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
Abstract
BACKGROUND

Chronic Hepatitis C (CHC) affects 71 million people globally and leads to liver issues such as fibrosis, cirrhosis, cancer, and death. A better understanding and prognosis of liver involvement are vital to reduce morbidity and mortality. The accurate identification of the fibrosis stage is crucial for making treatment decisions and predicting outcomes. Tests used to grade fibrosis include histological analysis and imaging but have limitations. Blood markers such as molecular biomarkers can offer valuable insights into fibrosis.

AIM

To identify potential biomarkers that might stratify these lesions and add information about the molecular mechanisms involved in the disease.

METHODS

Plasma samples were collected from 46 patients with hepatitis C and classified into fibrosis grades F1 (n = 13), F2 (n = 12), F3 (n = 6), and F4 (n = 15). To ensure that the identified biomarkers were exclusive to liver lesions (CHC fibrosis), healthy volunteer participants (n = 50) were also included. An untargeted metabolomic technique was used to analyze the plasma metabolites using mass spectrometry and database verification. Statistical analyses were performed to identify differential biomarkers among groups.

RESULTS

Six differential metabolites were identified in each grade of fibrosis. This six-metabolite profile was able to establish a clustering tendency in patients with the same grade of fibrosis; thus, they showed greater efficiency in discriminating grades.

CONCLUSION

This study suggests that some of the observed biomarkers, once validated, have the potential to be applied as prognostic biomarkers. Furthermore, it suggests that liquid biopsy analyses of plasma metabolites are a good source of molecular biomarkers capable of stratifying patients with CHC according to fibrosis grade.

Keywords: Chronic Hepatitis C, Fibrosis, Metabolome, Biomarkers, Plasma, Liquid biopsy

Core Tip: Chronic Hepatitis C affects 71 million people globally and leads to liver fibrosis, cirrhosis, cancer, and death. The accurate staging of fibrosis is crucial for treatment decisions and outcome prediction. Blood markers are a relevant source of information, and various molecular biomarkers have been investigated to characterize liver fibrosis. We analyzed plasma metabolites by mass spectrometry in 50 healthy participants, and in 46 patients with hepatitis C and classified them into fibrosis grades F1-F4. Six differential metabolites were identified in each grade of fibrosis; their biochemical pathways were analyzed and suggests molecular mechanisms involved in the disease.