Liver Cirrhosis Patients Who Had Normal Liver Function Before Liver Cirrhosis Development Have the Altered Metabolic Profiles Before the Disease Occurrence Compared to Healthy Controls

Abstract

Liver cirrhosis (LC) is the final usual outcome of liver damage induced by various chronic liver diseases. Because of asymptomatic nature of LC, it is usually diagnosed at late and advanced stages, and patients are easy to miss the best timing for treatment. Thus, the early detection of LC is needed. In the prospective Korean Cancer Prevention Study-II (K-II), we aimed to identify valuable biomarkers for LC using metabolomics to distinguish subjects with incident LC (LC group) from subjects free from LC (control group) during a mean 7-year follow-up period. Metabolic alterations were investigated using baseline serum specimens acquired from 94 subjects with incident LC and 180 age- and sex-matched LC-free subjects via ultra-performance liquid chromatography (UPLC)-linear-trap quardrupole (LTQ)-Orbitrap mass spectrometry (MS). As a result of the metabolic analysis, 46 metabolites were identified. Among them, 11 and 18 metabolite level showed a significant increase and decrease, respectively, in the LC group compared to the control group. Nine metabolic pathways, including glyoxylate and dicarboxylate metabolism, amino acid metabolism, fatty acid metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism, were significantly different between the two groups. Logistic regression demonstrated that the LC emergence was independently affected by serum levels of myristic acid, palmitic acid, linoleic acid, eicosapentaenoic acid (EPA), lysophosphatidic acid (LPA) (18:1), glycolic acid, lysophosphatidylcholine (lysoPC) (22:6), and succinylacetone (R2 = 0.837, P < 0.001). This prospective study revealed that dysregulation of various metabolism had the clinical relevance on the LC development. Moreover, myristic acid, palmitic acid, linoleic acid, EPA, LPA (18:1), glycolic acid, lysoPC (22:6), and succinylacetone were emerged as independent variables influencing the incidence of LC. The results support that the early biomarkers found in this study may useful for predicting and remedying the risk of LC.

Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review

“…Considering mounting evidence supported that long-term complications can be prevented by optimizing metabolic control, we recommend an aggressive therapy for GSD VI [30]. Systematic follow-up and specific biomarkers are also needed to monitor this silent course although the improvement of elevated transaminase was observed in most of our patients with GSD VI [15,33]. Kobayashi et al concluded that variants with an allele frequency higher than 0.01% in the ExAC database were generally already well characterized in the literature as known founder mutations [34].…”

Common Transcriptional Program of Liver Fibrosis in Mouse Genetic Models and Humans

“…Bile acids are an example of a potential common serum biomarker of liver diseases. A potential prognostic biomarker was identified by a metabolomics prospective study where serum fatty acids, including linoleic and α-linoleic acids, were lower before the occurrence of cirrhosis in patients in comparison to healthy controls [ 25 ]. The observed model-specific changes in transcriptome signatures could reflect the unique metabolic rearrangements among fibrotic models ( Figure 6 ).…”

The Mechanism of Increased Intestinal Palmitic Acids Absorption and The Impact On Hepatic Stellate Cell Activation in Non-Alcoholic Steatohepatitis

“…Activated HSCs are known to enhance the expression of TGF-β, COL1A1, α-SMA, TIMP, and PAI-1, which are involved in liver brosis [33][34][35][36][37][38] . Previous studies have shown that blood PA concentrations in cirrhotic patients are associated with the degree of liver brosis and that PA concentrations were high even before the onset of cirrhosis 39,40 . We showed that intestinal PA absorption and PA concentration in portal blood were increased in NASH rats.…”