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

Pakarinen, Mikko P.; Lampela, Hanna; Gylling, Helena; Miettinen, Tatu A.; Koivusalo, Antti; Nissinen, Markku

doi:10.1016/j.jpedsurg.2009.10.061

“…Twenty-two studies were identified, of which five studies were performed in patients with steatosis [95,96,97,98,99], eleven studies in patients with cholestasis [100,101,102,103,104,105,106,107,108,109,110], and six studies included patients with liver diseases related to cirrhosis or necrosis [111,112,113,114,115,116] (Table 8).…”

Section: Resultsmentioning

confidence: 99%

Non-Cholesterol Sterol Concentrations as Biomarkers for Cholesterol Absorption and Synthesis in Different Metabolic Disorders: A Systematic Review

Mashnafi

¹

,

Mensink

²

,

Baumgartner

³

2019

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Non-cholesterol sterols are validated biomarkers for intestinal cholesterol absorption and endogenous cholesterol synthesis. However, their use in metabolic disturbances has not been systematically explored. Therefore, we conducted a systematic review to provide an overview of non-cholesterol sterols as markers for cholesterol metabolism in different metabolic disorders. Potentially relevant studies were retrieved by a systematic search of three databases in July 2018 and ninety-four human studies were included. Cholesterol-standardized levels of campesterol, sitosterol and cholestanol were collected to reflect cholesterol absorption and those of lathosterol and desmosterol to reflect cholesterol synthesis. Their use as biomarkers was examined in the following metabolic disorders: overweight/obesity (n = 16), diabetes mellitus (n = 15), metabolic syndrome (n = 5), hyperlipidemia (n = 11), cardiovascular disease (n = 17), and diseases related to intestine (n = 16), liver (n = 22) or kidney (n = 2). In general, markers for cholesterol absorption and synthesis displayed reciprocal patterns, showing that cholesterol metabolism is tightly regulated by the interplay of intestinal absorption and endogenous synthesis. Distinctive patterns for cholesterol absorption or cholesterol synthesis could be identified, suggesting that metabolic disorders can be classified as ‘cholesterol absorbers or cholesterol synthesizers’. Future studies should be performed to confirm or refute these findings and to examine whether this information can be used for targeted (dietary) interventions.

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“…The present study indicated that the children with BPS were characterized by high serum and stone proportions of cholestanol. Cholestanol is a noncholesterol sterol metabolite of cholesterol that serves as a surrogate marker of cholesterol absorption under normal physiological conditions and reflects sensitively cholestasis in primary biliary cirrhosis and biliary atresia [ 34 , 35 ]. Paralleling these findings, in BPS patients of the present study, serum bile acid concentration and stone composition of cholestanol (but not plant sterols) were positively interrelated suggesting that high cholestanol proportions in the stones of the BPS group could partly be explained by cholestasis.…”

Section: Discussionmentioning

confidence: 99%

Relation of cholesterol metabolism to pediatric gallstone disease: a retrospective controlled study

Koivusalo

¹

,

Pakarinen

²

,

Gylling

³

et al. 2015

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BackgroundCholesterol metabolism may be involved in pediatric gallstone disease. We aimed to reveal cholesterol metabolites and phytosterols and their relation to stone composition of sterols in children having black pigment and cholesterol stones.MethodsWe performed retrospective controlled clinical study, in which we examined parameters of cholesterol metabolism and liver function values in serum (n = 28) and gallstones (n = 46) of consecutively cholecystectomized children. Serum values of age-, body mass index- and sex-matched children (n = 82) and adult gallstones (n = 187) served as controls.ResultsSurrogate markers of cholesterol synthesis in serum (squalene/cholesterol, cholestenol/cholesterol and lathosterol/cholesterol) were 26–52 % higher in both stone subclasses compared to controls (p < 0.05 for all). Respectively, cholestanol/cholesterol and plant sterols campesterol/cholesterol and sitosterol/cholesterol (cholesterol absorption markers) had decreasing order in serum: black pigment stone group > controls > cholesterol stone group (p < 0.05 for all). In black pigment stone group, stone cholestanol/cholesterol was associated with serum bile acids (r = 0.620, p = 0.018). In cholesterol stone group, surrogate markers of cholesterol synthesis in serum (e.g., lathosterol/cholesterol) inversely reflected those of absorption (r-range -0.633–-0.706, p-range 0.036–0.015). In cholesterol stone group, serum and stone lathosterol/cholesterol and cholestanol/cholesterol were positively interrelated (r-range 0.727–0.847, p < 0.05 for both).ConclusionsGallstone subclasses shared enhanced cholesterol synthesis. Cholesterol stone children were low cholesterol absorbers with intact homeostasis of cholesterol metabolism. Black pigment stone group was characterized by deteriorated cholesterol metabolism, and accumulation of cholestanol, campesterol and sitosterol in serum and stones suggesting their participation in pathogenesis.

