Abstract
BackgroundHigh-throughput technologies have the potential to identify non-invasive biomarkers of liver pathology and improve our understanding of basic mechanisms of liver injury and repair. A metabolite profiling approach was employed to determine associations between alterations in serum metabolites and liver histology in patients with chronic hepatitis C virus (HCV) infection.MethodsSera from 45 non-diabetic patients with chronic HCV were quantitatively analyzed using 1H-NMR spectroscopy. A metabolite profile of advanced fibrosis (METAVIR F3-4) was established using orthogonal partial least squares discriminant analysis modeling and validated using seven-fold cross-validation and permutation testing. Bioprofiles of moderate to severe steatosis (≥33 %) and necroinflammation (METAVIR A2-3) were also derived. The classification accuracy of these profiles was determined using areas under the receiver operator curves (AUROCSs) measuring against liver biopsy as the gold standard.ResultsIn total 63 spectral features were profiled, of which a highly significant subset of 21 metabolites were associated with advanced fibrosis (variable importance score >1 in multivariate modeling; R2 = 0.673 and Q2 = 0.285). For the identification of F3–4 fibrosis, the metabolite bioprofile had an AUROC of 0.86 (95 % CI 0.74–0.97). The AUROCs for the bioprofiles for moderate to severe steatosis were 0.87 (95 % CI 0.76–0.97) and for grade A2–3 inflammation were 0.73 (0.57–0.89).ConclusionThis proof-of-principle study demonstrates the utility of a metabolomics profiling approach to non-invasively identify biomarkers of liver fibrosis, steatosis and inflammation in patients with chronic HCV. Future cohorts are necessary to validate these findings.Electronic supplementary materialThe online version of this article (doi:10.1186/s40169-016-0109-2) contains supplementary material, which is available to authorized users.
Highlights
High-throughput technologies have the potential to identify non-invasive biomarkers of liver pathol‐ ogy and improve our understanding of basic mechanisms of liver injury and repair
Participants were divided into three groups based on liver histopathology characteristics of fibrosis, necroinflammation and steatosis (Table 1)
One-third of the patients were scored with F3–4 fibrosis; 13 and 42 % had moderate to severe steatosis and inflammation, respectively
Summary
High-throughput technologies have the potential to identify non-invasive biomarkers of liver pathol‐ ogy and improve our understanding of basic mechanisms of liver injury and repair. A metabolite profiling approach was employed to determine associations between alterations in serum metabolites and liver histology in patients with chronic hepatitis C virus (HCV) infection. Chronic HCV carriers are at risk of progressive liver fibrosis, and up to 30 % can develop cirrhosis after decades of infection with significant risk of morbidity and mortality. Hepatic fibrosis occurs in the setting of liver injury from immune mediated chronic inflammation and hepatocyte cell turnover. This can lead to cirrhosis, manifested by architectural distortion of the liver and nodule formation [2]. The currently approved antiviral therapy is recommended in all patients with advanced fibrosis or cirrhosis who have the highest risk of HCV-related complications such as liver failure and hepatocellular carcinoma. Especially the diagnosis of cirrhosis, is needed in clinical practice to determine the urgency and need for anti-HCV antiviral therapy [5, 6]
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