Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2023; 15(11): 1237-1249
Published online Nov 27, 2023. doi: 10.4254/wjh.v15.i11.1237
Metabolomics in chronic hepatitis C: Decoding fibrosis grading and underlying pathways
Adriana Camargo Ferrasi, Samara Vitória Granja Lima, Aline Faria Galvani, Jeany Delafiori, Flavia Luísa Dias-Audibert, Rodrigo Ramos Catharino, Giovanni Faria Silva, Roberta Rodrigues Praxedes, Driele Bretones Santos, Dayane Trevisan de Macedo Almeida, Estela Oliveira Lima
Adriana Camargo Ferrasi, Samara Vitória Granja Lima, Aline Faria Galvani, Giovanni Faria Silva, Roberta Rodrigues Praxedes, Driele Bretones Santos, Dayane Trevisan de Macedo Almeida, Estela Oliveira Lima, Department of Internal Medicine, Sao Paulo State University, Botucatu 18618-686, Brazil
Jeany Delafiori, Flavia Luísa Dias-Audibert, Rodrigo Ramos Catharino, Innovare Biomarkers Laboratory, University of Campinas, Campinas 13083-877, Brazil
Author contributions: Ferrasi AC, Lima EO, Delafiori J and Dias-Audibert FL performed mass spectrometry experiments; Ferrasi AC, Galvani AF, Santos DB, Silva GF, and Praxedes RR performed biofluid collection and selection and provided clinical support; Ferrasi AC, Almeida DTM, Lima EO, Praxedes RR, and Lima SVG analyzed the data and prepared the Figures; Ferrasi AC and Lima SVG wrote the manuscript; Lima EO, Silva GF, and Catharino RR revised the manuscript; Catharino RR provided the infrastructure and methodological support; Ferrasi AC and Lima EO designed, managed, and supervised the study; All authors approved the final version of the article.
Supported by São Paulo Research Foundation, No. 2021/04753-0.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at the Botucatu Medical School.
Informed consent statement: All the participants in this study signed the Informed Consent Form.
Conflict-of-interest statement: The authors declare that there is no conflict-of-interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Adriana Camargo Ferrasi, PhD, Professor, Department of Internal Medicine, Sao Paulo State University, s/n, Professor Armando Alves Avenue, Unesp, Botucatu 18618-686, Brazil. adriana.ferrasi@unesp.br
Received: August 22, 2023
Peer-review started: August 22, 2023
First decision: September 6, 2023
Revised: September 22, 2023
Accepted: October 23, 2023
Article in press: October 23, 2023
Published online: November 27, 2023
Processing time: 94 Days and 5.8 Hours
ARTICLE HIGHLIGHTS
Research background

Chronic hepatitis C (CHC) is an infectious disease caused by the hepatitis C virus, leading to liver issues like fibrosis, cirrhosis, cancer, and death. The accurate fibrosis stage identification is crucial for treatment decisions and predicting outcomes. Thus, blood markers are a source of relevant information on the staging of fibrosis, in a less invasive and representative way, compared to percutaneous biopsies.

Research motivation

Currently, approaches to staging fibrosis are invasive, subject to sampling errors and subjectivity between observers. In clinical routine, blood markers should be considered a relevant source of information. However, current approaches are limited to routine biochemical tests associated with clinical information, which is not very informative. Analyses based on liquid biopsy are less invasive, and blood plasma, since it circulates throughout the body, can provide information on pathologies that have not yet manifested themselves clinically, positively impacting on prognosis.

Research objectives

Analyze the plasmatic metabolome of CHC patients, looking for potential biomarkers to stratify these lesions.

Research methods

Plasma metabolites from hepatitis C patients and 50 healthy volunteer participants were analyzed using the LTQ Mass Spectrometer. The sample and the control group were classified into Fibrosis grades was classified using the Metavir score. Liver samples were collected by percutaneous biopsy before any treatment and then analyzed histologically. The most relevant metabolites were categorized using the METLIN online metabolomics database. The molecules of interest were added to a list of candidates and subsequently fragmented in silico using the MassFrontier tool. Molecules compatible with those generated experimentally were then selected for functional analysis.

Research results

For each degree of fibrosis, six differential metabolites were identified that were able to establish an interesting grouping trend among patients with the same degree of fibrosis.

Research conclusions

The results of this study suggest that liquid biopsy analyzes of plasma metabolites are a good source of molecular biomarkers capable of stratifying patients with CHC according to their fibrosis grade.

Research perspectives

Some of the observed biomarkers, once validated, have the potential for application as prognostic biomarkers. This study has innovative potential regarding the detection of pre-clinical biomarkers in easily accessible plasma using minimally invasive methods.