Few studies are available on metabolic changes in liver injuries and this is the first metabolomic study evaluating a group of HCV-positive patients, before and after viral eradication via DAA IFN-free regimens, using 1H-NMR to characterize and compare their serum fingerprints to naïve HBV-patients and healthy donors. The investigation clearly shows differences in the metabolomic profile of HCV patients before and after effective DAA treatment. Significant changes in metabolites levels in patients undergoing therapy suggest alterations in several metabolic pathways. It has been shown that 1H-NMR fingerprinting approach is an optimal technique in predicting the specific infection and the healthy status of studied subjects (Monte-Carlo cross validated accuracies: 86% in the HCV vs HBV model, 98.7% in the HCV vs HC model). Metabolite data collected support the hypothesis that the HCV virus induces glycolysis over oxidative phosphorylation in a similar manner to the Warburg effect in cancer, moreover our results have demonstrated a different action of the two viruses on cellular metabolism, corroborating the hypothesis that the metabolic perturbation on patients could be attributed to a direct role in viral infection. This metabolomic study has revealed some alteration in metabolites for the first time (2-oxoglutarate and 3-hydroxybutrate) concerning the HCV-infection model that could explain several extrahepatic manifestations associated with such an infection.

BACKGROUND and AIMSDirect acting antivirals (DAAs) usually lead to improvement/remission of cryoglobulinemic vasculitis (CV) although symptoms may persist/recur after a sustained virological response (SVR). We evaluated haematological and genetic markers in HCV-SVR vasculitis patients with and without persisting/recurring symptoms to early predict the CV outcome. APPROACH and RESULTSNinety-eight HCV-CV patients were prospectively enrolled after a DAA-induced SVR:Group A: 52 with complete clinical response; Group B: 46 with symptom maintenance/recurrence. Monoclonal B-cell lymphocytosis, t(14;18) translocation and abnormal free light chains k/λ ratios were detected by flow-cytometry or nested-PCR or nephelometry in 4% Group A vs 17% Group B (p= 0.04) patients, 17% Group A vs 40% Group B patients (p= 0.02) and 17% Group A vs 47% Group B (p= 0.003) patients, respectively.At least one out of three clonality markers was altered/positive in 29% of Group A vs 70% of Group B patients (p<0.0001).When available, pre-therapy samples were also tested for t(14;18) translocation (detected in 12/37 (32%) Group A and 21/38 (55%) Group B) and k/λ ratios (abnormal in 5/35 (14%) Group A and 20/38 (53%) Group B) (p=0.0006), while at least one clonality marker was detected/altered in 16/37 (43%) Group A and 30/38 (79%) Group B (p=0.002).CV-associated single nucleotide polymorphisms were tested by Real-Time PCR. Amongst them, notch4 rs2071286 T minor allele and TT genotype showed a higher frequency in Group B vs Group A (46% vs 29%, p=0.01 and 17% vs 2%, p=0.006, respectively). CONCLUSIONHematological or genetic analyses could be used to foresee the CV clinical response after DAA-therapy and could be valuable to assess a rational flow-chart to manage CV during the follow-up.

Longitudinal evaluation of liver stiffness and outcomes in patients with chronic hepatitis C before and after short-and long-term IFN-free antiviral treatment.

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