Urinary Metabotyping of Hepatocellular Carcinoma in a UK Cohort Using Proton Nuclear Magnetic Resonance Spectroscopy
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Accepted version
Author(s)
Type
Journal Article
Abstract
Background: Discriminatory metabolic profiles have been described in urinary 1H nuclear magnetic resonance (NMR) spectroscopy studies of African patients with hepatocellular carcinoma (HCC). This study aimed to assess similarities in a UK cohort, where there is a greater etiological diversity. Methods: Urine from cirrhosis and HCC patients was analyzed using a 600MHz 1H NMR system. Multivariate analysis and median group MR spectra comparison identified metabolite alterations between groups. Metabolite identification was achieved through literature reference and statistical total correlation spectroscopy. Diagnostic accuracy was compared to serum alpha-fetoprotein (AFP). Results: Of the 52 patients recruited, 13 samples from HCC and 25 from cirrhosis patients were selected. At 200IUmL-1, diagnostic sensitivity of AFP was 27%. Multivariate analysis of urinary spectra generated diagnostic models with a sensitivity/specificity of 53.6%/96%. p-Cresol sulfate (P =0.04), creatinine (P =0.03), citrate (P =0.21) and hippurate (P =0.52) were reduced in the HCC patients. Carnitine (P =0.31) and formate (P =0.44) were elevated. Conclusion: Diagnostic sensitivity was lower than previous African studies, but still outperformed serum AFP. Reduced creatinine, citrate and hippurate and elevated carnitine are comparable with the African studies. p-Cresol sulfate alteration is a novel finding and may indicate an altered sulfonation capacity of the liver in patients with HCC.
Date Issued
2016-04-20
Date Acceptance
2016-03-20
Citation
Journal of Clinical and Experimental Hepatology, 2016, 6 (3), pp.186-194
ISSN
2213-3453
Publisher
Elsevier
Start Page
186
End Page
194
Journal / Book Title
Journal of Clinical and Experimental Hepatology
Volume
6
Issue
3
Copyright Statement
© 2016 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
British Liver Trust
Trustees of the London Clinic
Grant Number
N/A
N/A
Subjects
1H NMR
1H NMR, proton nuclear magnetic resonance
AFP, alpha-fetoprotein
ALT, alanine transaminase
BCLC, Barcelona Clinic Liver Cancer
BMI, body mass index
HBV, hepatitis B virus
HCC, hepatocellular carcinoma
HCV, hepatitis C virus
HIV, human immunodeficiency virus
INR, International Normalized Ratio
NASH, non-alcoholic steatohepatitis
PCA, principal component analysis
PLS-DA, partial least squares discriminant analysis
SEER, surveillance Epidemiology and End Results
STOCSY, statistical total correlation spectroscopy
TSP, trimethyl-silyl phosphate
US, ultrasonography
biomarkers
hepatocellular carcinoma
metabonomics
Publication Status
Published