Serum sterols in patients with primary biliary cirrhosis and acute liver failure before and after liver transplantation

Nikkilä, Katriina; Nissinen, Markku; Gylling, Helena; Isoniemi, Helena; Miettinen, Tatu A.

doi:10.1016/j.jhep.2008.07.026

Cited by 20 publications

(28 citation statements)

References 27 publications

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“…In addition, variables of cholesterol metabolism might add to the screening of liver function similarly as shown in PBC [11][12][13]. Although the liver essentially regulates the wholebody cholesterol homeostasis, this is, to our best knowledge, the first study investigating cholesterol metabolism in children with BA.…”

Section: Discussionmentioning

confidence: 90%

“…Of the other human noncholesterol sterols, plant sterols (eg, campesterol and sitosterol) are totally derived from dietary plants or plant oils and are weakly absorbed by the intestine; and the scarce amount absorbed is resecreted back into the bile [6][7][8]. Their serum levels reflect intestinal cholesterol absorption under normal conditions [5,9,10] and cholestasis [11][12][13]. Cholestanol is a noncholesterol sterol metabolite of cholesterol; and in addition to serving also as a surrogate marker of cholesterol absorption under normal conditions [5,10], it is a more sensitive serum marker of cholestasis than bilirubin in primary biliary cirrhosis (PBC) [11][12][13].…”

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confidence: 99%

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Surrogate markers of cholesterol metabolism in children with native liver after successful portoenterostomy for biliary atresia

Pakarinen

Lampela

Gylling

et al. 2010

Journal of Pediatric Surgery

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Section: Discussionmentioning

confidence: 90%

mentioning

confidence: 99%

Surrogate markers of cholesterol metabolism in children with native liver after successful portoenterostomy for biliary atresia

Pakarinen

Lampela

Gylling

et al. 2010

Journal of Pediatric Surgery

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“…On the other hand, diet-derived plant sterols (e.g., campesterol and sitosterol) and the liversynthesized cholesterol metabolite cholestanol are markers of cholesterol absorption efficiency [30] . These markers have been investigated in PBC before and after LT [15,28,[32][33][34] . Compared to that in healthy controls, intestinal cholesterol absorption is reportedly reduced by 2/3 in cases of prolonged severe intrahepatic cholestasis leading to cirrhosis and end-stage liver failure, as seen in PBC [35] .…”

Section: Difficulties Of Assessing Cholesterol Metabolism In Cholestasismentioning

confidence: 99%

“…However, striking increases of serum and hepatic plant sterol and cholestanol levels are also observed, indicating that the serum levels of plant sterols and cholestanol do not correctly mirror cholesterol absorption in cholestasis [15,28] . These changes can be used as biomarkers of the degree of cholestasis, with serum cholestanol/cholesterol being an even more sensitive marker of cholestasis among earlystage PBC patients than serum bilirubin [33] . Moreover, in end-stage cholestasis, serum cholestanol levels increase to levels that are otherwise only seen in the rare genetic disorder cerebrotendinous xanthomatosis [36] .…”

Section: Difficulties Of Assessing Cholesterol Metabolism In Cholestasismentioning

confidence: 99%

Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications

Nemes¹,

Åberg²,

Gylling³

et al. 2016

WJH

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The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers -such as cholesterol precursor sterols, plant sterols, and cholestanol -may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.

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“…This is especially the case for testing of agents or identifying conditions that interfere with cholesterol absorption. For example, Miettinen and colleagues ( 19 ) reported a reduction in plasma noncholesterol sterols in a variety of circumstances in which a reduction of cholesterol absorption was plausible or certain: during administration of plant stanols; after Roux-en-Y gastric bypass ( 20 ); in primary biliary cirrhosis ( 21 ); and in those with genetic forms of low cholesterol absorption ( 22 ). Reductions in absorption likewise have been reported by others during treatment with plant stanols ( 23 ), ezetimibe ( 24 -26 ), surfomer (AOMA) ( 10 ), sucrose polyester (olestra) ( 27 ), and Lactobacillus reuteri ( 28 ).…”

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Plasma noncholesterol sterols as indicators of cholesterol absorption

Grundy¹

2013

Journal of Lipid Research

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A publication by Jakulj et al. ( 1 ) in this issue of the Journal of Lipid Research calls into question the validity of plasma noncholesterol sterols for the evaluation of cholesterol absorption in humans. This method was fi rst proposed by Miettinen and coworkers ( 2 -5 ), who showed that either sitosterol/total cholesterol or campesterol/lathosterol ratios refl ect amounts of cholesterol absorbed by the intestine. Normally only small amounts of plant sterols (sitosterol and campesterol) are absorbed, but Miettinen and associates claimed that quantities absorbed are proportional to amounts of cholesterol absorbed. In turn, the greater the total of plant sterol absorbed, the higher will be the plasma level, normalized for plasma cholesterol levels. These investigators ( 4 , 6 , 7 ) further showed that plasma levels of a cholesterol synthesis precursor, lathosterol, refl ect the body's cholesterol synthesis rate. Because absorbed cholesterol returns to the liver and suppresses cholesterol synthesis, a low level of plasma lathosterol will denote reduced cholesterol synthesis because of more cholesterol absorption. Consequently, the campesterol/ lathosterol ratio should better indicate cholesterol absorption than the sitosterol/cholesterol ratio. Jakulj et al. ( 1 ) attempted to validate plant sterols in plasma as a marker of cholesterol absorption. To do so, they compared plasma campesterol/cholesterol ratios with cholesterol absorption in mildly hypercholesterolemic subjects. Fractional absorption of dietary cholesterol was determined by comparing isotope ratios of plasma cholesterol following oral and intravenous administration. They found no difference in fractional cholesterol absorption in those with the highest and lowest campesterol/ cholesterol ratios. Nor was there a correlation between these ratios and fractional absorption in the total population. The authors concluded that previous studies claiming a relationship between plasma sterol ratios and cholesterol absorption are of questionable validity.It might be noted that Jakulj et al.( 1 ) did not measure a marker of cholesterol synthesis, e.g., lathosterol. Because of the inverse relation between cholesterol absorption and synthesis, the addition of a synthesis precursor could have helped to validate the use of noncholesterol sterols as a marker for cholesterol absorption as well as synthesis.The overall design of the study of Jakulj et al.( 1 ) nonetheless is of interest. Testing whether subgroups with the highest and lowest plant sterol levels have a different fractional absorption of cholesterol is innovative and worthy of further evaluation. On the other hand, methodological issues raised by this study deserve consideration.The method for measuring fractional absorption of cholesterol employed a dual stable-isotope method ( 1 ). ]sitosterol in sunfl ower oil by gentle heating and stirring before adding it to stomach-soluble gelatin capsules. Cholesterol absorption was determined by differences in isotope ratios between oral administration and fecal...

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Serum sterols in patients with primary biliary cirrhosis and acute liver failure before and after liver transplantation

Cited by 20 publications

References 27 publications

Surrogate markers of cholesterol metabolism in children with native liver after successful portoenterostomy for biliary atresia

Surrogate markers of cholesterol metabolism in children with native liver after successful portoenterostomy for biliary atresia

Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications

Plasma noncholesterol sterols as indicators of cholesterol absorption

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