Hepatitis C virus (HCV) infection induces a long-term inflammatory response and oxidative-stress in the liver microenvironment, leading to hepatic fibrosis and metabolic alterations. Direct-acting-antiviral-agents (DAAs) induce HCV-clearance, even though liver damage is only partially restored. In this context, understanding the impact of viral-eradication on liver metabolic activities could allow optimizing the metabolic care of the patient. The present prospective longitudinal study aims at characterizing the urinary metabolic profile of HCV-induced severe liver fibrosis and the metabolic changes induced by DAAs and HCV-clearance by nuclear magnetic resonance-based metabolomics. The urinary metabolic profile of 23 HCV males with severe liver fibrosis and 20 age-matched healthy-controls was analyzed by NMR-based-metabolomics before starting DAAs, at the end-of-therapy, after one and three months of follow-up. The urinary metabolic profile of patients with severe liver fibrosis was associated to pseudouridine, hypoxanthine, methylguanidine and dimethylamine, highlighting a profile related to oxidative damage, and to tyrosine and glutamine, related to a decreased breakdown of aromatic aminoacids and ammonia detoxification, respectively. 1-methylnicotinamide, a catabolic intermediate of nicotinamide-adenine-dinucleotide, was significantly increased in HCV-patients and restored after HCV-clearance, probably due to the reduced hepatic inflammation. 3-hydroxy-3-methylbutyrate, an intermediate of leucine-catabolism which was permanently restored after HCV-clearance, suggested an improvement of skeletal muscle protein synthesis. Finally, 3-hydroxyisobutyrate and 2,3-dihydroxy-2-methylbutyrate, intermediates of valine-catabolism, glycine and choline increased temporarily during therapy, resulting as potential biomarkers of DAAs systemic effects.

Urinary metabolomics of HCV patients with severe liver fibrosis before and during the sustained virologic response achieved by direct acting antiviral treatment / Biliotti, Elisa; Giampaoli, Ottavia; Sciubba, Fabio; Marini, Federico; Tomassini, Alberta; Palazzo, Donatella; Capuani, Giorgio; Esvan, Rozenn; Spaziante, Martina; Taliani, Gloria; Miccheli, Alfredo. - In: BIOMÉDECINE & PHARMACOTHÉRAPIE. - ISSN 0753-3322. - 143:(2021), pp. 1-12. [10.1016/j.biopha.2021.112217]

Urinary metabolomics of HCV patients with severe liver fibrosis before and during the sustained virologic response achieved by direct acting antiviral treatment

Biliotti, Elisa;Giampaoli, Ottavia;Sciubba, Fabio;Marini, Federico;Tomassini, Alberta;Palazzo, Donatella;Capuani, Giorgio;Esvan, Rozenn;Spaziante, Martina;Taliani, Gloria;Miccheli, Alfredo
2021

Abstract

Hepatitis C virus (HCV) infection induces a long-term inflammatory response and oxidative-stress in the liver microenvironment, leading to hepatic fibrosis and metabolic alterations. Direct-acting-antiviral-agents (DAAs) induce HCV-clearance, even though liver damage is only partially restored. In this context, understanding the impact of viral-eradication on liver metabolic activities could allow optimizing the metabolic care of the patient. The present prospective longitudinal study aims at characterizing the urinary metabolic profile of HCV-induced severe liver fibrosis and the metabolic changes induced by DAAs and HCV-clearance by nuclear magnetic resonance-based metabolomics. The urinary metabolic profile of 23 HCV males with severe liver fibrosis and 20 age-matched healthy-controls was analyzed by NMR-based-metabolomics before starting DAAs, at the end-of-therapy, after one and three months of follow-up. The urinary metabolic profile of patients with severe liver fibrosis was associated to pseudouridine, hypoxanthine, methylguanidine and dimethylamine, highlighting a profile related to oxidative damage, and to tyrosine and glutamine, related to a decreased breakdown of aromatic aminoacids and ammonia detoxification, respectively. 1-methylnicotinamide, a catabolic intermediate of nicotinamide-adenine-dinucleotide, was significantly increased in HCV-patients and restored after HCV-clearance, probably due to the reduced hepatic inflammation. 3-hydroxy-3-methylbutyrate, an intermediate of leucine-catabolism which was permanently restored after HCV-clearance, suggested an improvement of skeletal muscle protein synthesis. Finally, 3-hydroxyisobutyrate and 2,3-dihydroxy-2-methylbutyrate, intermediates of valine-catabolism, glycine and choline increased temporarily during therapy, resulting as potential biomarkers of DAAs systemic effects.
2021
NMR-based metabolomics; hepatitis C virus (HCV); direct-acting antivirals (DAAs); oxidative stress; amino acid metabolism
01 Pubblicazione su rivista::01a Articolo in rivista
Urinary metabolomics of HCV patients with severe liver fibrosis before and during the sustained virologic response achieved by direct acting antiviral treatment / Biliotti, Elisa; Giampaoli, Ottavia; Sciubba, Fabio; Marini, Federico; Tomassini, Alberta; Palazzo, Donatella; Capuani, Giorgio; Esvan, Rozenn; Spaziante, Martina; Taliani, Gloria; Miccheli, Alfredo. - In: BIOMÉDECINE & PHARMACOTHÉRAPIE. - ISSN 0753-3322. - 143:(2021), pp. 1-12. [10.1016/j.biopha.2021.112217]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1570609
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