Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies

Viral diversity and disease progression in chronic infections, and particularly how quasispecies structure affects antiviral treatment, remain key unresolved issues. Previous studies show that advanced liver fibrosis in long-term viral infections is linked to higher rates of antiviral treatment fail...

Full description

Saved in:
Bibliographic Details
Main Authors: Josep Gregori, Marta Ibañez-Lligoña, Sergi Colomer-Castell, Carolina Campos, Damir García-Cehic, Josep Quer
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/12/11/2213
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850226712400363520
author Josep Gregori
Marta Ibañez-Lligoña
Sergi Colomer-Castell
Carolina Campos
Damir García-Cehic
Josep Quer
author_facet Josep Gregori
Marta Ibañez-Lligoña
Sergi Colomer-Castell
Carolina Campos
Damir García-Cehic
Josep Quer
author_sort Josep Gregori
collection DOAJ
description Viral diversity and disease progression in chronic infections, and particularly how quasispecies structure affects antiviral treatment, remain key unresolved issues. Previous studies show that advanced liver fibrosis in long-term viral infections is linked to higher rates of antiviral treatment failures. Additionally, treatment failure is associated with high quasispecies fitness, which indicates greater viral diversity and adaptability. As a result, resistant variants may emerge, reducing retreatment effectiveness and increasing the chances of viral relapse. Additionally, using a mutagenic agent in monotherapy can accelerate virus evolution towards a flat-like quasispecies structure. This study examines 19 chronic HCV patients who failed direct-acting antiviral (DAA) treatments, using NGS to analyze quasispecies structure in relation to fibrosis as a marker of infection duration. Results show that HCV evolves towards a flat-like quasispecies structure over time, leading also to advanced liver damage (fibrosis F3 and F4/cirrhosis). Based on our findings and previous research, we propose that the flat-like fitness quasispecies structure is the final stage of any quasispecies in chronic infections unless eradicated. The longer the infection persists, the lower the chances of achieving a cure. Interestingly, this finding may also be applicable to other chronic infection and drug resistance in cancer.
format Article
id doaj-art-de900dd929b04ca6ac072504e2534cd5
institution OA Journals
issn 2076-2607
language English
publishDate 2024-10-01
publisher MDPI AG
record_format Article
series Microorganisms
spelling doaj-art-de900dd929b04ca6ac072504e2534cd52025-08-20T02:04:59ZengMDPI AGMicroorganisms2076-26072024-10-011211221310.3390/microorganisms12112213Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a QuasispeciesJosep Gregori0Marta Ibañez-Lligoña1Sergi Colomer-Castell2Carolina Campos3Damir García-Cehic4Josep Quer5Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut of Research (VHIR), Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, SpainLiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut of Research (VHIR), Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, SpainLiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut of Research (VHIR), Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, SpainLiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut of Research (VHIR), Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, SpainDepartment of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USALiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut of Research (VHIR), Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, SpainViral diversity and disease progression in chronic infections, and particularly how quasispecies structure affects antiviral treatment, remain key unresolved issues. Previous studies show that advanced liver fibrosis in long-term viral infections is linked to higher rates of antiviral treatment failures. Additionally, treatment failure is associated with high quasispecies fitness, which indicates greater viral diversity and adaptability. As a result, resistant variants may emerge, reducing retreatment effectiveness and increasing the chances of viral relapse. Additionally, using a mutagenic agent in monotherapy can accelerate virus evolution towards a flat-like quasispecies structure. This study examines 19 chronic HCV patients who failed direct-acting antiviral (DAA) treatments, using NGS to analyze quasispecies structure in relation to fibrosis as a marker of infection duration. Results show that HCV evolves towards a flat-like quasispecies structure over time, leading also to advanced liver damage (fibrosis F3 and F4/cirrhosis). Based on our findings and previous research, we propose that the flat-like fitness quasispecies structure is the final stage of any quasispecies in chronic infections unless eradicated. The longer the infection persists, the lower the chances of achieving a cure. Interestingly, this finding may also be applicable to other chronic infection and drug resistance in cancer.https://www.mdpi.com/2076-2607/12/11/2213quasispecies diversityquasispecies maturityquasispecies fitnessfibrosisliver damageantiviral treatment failure
spellingShingle Josep Gregori
Marta Ibañez-Lligoña
Sergi Colomer-Castell
Carolina Campos
Damir García-Cehic
Josep Quer
Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies
Microorganisms
quasispecies diversity
quasispecies maturity
quasispecies fitness
fibrosis
liver damage
antiviral treatment failure
title Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies
title_full Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies
title_fullStr Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies
title_full_unstemmed Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies
title_short Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies
title_sort association of liver damage and quasispecies maturity in chronic hcv patients the fate of a quasispecies
topic quasispecies diversity
quasispecies maturity
quasispecies fitness
fibrosis
liver damage
antiviral treatment failure
url https://www.mdpi.com/2076-2607/12/11/2213
work_keys_str_mv AT josepgregori associationofliverdamageandquasispeciesmaturityinchronichcvpatientsthefateofaquasispecies
AT martaibanezlligona associationofliverdamageandquasispeciesmaturityinchronichcvpatientsthefateofaquasispecies
AT sergicolomercastell associationofliverdamageandquasispeciesmaturityinchronichcvpatientsthefateofaquasispecies
AT carolinacampos associationofliverdamageandquasispeciesmaturityinchronichcvpatientsthefateofaquasispecies
AT damirgarciacehic associationofliverdamageandquasispeciesmaturityinchronichcvpatientsthefateofaquasispecies
AT josepquer associationofliverdamageandquasispeciesmaturityinchronichcvpatientsthefateofaquasispecies