Metabolic Phenotyping for Enhanced Mechanistic Stratification of Chronic Hepatitis C-Induced Liver Fibrosis

Sands, Caroline; Guha, Indra Neil; Kyriakides, Michael; Wright, Mark; Beckonert, Olaf; Holmes, Elaine; Rosenberg, William; Coen, Muireann

doi:10.1038/ajg.2014.370

Cited by 35 publications

(24 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study, serum LDL in both the SMFY and GMFS group were dramatically decreased, with an approximately 0.9-fold change in comparison with the control group, revealing that EA at SMFY acupoints and GMFS acupoints may lower cholesterol and slow the conversion from cholesterol to LDL and therefore help to provide potential prevention and treatment for cardiovascular diseases such as hypercholesterolemia and atherosclerosis. Furthermore, an increased severity of liver fibrosis has been reported to be associated with higher tyrosine, phenylalanine, methionine, citrate, and LDL 41 . EA stimulations at the SMFY and GMFS acupoints can lower phenylalanine, LDL, and citrate levels, resulting in an increased capacity for citrate clearance in cirrhotic patients and a lower rate of lipogenesis.…”

Section: Discussionmentioning

confidence: 99%

1H NMR-based Investigation of Metabolic Response to Electro-Acupuncture Stimulation

Lin

Wei

Cheng

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Acupuncture is a traditional Chinese medicine therapy that has been found useful for treating various diseases. The treatments involve the insertion of fine needles at acupoints along specific meridians (meridian specificity). This study aims to investigate the metabolic basis of meridian specificity using proton nuclear magnetic resonance (1H NMR)-based metabolomics. Electro-acupuncture (EA) stimulations were performed at acupoints of either Stomach Meridian of Foot-Yangming (SMFY) or Gallbladder Meridian of Foot-Shaoyang (GMFS) in healthy male Sprague Dawley (SD) rats. 1H-NMR spectra datasets of serum, urine, cortex, and stomach tissue extracts from the rats were analysed by multivariate statistical analysis to investigate metabolic perturbations due to EA treatments at different meridians. EA treatment on either the SMFY or GMFS acupoints induced significant variations in 31 metabolites, e.g., amino acids, organic acids, choline esters and glucose. Moreover, a few meridian-specific metabolic changes were found for EA stimulations on the SMFY or GMFS acupoints. Our study demonstrated significant metabolic differences in response to EA stimulations on acupoints of SMFY and GMFS meridians. These results validate the hypothesis that meridian specificity in acupuncture is detectable in the metabolome and demonstrate the feasibility and effectiveness of a metabolomics approach in understanding the mechanism of acupuncture.

show abstract

Section: Discussionmentioning

confidence: 99%

1H NMR-based Investigation of Metabolic Response to Electro-Acupuncture Stimulation

Lin

Wei

Cheng

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…44 Other areas of interest at high magnetic field strength have been in biomarker development for cholangiocarcinoma using bile collected at ERCP, non-invasive serum biomarkers of fibrosis development in chronic hepatitis C and prediction of outcome following an episode of acute liver failure using serum and urine. [45][46][47] All these studies were able to delineate disease-specific metabolic profiles which were clearly different from healthy and/or disease controls. The in vitro MRS technique on body fluid samples has a role both in large-scale population-based screening without specific a priori hypotheses and in demonstrating the response of the individual to therapy.…”

