Serum Selenium Status as a Diagnostic Marker for the Prognosis of Liver Transplantation

Julian Seelig,Julian Hackler,Johann Pratschke,Qian Sun,Deana Haxhiraj,Raban Arved Heller,Lutz Schomburg,Anika Kästner,Moritz Schmelzle,Safak Gül-Klein,Nils Lachmann

doi:10.3390/nu13020619

Abstract

The trace element selenium (Se) is taken up from the diet and is metabolized mainly by hepatocytes. Selenoprotein P (SELENOP) constitutes the liver-derived Se transporter. Biosynthesis of extracellular glutathione peroxidase (GPx3) in kidney depends on SELENOP-mediated Se supply. We hypothesized that peri-operative Se status may serve as a useful prognostic marker for the outcome in patients undergoing liver transplantation due to hepatocellular carcinoma. Serum samples from liver cancer patients were routinely collected before and after transplantation. Concentrations of serum SELENOP and total Se as well as GPx3 activity were determined by standardized tests and related to survival, etiology of cirrhosis/carcinoma, preoperative neutrophiles, lymphocytes, thyrotropin (TSH) and Child–Pugh and Model for End-Stage Liver Disease (MELD) scores. A total of 221 serum samples from 79 transplanted patients were available for analysis. The Se and SELENOP concentrations were on average below the reference ranges of healthy subjects. Patients with ethanol toxicity-dependent etiology showed particularly low SELENOP and Se concentrations and GPx3 activity. Longitudinal analysis indicated declining Se concentrations in non-survivors. We conclude that severe liver disease necessitating organ replacement is characterized by a pronounced Se deficit before, during and after transplantation. A recovering Se status after surgery is associated with positive prognosis, and an adjuvant Se supplementation may, thus, support convalescence.

Highlights

Several converging pathways contribute to declining serum Se status, in part via reduced biosynthesis of the Se transport protein selenoprotein P (SELENOP) in hepatocytes as part of the negative acute phase response (APR) [4,5,6,7]
A longitudinal study of patients with hepatocellular carcinoma (HCC) that were selected for liver transplantation (LT) was conducted at the Department of Surgery at Charité—Universitätsmedizin Berlin
The analyses indicated that total serum Se was of similar quality as the Model for End-Stage Liver Disease (MELD) score for predicting survival, yielding areas under the curve (AUC) of 65.9% and 64.7%, respectively (Figure 6A)

Summary

Introduction

Several converging pathways contribute to declining serum Se status, in part via reduced biosynthesis of the Se transport protein selenoprotein P (SELENOP) in hepatocytes as part of the negative acute phase response (APR) [4,5,6,7]. Studies in lipopolysaccharide (LPS)-injected mice as a rodent model of APR have indicated that the inflammatory stimulus reduces the transcription of central genes controlling Se metabolism, selenocysteine (Sec) formation and Sec insertion into growing selenoproteins [8,9,10]. An impaired hepatic Se metabolism caused by an APR is associated with decreased SELENOP biosynthesis and secretion, causing a declining Se status in the circulation and in target tissues, as observed, e.g., in sepsis [12], severe trauma [13], inflammatory disease [14] or in COVID-19 [15]

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Discussion

Conclusion