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Proteomic characterization of hepatitis C eradication: enzyme switch in the healing liver

Babudieri, Sergio and Soddu, Andrea and Nieddu, Paolo and Tanca, Alessandro and Madeddu, Giordano and Addis, Maria Filippa and Pagnozzi, Daniela and Cossu Rocca, Paolo Alessandro and Massarelli, Giovannino and Dore, Maria Pina and Uzzau, Sergio and Mura, Maria Stella Anna (2013) Proteomic characterization of hepatitis C eradication: enzyme switch in the healing liver. Journal of clinical virology, Vol. 57 (3), p. 274-278. eISSN 1873-5967. Article.

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DOI: 10.1016/j.jcv.2013.03.002

Abstract

Lipid pathway impairment, decrease in the antioxidant pool and downregulation in amino-acid metabolism are just some of the metabolic variations attributed to chronic HCV infection. All of them have been studied separately, mainly in animal models.
Thanks to proteomic analysis we managed to describe (for the fist time to the best of our knowledge), in vivo and in humans, the metabolic alterations caused by HCV, and the recovery of the same alterations during HCV treatment.
We performed proteomic analysis on liver specimens of a 28-year-old woman affected by hepatitis C genotype 1a, alcoholism and diabetes mellitus type 1, before and after antiviral treatment with pegylated interferon alpha 2b and ribavirin. The subject, thanks to a patient-tailored therapy, reached Sustained Virological Response. Throughout the treatment period the patient was monitored with subsequent biochemical, clinical and psychological examinations.
The data obtained by the patient's close monitoring suggest a direct interaction between insulin resistance and an active HCV genotype 1 infection, with a leading role played by the infection, and not by insulin resistance, as demonstrated by the sharp fall of the insulin units needed per day during treatment.
The proteomic analysis showed that after therapy, a downregulation of enzymes involved in amino acid metabolism, glycolysis/gluconeogenesis and alcohol catabolism takes place, the latter probably due to cessation of alcohol abuse. On the contrary, the metabolic pathways linked to metabolism of the reactive oxygen species were upregulated after therapy. Finally, a significant alteration in the pathway regulated by peroxisome proliferator-activated receptor alpha (PPARA), a major regulator of lipid metabolism in the liver, was reported.
These “real time” data confirm in vivo, in humans, that during HCV infection, the pathways related to fatty acids, glucose metabolism and free radical scavenging are inhibited. The same enzyme deficit is completely recovered after HCV eradication.

Item Type:Article
ID Code:8912
Status:Published
Refereed:Yes
Uncontrolled Keywords:Antiviral therapy, FFPE, genotype 1, HCV, insulin resistance, metabolism proteomics
Subjects:Area 06 - Scienze mediche > MED/17 Malattie infettive
Area 06 - Scienze mediche > MED/12 Gastroenterologia
Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Area 06 - Scienze mediche > MED/08 Anatomia patologica
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > Porto Conte Ricerche, Alghero
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Medicina Clinica e Sperimentale
Publisher:Elsevier
eISSN:1873-5967
Deposited On:23 Apr 2013 13:30

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