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

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

Biomedicine & Pharmacotherapy (Nov 2021)

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

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

Affiliations

Elisa Biliotti: Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
Ottavia Giampaoli: Department of Chemistry, Sapienza University of Rome, Rome, Italy; NMR-based Metabolomics Laboratory (NMLab), Sapienza University of Rome, Rome, Italy
Fabio Sciubba: Department of Chemistry, Sapienza University of Rome, Rome, Italy; NMR-based Metabolomics Laboratory (NMLab), Sapienza University of Rome, Rome, Italy
Federico Marini: Department of Chemistry, Sapienza University of Rome, Rome, Italy; NMR-based Metabolomics Laboratory (NMLab), Sapienza University of Rome, Rome, Italy
Alberta Tomassini: Department of Chemistry, Sapienza University of Rome, Rome, Italy; NMR-based Metabolomics Laboratory (NMLab), Sapienza University of Rome, Rome, Italy
Donatella Palazzo: Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
Giorgio Capuani: Department of Chemistry, Sapienza University of Rome, Rome, Italy; NMR-based Metabolomics Laboratory (NMLab), Sapienza University of Rome, Rome, Italy
Rozenn Esvan: Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
Martina Spaziante: Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
Gloria Taliani: Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
Alfredo Miccheli: NMR-based Metabolomics Laboratory (NMLab), Sapienza University of Rome, Rome, Italy; Department of Environmental Biology, Sapienza University of Rome, Rome, Italy; Correspondence to: Department of Environmental Biology, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.

Journal volume & issue: Vol. 143
p. 112217

Abstract

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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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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