Different metabolic fingerprints between HCV and HBV patients: a possible interference of the two major hepatitis viruses in basal metabolism pathways.

Metabolomics is the study of metabolic changes in biological systems and may identify specific profiles associated with subtle alterations induced by diseases. Studies performing a comparative evaluation of HCV and HBV patients are lacking. HCV can be completely eradicated by direct acting antivirals (DAAs). The aim of this study was to evaluate through NMR-based metabo- lomic approach a group of HCV-positive patients before and after viral eradication by DAA IFN-free regimens, comparing their fingerprints to naive HBV-patients and healthy donors. Methods: Sera were collected before therapy (baseline), at SVR12, and SVR24 time-points, from 67 HCV patients successfully treated with IFN-free DAA regimens; as controls, we tested serum samples from 50 naive subjects with chronic HBV infection (pathological controls; HBV) and 43 healthy donors (healthy controls; HC). Samples were analyzed using proton nuclear magnetic resonance spectroscopy (H-NMR). Results: MPLS analysis of HCV sera showed a significant pair-wise discrimination by comparing SVR12 and SVR24 with baseline samples (with 90% and 82% of accuracy, respectively), indicating that a metabolic efficacy was evident already at SVR12. Metabolic fingerprinting was able to distinguish the study groups (HBV, HCV and healthy subjects) with a 75% accuracy. Also, 34 metabolites emerged from the analysis, some of them significantly differed between HCV group and HS and between HCV group and HBV group (i. e. 2-oxoglutarate, 3-hydroxybutyrate, creatine, choline, valine, alanine, acetate, tyrosine, phenylalanine, formate). In detail, 2-oxoglutarate levels progressively decreased in HCV patients from baseline to SVR24 and its levels were significantly higher in these patients compared to HC and to HBV-subjects. Conclusion: H-NMR proved a significant discrimination for all groups (HCV-baseline, SVR12, SVR24, naïve HBV, HC) and the fingerprints of HCV patients after SVR progressively approached to the ones recorded in HC. Also, fingerprints of untreated HCV and HBV patients can be discriminated with a high accuracy even in the unsupervised analysis, indicating the existence of virus-specific interactions with different metabolic pathways. Finally, a direct role of HCV in altering basal metabolism pathways could help to explain the association with some extrahepatic disease; i. e. previous works reported high levels of 2-oxoglutarate in serum of patients with heart failure and, in this light, our finding could explain the relationship between HCV and an increased risk of cardiovascular disease.