Metabolic Characterization of Advanced Liver Fibrosis in HCV Patients as Studied by Serum 1H-NMR Spectroscopy

Abstract

Several etiologies result in chronic liver diseases including chronic hepatitis C virus infection (HCV). Despite its high incidence and the severe economic and medical consequences, liver disease is still commonly overlooked due to the lack of efficient non-invasive diagnostic methods. While several techniques have been tested for the detection of fibrosis, the available biomarkers still present severe limitations that preclude their use in clinical diagnostics. Liver diseases have also been the subject of metabolomic analysis. Here, we demonstrate the suitability of 1H NMR spectroscopy for characterizing the metabolism of liver fibrosis induced by HCV. Serum samples from HCV patients without fibrosis or with liver cirrhosis were analyzed by NMR spectroscopy and the results were submitted to multivariate and univariate statistical analysis. PLS-DA test was able to discriminate between advanced fibrotic and non-fibrotic patients and several metabolites were found to be up or downregulated in patients with cirrhosis. The suitability of the most significantly regulated metabolites was validated by ROC analysis. Our study reveals that choline, acetoacetate and low-density lipoproteins are the most informative biomarkers for predicting cirrhosis in HCV patients. Our results demonstrate that statistical analysis of 1H-NMR spectra is able to distinguish between fibrotic and non-fibrotic patients suffering from HCV, representing a novel diagnostic application for NMR spectroscopy.

Serum Metabolic Profiling of Advanced Cirrhosis Based on HCV

“…These amino acids are related to intermediate components of TCA cycle, an essential pathway for the amino acids metabolism (26,27). Our results are consistent with those of the previous studies on cirrhosis and liver diseases (28,29). The results of amino acid imbalance on TCA cycle in the serum of patients with advanced cirrhosis can prove the hypothesis of impairment of TCA cycle (30).…”

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

“…Taken together, future experiments are required to address mechanisms through which relative ketogenic insufficiency may become maladaptive, contribute to hyperglycemia, provoke steatohepatitis, and whether these mechanisms are operant in human NAFLD/NASH. As epidemiological evidence suggests impaired ketogenesis during the progression of steatohepatitis (Embade et al, 2016; Marinou et al, 2011; Männistö et al, 2015; Pramfalk et al, 2015; Safaei et al, 2016) therapies that increase hepatic ketogenesis could prove salutary (Degirolamo et al, 2016; Honda et al, 2016). …”

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

“…Glucose, citrate, and VLDL1 were significantly elevated, and choline, glutamine, acetoacetate, glycoprotein N-acetyl groups, cysteine, histidine, and LDL1 were significantly depressed in the serum of cirrhotic HCV patients. The authors believed that these results provided new biomarkers to distinguish no fibrosis from severe fibrosis (cirrhosis) in HCV infection [163]. An investigation of Italian patients with chronic HCV attempted to diagnose the degree of fibrosis using 1 H NMR on plasma, serum, and urine samples.…”