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“…Twenty-two studies were identified, of which five studies were performed in patients with steatosis [95][96][97][98][99], eleven studies in patients with cholestasis [100][101][102][103][104][105][106][107][108][109][110], and six studies included patients with liver diseases related to cirrhosis or necrosis [111][112][113][114][115][116] (Table 8). [102] Cases (n = 45) 3.00 ± 1.10 ↑ Controls (n = 80)…”

Section: Serum Non-cholesterol Sterol Markers In Subjects With Liver mentioning

confidence: 99%

Non-Cholesterol Sterol Concentrations As Biomarkers For Cholesterol Absorption And Synthesis In Different Metabolic Disorders: A Systematic Review

Mashnafi

¹

,

Mensink

²

,

Baumgartner

³

2019

View full text Add to dashboard Cite

Non-cholesterol sterols are validated biomarkers for intestinal cholesterol absorption and endogenous cholesterol synthesis. However, their use in metabolic disturbances has not been systematically explored. Therefore, we conducted a systematic review to provide an overview of non-cholesterol sterols as markers for cholesterol metabolism in different metabolic disorders. Potentially relevant studies were retrieved by a systematic search of three databases in July 2018 and ninety-four human studies were included. Cholesterol-standardized levels of campesterol, sitosterol and cholestanol were collected to reflect cholesterol absorption and those of lathosterol and desmosterol to reflect cholesterol synthesis. Their use as biomarkers was examined in the following metabolic disorders: overweight/obesity (n = 16), diabetes mellitus (n = 15), metabolic syndrome (n = 5), hyperlipidemia (n = 11), cardiovascular disease (n = 17), and diseases related to intestine (n = 16), liver (n = 22) or kidney (n = 2). In general, markers for cholesterol absorption and synthesis displayed reciprocal patterns, showing that cholesterol metabolism is tightly regulated by the interplay of intestinal absorption and endogenous synthesis. Distinctive patterns for cholesterol absorption or cholesterol synthesis could be identified, suggesting that metabolic disorders can be classified as 'cholesterol absorbers or cholesterol synthesizers'. Future studies should be performed to confirm or refute these findings and to examine whether this information can be used for targeted (dietary) interventions.Nutrients 2019, 11, 124 2 of 31 procedures [5]. The only direct method to measure intestinal cholesterol absorption in humans is the intestinal perfusion technique using radioisotopes [6], whereas cholesterol balance and isotope ratio methods can be used to indirectly calculate cholesterol absorption. Cholesterol absorption using stable isotopes can be estimated using the dual plasma isotope ratio method, continuous isotope feeding, or single stable isotopes [5]. For quantifying endogenous cholesterol synthesis, other techniques such as cholesterol balance, fractional conversion of squalene, mass isotopomer distribution analysis (MIDA), and deuterium incorporation (DI) are used. Overall, the cholesterol balance technique, dual plasma isotope ratio, and continuous isotope feeding are the gold standard methods to quantify respectively cholesterol synthesis and absorption. These methods were developed and validated many years ago [7][8][9][10]. However, although these techniques are very precise, they are also complex, laborious, expensive and require a steady-state condition. Thus, these techniques are only suitable for small-scale in-depth studies, but not for large-scale intervention studies [11]. Consequently, there is a clear need for alternative approaches to monitor intestinal cholesterol absorption and endogenous cholesterol synthesis. In the early 90s, serum non-cholesterol sterols were introduced as validated biomarkers for assessing intestina...

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

Cited by 10 publications

References 26 publications

Non-Cholesterol Sterol Concentrations as Biomarkers for Cholesterol Absorption and Synthesis in Different Metabolic Disorders: A Systematic Review

Non-Cholesterol Sterol Concentrations as Biomarkers for Cholesterol Absorption and Synthesis in Different Metabolic Disorders: A Systematic Review

Relation of cholesterol metabolism to pediatric gallstone disease: a retrospective controlled study

Non-Cholesterol Sterol Concentrations As Biomarkers For Cholesterol Absorption And Synthesis In Different Metabolic Disorders: A Systematic Review

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