The metabolism of cholestanol in primary biliary cirrhosis

Gylling, Helena; Vuoristo, Matti; Färkkilä, Martti; Tatu, A.Miettinen

doi:10.1016/s0168-8278(96)80165-6

Cited by 25 publications

(38 citation statements)

References 25 publications

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“…This relationship was also clear in end-stage PBC, but not as consistent as in ALF, as high serum cholestanol (ratios) indicated low ratios of only lathosterol/bilirubin and campesterol/sitosterol. Accordingly, our results are in accordance with earlier studies among PBC-patients, which showed that hypercholestanolemia and accumulation of cholestanol in tissues develop gradually during worsening state of PBC [10,11,15,16].…”

Section: Discussionsupporting

confidence: 93%

“…Elevated post-LTX cholestanol ratio among PBC-patients should be further evaluated by a long-term follow-up study, which would include liver histology. Overall, although the most probable reason to hypercholestanolemia in PBC is cholestasis, analysis of biliary and fecal sterols in PBC-patients indicated that also hepatic cholestanol synthesis is modestly increased in PBC for an unknown reason [11]. Interestingly, our present results showed consistently a close positive relation of serum cholestanol ratios to bilirubin except pre-LTX in the ALFgroup, of which the latter finding is probably due to low hepatic synthesis of cholestanol among these patients.…”

Section: Discussionsupporting

confidence: 49%

“…This gives an intriguing option, first, to seek predictive non-cholesterol sterol markers for, e.g., severe liver failure and poor prognosis, and, second, to evaluate the role of non-cholesterol sterols in hepatic pathophysiology prior to and after liver transplantation (LTX). Studies on primary biliary cirrhosis (PBC), a chronic cholestatic autoimmune liver disease of unknown etiology and among the most common liver diseases leading to LTX [9], suggest that low serum ratios of lathosterol/ cholesterol and campesterol/sitosterol, but high ratios of cholestanol/cholesterol reflect advanced PBC [10,11]. Acute liver failure (ALF) is defined by the rapid development of hepatic synthetic dysfunction associated with significant coagulopathy and hepatic encephalopathy [12,13], of which the etiology is indeterminate in 17-43% of cases [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, assessment of the latter provides a link between cholesterol metabolism and liver function [2][3][4][5]. Furthermore, serum cholestanol/cholesterol is even a more sensitive marker of cholestasis among early-stage PBC-patients than serum bilirubin [10,11]. Precursor sterols of cholesterol biosynthesis, e.g., lathosterol, serve as serum surrogate markers of cholesterol synthesis [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…These liver diseases were chosen, because they both represent a cholestatic liver failure, and because serum sterol profiles and cholesterol metabolism of ALF of unknown etiology have not been elucidated so far. In this respect, PBC-patients have been studied most widely [10,11,15,16], and PBC is one of the commonest indications for LTX in Finland; thus, they form a suitable reference group and study population of sufficient size. The following hypotheses were tested: (I) patients with ALF and PBC have differential patterns in their serum sterols and sterol metabolism before and after LTX [10,15], (II) certain profiles of serum sterols are related to poor liver function prior to LTX [15,16], and (III) ALF can be caused by abnormal sterol metabolism [17].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Nikkilä

Nissinen

Gylling

et al. 2008

Journal of Hepatology

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Nikkilä

Nissinen

Gylling

et al. 2008

Journal of Hepatology

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Noncholesterol Sterols as Surrogate Markers in Patients with Severe Alcoholic Hepatitis

Sahlman

Nissinen

Simonen

et al. 2018

Lipids

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Severe alcoholic hepatitis (AH) is a life-threatening condition lacking good serologic markers to tailor treatment and predict recovery. We examined the cholesterol metabolism in severe AH to explore prognostic markers and evaluate the profile of cholesterol precursors, cholestanol and phytosterols, in this context. We assessed serum cholesterol, cholesterol precursors, cholestanol, phytosterols, and biochemical markers in 24 patients with severe AH treated with prednisolone and randomized to ciprofloxacin in the ratio 1:1. Response to prednisolone was assessed with the Lille model. Evaluations were made between responders and nonresponders to corticosteroid treatment and during follow-up for 180 days. The findings were compared with those from patients with primary sclerosing cholangitis (PSC) (n = 156) and healthy individuals (n = 124). Responders to prednisolone had ~56-60% higher (p-value 0.032-0.044) serum ratios to cholesterol of phytosterols, while the lathosterol/campesterol ratio was ~76% (p = 0.031) lower compared to nonresponders. Stigmasterol/cholesterol predicted response to corticosteroid therapy. Surrogate markers of cholesterol synthesis (lathosterol and desmosterol) inversely reflected those of absorption (cholestanol and phytosterols) in PSC and controls (r-range -0.247 to -0.559, p < 0.01 for all), contrary to AH patients, among whom this reciprocal regulation was partially recovered on day 90 (lathosterol: r-range -0.733 to -0.952, p < 0.05 for all). AH patients had ~26% lower lathosterol/cholesterol, but 1.13-3.87-fold higher cholestanol/cholesterol and sitosterol/cholesterol compared to control groups (p < 0.05 for all). Median ferritin concentration at baseline was ~37% lower (p = 0.011) among the responders. Cholesterol precursors and phytosterols have a disease-specific profile in AH. Phytosterols and ferritin may serve as surrogate markers for short-term response.

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

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.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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The metabolism of cholestanol in primary biliary cirrhosis

Cited by 25 publications

References 25 publications

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

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

Noncholesterol Sterols as Surrogate Markers in Patients with Severe Alcoholic Hepatitis

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

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