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.