Dataset Information

Low PCSK9 levels are correlated with mortality in patients with end-stage liver disease.

ABSTRACT: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in the cholesterol metabolism and is synthesized by the liver. It interacts with the LDL-receptor to promote its degradation. The model of end-stage liver disease (MELD) score is a well-established tool to estimate the risk of mortality in patients with end-stage chronic liver disease. The study aims to assess the associations between PCSK9, hypocholesterinemia, liver synthesis, cholestasis, MELD score and mortality in patients with end-stage liver disease.Serum samples were obtained from 74 patients with severe liver disease. The study participants were aged between 23 and 70 y (mean: 55.8 y; 47 males [63.5%], 27 females [36.5%]). Samples were selected from those with a wide range of MELD scores (7 to 40). Patients that underwent liver transplantation (17 / 74) were censored at the time of transplantation for mortality analysis.PCSK9 values ranged from 31.47 ng/mL to 261.64 ng/mL. The median value was 106.39 ng/ml. PCSK9 was negatively correlated with markers of liver function and cholestasis (INR, bilirubin). Over a 90-d follow-up, 15 of 57 (26,3%) patients died within the 90-d follow-up without receiving liver transplantation. Thirteen of 31 (42%) patients with PCSK9 levels below the median died compared to 2/26 (8%) patients with higher PCSK9 levels (p = 0.006). In this cohort, there were no significant correlations between PCSK9, cholesterol, its precursors and several phytosterols.Low PCSK9 serum concentrations were associated with higher mortality in patients with end-stage liver disease. The mean PCSK9 levels in the study population were much lower than those found in normal or healthy populations. Further studies are required to acquire a more detailed understanding of the role of PCSK9 in liver-related mortality.

SUBMITTER: Schlegel V

PROVIDER: S-EPMC5519179 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Low PCSK9 levels are correlated with mortality in patients with end-stage liver disease.

Schlegel Valentin V Treuner-Kaueroff Theresa T Seehofer Daniel D Berg Thomas T Becker Susen S Ceglarek Uta U Thiery Joachim J Kaiser Thorsten T

PloS one 20170720 7

<h4>Introduction</h4>Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in the cholesterol metabolism and is synthesized by the liver. It interacts with the LDL-receptor to promote its degradation. The model of end-stage liver disease (MELD) score is a well-established tool to estimate the risk of mortality in patients with end-stage chronic liver disease. The study aims to assess the associations between PCSK9, hypocholesterinemia, liver synthesis, cholestasis, MELD score an ...[more]

PMID: 28727814

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Project description:Donor livers are offered to patients with the highest risk of death. How ascites could inform risk models to reduce liver transplant wait-list mortality is unclear. All adult candidates for primary liver transplantation for cirrhosis without exception points who were registered with the Organ Procurement and Transplantation Network from 2005 to 2007 composed our study cohort. Using Cox models and advanced discriminative metrics and paying attention to geographic disparities, we evaluated the additional risk discrimination of moderate ascites over that of the Model for End-Stage Liver Disease (MELD) or the Model for End-Stage Liver Disease plus serum sodium (MELD-Na) alone for the prediction of 90-day wait-list mortality. Additional analyses examined lower mortality risk candidates and those listed in high-demand, low-supply United Network for Organ Sharing regions in which accounting for ascites may most significantly affect wait-list mortality. Between 2005 and 2007, 18,124 subjects were listed for liver transplantation. Mortality was higher in patients with moderate ascites (15.4% versus 6.0%, P < 0.0001), and this risk persisted despite adjustments for MELD (hazard ratio = 1.58, 95% confidence interval = 1.42-1.76) and MELD-Na (hazard ratio = 1.42, 95% confidence interval = 1.28-1.58). The effect of moderate ascites was more prominent with a MELD score <21 (equal to 4.7 MELD units) or with a MELD-Na score <21 (equal to 3.5 MELD-Na units). Wait-list mortality was higher in patients with moderate ascites who were listed in high-demand, limited-supply regions (25.8% versus 17.5% at 1 year, P < 0.01). With the addition of moderate ascites, there was improvement in the overall risk model, particularly with a MELD score <21, as measured by the C index and integrated discrimination improvement. Moderate ascites informed risk prediction, particularly with a MELD score <21 and in high-demand, limited-supply regions. Under the MELD system, the presence of moderate ascites should prompt clinicians to consider strategies to expand access to transplantation, such as the use of extended donor liver grafts.

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Dataset Information

Low PCSK9 levels are correlated with mortality in patients with end-stage liver disease.

Publications

Low PCSK9 levels are correlated with mortality in patients with end-stage liver disease.

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