E gene, whichare associated with gallstone formation, have been identified.
However, these geneticfactors are not specific for primary bile-duct gallstone formation.Acquired risk factors for gallstone formation include not only biological factorssuch as age, gender, and lipid metabolism, but also behavioural factors such as nutri-tion, obesity, rapid weight gain and loss, and exercise. In addition to these factors, cho-lecystectomy atyoung ages leading to CBD dilatation is another acquired risk factorfor CBD stones.
Furthermore, chronic inflammatory conditions
such as hypofunc-tion of Oddi, primary sclerosing cholangitis, acquired immunodeficiency syndrome,and parasites
can lead to bile-duct stone formation. Certain drugs are secretedinto bile and may precipitate with calcium to form stones.
Classification based on biochemical structure
CBD stones are composed predominantly of bilirubin, whereas cholesterol is a majorcomponent in gallbladder stones (Table 2). Thus, primary bile-duct stones tend to behigher in bilirubin content and lower in cholesterol content than secondary stones.The pathogenesis of primary bile-duct stones probably differs from that of secondarybile-duct stones.
Epidemiology, pathogenesis, and classification of biliary stones 1077

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