Potential conflict of interest: Nothing to report.
Discovery and validation of urinary metabotypes for the diagnosis of hepatocellular carcinoma in West Africans
Article first published online: 25 AUG 2014
© 2014 by the American Association for the Study of Liver Diseases
Volume 60, Issue 4, pages 1291–1301, October 2014
How to Cite
Ladep, N. G., Dona, A. C., Lewis, M. R., Crossey, M. M.E., Lemoine, M., Okeke, E., Shimakawa, Y., Duguru, M., Njai, H. F., Fye, H. K.S., Taal, M., Chetwood, J., Kasstan, B., Khan, S. A., Garside, D. A., Wijeyesekera, A., Thillainayagam, A. V., Banwat, E., Thursz, M. R., Nicholson, J. K., Njie, R., Holmes, E. and Taylor-Robinson, S. D. (2014), Discovery and validation of urinary metabotypes for the diagnosis of hepatocellular carcinoma in West Africans. Hepatology, 60: 1291–1301. doi: 10.1002/hep.27264
This study was funded by the European Union Framework 7 programme (PROLIFICA: Prevention of Fibrosis and Liver Cancer in Africa). N.G.L. was supported by a fellowship from the Trustees of the London Clinic, London, UK and by the British Medical Research Council ICIC scheme. M.M.E.C. was supported by a fellowship (Halley Stewart Foundation, Cambridge, United Kingdom).
- Issue published online: 22 SEP 2014
- Article first published online: 25 AUG 2014
- Accepted manuscript online: 13 JUN 2014 02:29AM EST
- Manuscript Accepted: 10 JUN 2014
- Manuscript Received: 10 MAR 2014
There is no clinically applicable biomarker for surveillance of hepatocellular carcinoma (HCC), because the sensitivity of serum alpha-fetoprotein (AFP) is too low for this purpose. Here, we determined the diagnostic performance of a panel of urinary metabolites of HCC patients from West Africa. Urine samples were collected from Nigerian and Gambian patients recruited on the case-control platform of the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) program. Urinary proton nuclear magnetic resonance (1H-NMR) spectroscopy was used to metabolically phenotype 290 subjects: 63 with HCC; 32 with cirrhosis (Cir); 107 with noncirrhotic liver disease (DC); and 88 normal control (NC) healthy volunteers. Urine samples from a further cohort of 463 subjects (141 HCC, 56 Cir, 178 DC, and 88 NC) were analyzed, the results of which validated the initial cohort. The urinary metabotype of patients with HCC was distinct from those with Cir, DC, and NC with areas under the receiver operating characteristic (AUROC) curves of 0.86 (0.78-0.94), 0.93 (0.89-0.97), and 0.89 (0.80-0.98) in the training set and 0.81 (0.73-0.89), 0.96 (0.94-0.99), and 0.90 (0.85-0.96), respectively, in the validation cohort. A urinary metabolite panel, comprising inosine, indole-3-acetate, galactose, and an N-acetylated amino acid (NAA), showed a high sensitivity (86.9% [75.8-94.2]) and specificity (90.3% [74.2-98.0]) in the discrimination of HCC from cirrhosis, a finding that was corroborated in a validation cohort (AUROC: urinary panel = 0.72; AFP = 0.58). Metabolites that were significantly increased in urine of HCC patients, and which correlated with clinical stage of HCC, were NAA, dimethylglycine, 1-methylnicotinamide, methionine, acetylcarnitine, 2-oxoglutarate, choline, and creatine. Conclusion: The urinary metabotyping of this West African cohort identified and validated a metabolite panel that diagnostically outperforms serum AFP. (Hepatology 2014;60:1291–1301)