The effects of chenodiol on biliary lipids and their association with gallstone dissolution in the National Cooperative Gallstone Study (NCGS).

Grundy, Scott M.; Lan, Shu-Ping; Lachin, John M.

doi:10.1172/jci111301

Cited by 25 publications

(7 citation statements)

References 23 publications

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“…Biliary lipids were measured after extraction (25) and bile acids, phospholipids, and cholesterol were measured as described previously (12). Serum cholesterol, cholestanol, campesterol, and sitosterol were analyzed by gas-liquid chromatography (GLC) (4).…”

Section: Methodsmentioning

confidence: 99%

Serum plant sterols and biliary cholesterol secretion in humans

Lindenthal

Sudhop

Sartipy

et al. 2002

Journal of Lipid Research

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Ratios of cholestanol, campesterol, and sitosterol to cholesterol in serum are known to reflect cholesterol absorption efficiency. Here, a possible link between these ratios and biliary secretion rates of cholesterol was investigated. Biliary lipid secretion rates and serum sterols were determined in 13 patients with gallstones. Seven were treated with ursodeoxycholic acid (UDCA) (1,000 mg/d). Serum cholesterol and non-cholesterol sterols were also measured in a cross over study in 20 healthy volunteers, who received either placebo or UDCA (750 mg/d). Biliary cholesterol secretion was significantly lower, whereas the non-cholesterol sterols and their ratio to cholesterol were higher in patients with gallstones treated with UDCA. A highly significant negative linear correlation between the ratios of non-cholesterol sterols to cholesterol and biliary cholesterol secretion was observed. In volunteers, administration of UDCA for 4 weeks was followed by a significant increase in non-cholesterol sterols and their ratios. Even 4 weeks after discontinuing UDCA administration, campesterol and sitosterol were still significantly higher than pretreatment levels, which was also true for the campesterolcholesterol ratio after 8 weeks. The results suggest that the ratios of cholestanol, campesterol, and sitosterol to cholesterol can be used as indicators of changes in biliary cholesterol secretion rates. Cholestanol and the two plant sterols campesterol and sitosterol are present in low concentrations in human blood (1, 2), but their concentrations are 400-to 1,000-fold lower than cholesterol (1). The concentrations in serum are the results of synthesis (for cholestanol only), absorption efficiency (campesterol and sitosterol), lipoprotein metabolism, and rate of hepatic excretion into bile (3). They are absorbed from the intestine to a much lesser extent than cholesterol (4, 5). Cholestanol is synthesized in the liver from cholesterol (6), and is almost absent from the diet. Whereas sitosterol is not metabolized to a significant extent in humans (7), a conversion of cholestanol to bile acids has been reported (6). The ratios of cholestanol, campesterol, and sitosterol to cholesterol in serum have been shown to correlate positively with the cholesterol absorption efficiency (2, 8), and have therefore been regarded as markers for changes in the absorption of cholesterol (8-10).Recently it has been reported that treatment with ursodeoxycholic acid (UDCA), a bile acid known to reduce the hepatic secretion of cholesterol (11-14), increases serum concentrations of plant sterols and cholestanol in patients with primary biliary cirrhosis (15) and patients with radiolucent gallstones (16,17). Considering that cholesterol absorption is not affected or even reduced by UDCA (13,14,(18)(19)(20)(21), we thought that these results were not consistent with the observation that the ratio of plant sterols to cholesterol are only markers of cholesterol absorption efficiency. The purpose of the present study was to examine whether the ...

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Section: Methodsmentioning

confidence: 99%

Serum plant sterols and biliary cholesterol secretion in humans

Lindenthal

Sudhop

Sartipy

et al. 2002

Journal of Lipid Research

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“…A rate of 24-38% has been reported for treatment with UDCA alone [54,55]. Although UDCA and CDCA share a common mechanism of action (i.e., increasing the solubility of cholesterol in bile) [56], the safety and efficacy of UDCA are reported to be superior [57,58]. Since CDCA was shown to cause diarrhea at a relatively high frequency and possibly have transient effects on liver dysfunction and serum lipid levels, its use in general clinical practice has decreased [59].…”

Section: Commentarymentioning

confidence: 99%

Evidence-based clinical practice guidelines for cholelithiasis 2016

Tazuma

Unno²,

Igarashi³

et al. 2016

J Gastroenterol

214

178

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Cholelithiasis is one of the commonest diseases in gastroenterology. Remarkable improvements in therapeutic modalities for cholelithiasis and its complications are evident. The Japanese Society of Gastroenterology has revised the evidence-based clinical practice guidelines for cholelithiasis. Forty-three clinical questions, for four categories-epidemiology and pathogenesis, diagnosis, treatments, and prognosis and complications-were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This article preferentially describes the clinical management of cholelithiasis and its complications. Following description of the diagnosis performed stepwise through imaging modalities, treatments of cholecystolithiasis, choledocholithiasis, and hepatolithiasis are introduced along with a flowchart. Since there have been remarkable improvements in endoscopic treatments and surgical techniques, the guidelines ensure flexibility in choices according to the actual clinical environment. The revised clinical practice guidelines are appropriate for use by clinicians in their daily practice.

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“…This hypothesis could explain why oral bile acids are much more effective at desaturating bile than they are at dissolving cholesterol gallstones [7]. The current recommendation of most authorities is that asymptomatic stones should not be treated [18].…”

Section: Implications For Nonsurgical Therapymentioning

confidence: 99%

Solitary versus multiple cholesterol gallbladder stones

Wolpers¹,

Hofmann

1993

Clin Investig

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The development and growth pattern of solitary and multiple cholesterol gallbladder stones was defined using cholecystography in a prospective study of 48 patients whose initial cholecystograms indicated a stone-free gallbladder and who developed gallstones within the subsequent 5 years. Radiological observations performed over 365 patient-years were complemented by macroscopic examination, radiograms, scanning electron microscopy, and chemical analysis of gallstones from these and other patients obtained at cholecystectomy. Solitary gallstones were found to develop after a precursor phase of over 2 years during which free-floating crystal laminae of cholesterol formed. These laminae subsequently aggregated loosely and underwent external compaction and internal remodeling by movement of cholesterol molecules to form compact spheroids. A single lamina was observed to function as a nucleus for the development of a solitary stone shaped as an ellipsoid. About 10% of solitary stones were found to have a solitary pigment stone in their center. In contrast, multiple cholesterol gallstones formed without a precursor phase. Innumerable, very thin cholesterol crystals appeared which very abruptly aggregated to form spheres of up to 1 mm in diameter. Within 3 months a second aggregation took place in which these spheres colaesced to form mulberry stones. Mulberry stones in turn were transformed either to faceted stones (if many were present in the gallbladder) or to barrel stones (if few were present) over a period of 3 years. It is proposed that temporary occlusion of the cystic duct leads to supersaturation of bile with calcium bilirubinate and/or calcium carbonate which in turn promotes deposition of either or both of these calcium salts on the surface of single or multiple gallstones. For multiple gallstones, this process or the deposition of additional cholesterol crystals seals the gallstone surface and is followed by metamorphosis of the stone center.

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The effects of chenodiol on biliary lipids and their association with gallstone dissolution in the National Cooperative Gallstone Study (NCGS).

Cited by 25 publications

References 23 publications

Serum plant sterols and biliary cholesterol secretion in humans

Serum plant sterols and biliary cholesterol secretion in humans

Evidence-based clinical practice guidelines for cholelithiasis 2016

Solitary versus multiple cholesterol gallbladder stones

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