Section: Applicationsmentioning

confidence: 99%

Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians

Tognarelli

Dawood

Shariff

et al. 2015

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

Magnetic resonance spectroscopy (MRS) provides a non-invasive 'window' on biochemical processes within the body. Its use is no longer restricted to the field of research, with applications in clinical practice increasingly common. MRS can be conducted at high magnetic field strengths (typically 11-14 T) on body fluids, cell extracts and tissue samples, with new developments in whole-body magnetic resonance imaging (MRI) allowing clinical MRS at the end of a standard MRI examination, obtaining functional information in addition to anatomical information. We discuss the background physics the busy clinician needs to know before considering using the technique as an investigative tool. Some potential applications of hepatic and cerebral MRS in chronic liver disease are also discussed. ( J CLIN EXP HEPATOL 2015;5:320-328) T he biomedical applications of nuclear magnetic resonance (NMR) are twofold: magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). The applications of MRS as a research tool are extremely diverse, encompassing studies on isolated cells, body fluids and perfused organs at high magnetic field strengths in an experimental, laboratory-based setting and also in vivo studies using clinical MR systems. 1 In vivo clinical MRS on whole-body MRI scanners has been used to study the metabolism of well-defined regions of the human body, affording a non-invasive 'metabolic window' on a wide range of biochemical processes in the body, including the composition and function of human organs in vivo. 2 Clinical MRS developments have exploited many of the advances in MRI at the magnetic field strengths now used (typically 1.5-3.0 T) and the use of magnetic field gradients. The sensitivity and spatial resolution of MRS is a limiting factor in vivo, but parallel utilisation of in vitro MR spectroscopy of tissue extracts, body fluids and cell lines at much higher magnetic field strengths (typically 11.7-14.1 T) allows more definitive interpretation of the in vivo data. In this article, we aim to equip the clinician with knowledge of the background physics involved in MRS, so that informed decisions can be made for research studies. NUCLEAR MRSNMR refers to the behaviour of atoms subjected to a magnetic field. The phenomenon was first described in 1946 by Bloch and Purcell. Atoms with an odd mass number such as 1 H, 31 P and 13 C possess the quantum property of ''spin'' and behave as dipoles aligning along the axis of an applied magnetic field (Figure 1). During relaxation following excitation, radiofrequency signals are generated which can be expressed as a frequency spectrum. Hydrogen is the most abundant atom in living organisms and using high power magnetic fields on in vitro samples, high resolution metabolic spectra can be obtained with clearly defined metabolite peaks of small molecules (<2 kDa). NUCLEAR SPIN AND ORIENTATIONSNuclear resonance occurs because the nuclei of at least one of the isotopes of most elements possess a magnetic moment. A magnetic moment arises because the nucleus m...

show abstract

“…More recently, unbiased approaches have been undertaken, including protein[9] and metabolite[10] profiling, with the goal of discovering novel biomarkers that improve the diagnostic accuracy of the currently available tests and provide new insights into mechanisms of disease pathogenesis. The aim of this study was to identify novel serum biomarkers of advanced liver fibrosis (METAVIR fibrosis stage 3 or 4 on liver biopsy) using multiplex ELISA-profiling, including cytokines, chemokines, and matrix remodelling factors, in a mixed etiology cohort of CLD patients with known ELF scores[8]; and to evaluate their diagnostic accuracy using liver biopsy as the reference.…”

Section: Introductionmentioning

confidence: 99%

Multiplex Serum Protein Analysis Identifies Novel Biomarkers of Advanced Fibrosis in Patients with Chronic Liver Disease with the Potential to Improve Diagnostic Accuracy of Established Biomarkers

et al. 2016

View full text Add to dashboard Cite

Background and AimsNon-invasive markers of liver fibrosis are urgently required, especially for use in non-specialist settings. The aim of this study was to identify novel serum biomarkers of advanced fibrosis.MethodsWe performed an unbiased screen of 120 serum analytes including cytokines, chemokines and proteases in 70 patients (35 without fibrosis, 35 with cirrhosis on biopsy), and selected a panel of 44 candidate biomarkers, which were subsequently measured in a mixed-etiology cohort of 432 patients with known serum HA, PIIINP and TIMP1 (which comprise the validated Enhanced Liver Fibrosis (ELF) test). Multivariate logistic regression modelling was used to generate models for the prediction of advanced or significant fibrosis (METAVIR ≥F3 and ≥F2, respectively); in addition to identifying biomarkers of disease activity and steatohepatitis.ResultsSeventeen analytes were significantly differentially expressed between patients with no advanced fibrosis and patients with advanced fibrosis, the most significant being hyaluronic acid (HA) and matrix metalloproteinase (MMP) 7 (p = 2.9E-41 and p = 1.0E-26, respectively). The optimal model for the prediction of advanced fibrosis comprised HA, MMP7, MMP1, alphafetoprotein (AFP) and the AST to platelet ratio index (APRI). We demonstrate enhanced diagnostic accuracy (AUROC = 0.938) compared to a model comprising HA, PIIINP and TIMP1 alone (ELF) (AUROC = 0.898, p<0.0001, De Long’s test).ConclusionsWe have identified novel serum biomarkers of advanced liver fibrosis, which have the potential to enhance the diagnostic accuracy of established biomarkers. Our data suggest MMP7 is a valuable indicator of advanced fibrosis and may play a role in liver fibrogenesis.

show abstract

Metabolic Phenotyping for Enhanced Mechanistic Stratification of Chronic Hepatitis C-Induced Liver Fibrosis

Cited by 35 publications

References 49 publications

1H NMR-based Investigation of Metabolic Response to Electro-Acupuncture Stimulation

1H NMR-based Investigation of Metabolic Response to Electro-Acupuncture Stimulation

Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians

Multiplex Serum Protein Analysis Identifies Novel Biomarkers of Advanced Fibrosis in Patients with Chronic Liver Disease with the Potential to Improve Diagnostic Accuracy of Established Biomarkers

Contact Info

Product

Resources

About