Serum Metabolic Profiling of Advanced Cirrhosis Based on HCV

Abstract

Background: Cirrhosis is recognized by a reduction in hepatocyte proliferation with an increase in fibrous tissue, which may ultimately lead to the development of cancerous nodules. Liver biopsy has remained the gold standard for confirming liver fibrosis stages, but there are not any nonreversible and specific therapeutic targets in advanced cirrhosis. In the present study, we used the NMR method to find potential therapeutic markers in serum of HCV -cirrhotic patients with advanced stage.Methods: A metabolic profiling study was conducted using 2 groups: decompensated HCV-cirrhosis patients (n = 21) and healthy controls (n = 18). 1H nuclear magnetic resonance (NMR) approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by the multivariate principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Moreover, metabolic pathways were determined using MetaboAnalyst 3.0.Results: Specifically, 16 metabolites showed alteration between the 2 groups. Compared with healthy controls, a number of metabolites showed increased concentration in serum of decompensated HCV-cirrhosis such as succinic acid, isovaleraldehyde, citrulline, propanal and cinnamaldehyde, while several others were observed in decreased levels in the decompensated HCV-cirrhosis such as valine, glutamine, trimethylamine, lactate, proline, aspartate, lipid, VLDL, isoleucine, fucose, and glutamate. Aminoacyl-tRNA biosynthesis, alanine, aspartate, glutamate metabolism and arginine, and proline metabolism are the most significant pathways associated with advanced HCV-cirrhosis. Conclusions:Metabolomic profiling through NMR can identify the metabolic disturbances in advanced HCV-cirrhosis. Aberrant amino acid biosynthesis may be the hallmark with increasing severity of cirrhosis as well as alterations in energetic metabolism.

Integrated liver and serum proteomics uncover sexual dimorphism and alteration of several immune response proteins in an aging Werner syndrome mouse model

“…The results are also consistent with the low systemic but chronic inflammation observed in Werner syndrome patients [6,39]. More interestingly, increased expression of the immunoglobulin variants IGKC and IGHM has been associated with NAFLD as well as liver fibrosis and cirrhosis in human subjects [40][41][42][43]. Although analyses on the activation status of the immune cells in Wrn Δhel/Δhel mice compared to age-matched wild type mice are required, the measurements of several serum cytokines in the mouse cohorts have indicated an increase of IL-5 in both females and males at ten months of age compared to four months old groups of mice.…”

Predictive value of serum amino acids as metabolite biomarkers in cirrhosis: a systematic review and meta-analysis

“…Of the remaining 83 studies, 64 studies were excluded due to not include full text, conference abstracts, duplicate data, incomplete information, and did not meet inclusion criteria. Finally, 19 studies were included for qualitative summaries (Huang et al [28] , 2021; Xie et al [29] , 2020; Kim et al [8] , 2019; Yoo et al [30] , 2019; Zhao et al, 2018; Safaei et al [15] , 2017; Hao et al [19] , 2017; Dabos et al [17] , 2015; Bell et al [12] , 2015; Fitian et al [13] , 2014; Liu et al [20] , 2014; Qi et al [16] , 2012; Jiménez et al [14] , 2010; Gao et al [18] , 2009; Gao et al [9] , 2019; Ye et al [31] , 2017; Yang et al [32] , 2017; Kong et al [10] , 2016; Wang et al [11] , 2015) with 2073 participants (831 in the cirrhosis group and 1242 in the healthy control group). Of these 19 studies, 5 studies which reported amino acid speci c concentrations and were evaluated as high quality studies based on NOS scales were meta-analyzed (Xie et al [29] , 2020; Kim et al [8] , 2019; Gao et al [9] , 2019; Kong et al [10] , 2016; Dabos et al [17] , 2015), including 818 participants (214 in the cirrhosis group and 604 in the healthy control group).The ow chart is shown in Fig.…”

“…8 studies reported disease stage in 296 cirrhotic patients (35.62%). 3 studies (Huang et al [28] , 2021; Safaei et al [15] , 2017; Yang et al [32] , 2017) with a total of 151 cirrhotic patients, including 27 compensated (17.88%) and 124 decompensated (82.12%). 5 studies (Kim et al [8] , 2019; Hao et al [19] , 2017; Dabos et al [17] , 2015; Wang et al [11] , 2015; Fitian et al [13] , 2014) were staged by Child-Pugh score.…”

“…Quality was generally high, with 15 studies equal to or more than 7 stars due to better assessment of study population selection, comparability between groups, and measured exposure factors. The other 4 studies yielded 6 stars because of inadequate case de nition or poor control of confounding between cases and controls (Zhao et al [33] , 2018; Safaei et al [15] , 2017; Bell et al [12] , 2015; Gao et al [18] , 2009). The risk of bias results for the included studies are shown in Table 1.…”

“…Andrea et al [7] found signi cant changes in serum alanine, 1-methylhistidine, glutamine, valine and lysine levels in patients with early and late stage hepatocellular carcinoma. Metabolomics techniques used to determine serum or plasma metabolite levels include liquid chromatography-mass spectrometry (LC-MS) [8][9][10] , gas chromatography-mass spectrometry(GC-MS) [11][12][13] , and 1 H-nuclear magnetic resonance spectroscopy ( 1 H-NMR) [14][15][16][17][18][19][20] .…”