Discovery and validation of urinary metabotypes for the diagnosis of hepatocellular carcinoma in West Africans

Abstract

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 ( 1 H-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 ( 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

Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians

“…These findings were replicated in a larger study from Gambia, Senegal and Nigeria (the PROLIFICA Study). 43 A similar study was conducted to profile serum samples metabolically from patients diagnosed with hepatocellular carcinoma (HCC). 44 Metabolites of interest were focused on impaired lipid metabolism; serum lipid concentration was reduced but acetate, the end product of lipid metabolism, was raised, suggesting accelerated lipid degradation.…”

New technologies – new insights into the pathogenesis of hepatic encephalopathy

“…Metabolic profiling has also been used to investigate the possibility of differentiating hepatocellular carcinoma (HCC) from cirrhosis by analysis of urinary metabolites in order to allow identification and early treatment of patients with HCC in West Africa, where hepatitis B and C prevalence is high (Ladep et al 2014). The study identified six urinary metabolites; acetylcarnitine, betaine aldehyde, carnitine, creatine, ribitol and N-acetylglutamate, which were increased (P < 0.005) with presence and grade of HCC compared to cirrhosis.…”

Prevention of Liver Fibrosis and Cancer in Africa: The PROLIFICA project – a collaborative study of hepatitis B-related liver disease in West Africa

“…To date, the PROLIFICA study has provided important insights into HBV-related HCC in West Africa, including identification of novel metabonomic biomarkers that may prove useful for HCC diagnosis in resource-poor settings; [11,12] identification of genomic determinants of HCC and epidemiological insights into risks for more severe HBVrelated liver disease; [13] validation of point-of-care tests for HBV (manuscript in submission) and the optimal use of the Fibroscan to measure liver stiffness [14] as a surrogate imaging marker for liver fibrosis; and the non-invasive aspartate aminotransferase-to-platelet ratio (APRI score) to determine the severity of liver cirrhosis from simple blood tests (manuscript in submission).…”