Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients

Cirrhosis derived from chronic hepatitis C virus (HCV) infection is still a common indication for liver transplantation (LT). Reinfection of the engrafted liver is universal in patients with detectable viral RNA at the time of transplant and causes fast progression of cirrhosis (within 5 years) in a...

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Autores principales:	Meritxell Llorens-Revull, Josep Gregori, Cristina Dopazo, Francisco Rodriguez-Frías, Damir Garcia-Cehic, Maria Eugenia Soria, Qian Chen, Ariadna Rando, Celia Perales, Juan Ignacio Esteban, Josep Quer, Itxarone Bilbao
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hepatitis C virus liver transplantation fibrosis variability complexity measures viral load Genetics QH426-470
Acceso en línea:	https://doaj.org/article/863aab83ea9e4a9488ac9990d0ff18db
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spelling	oai:doaj.org-article:863aab83ea9e4a9488ac9990d0ff18db2021-11-25T17:41:20ZStudy of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients10.3390/genes121117312073-4425https://doaj.org/article/863aab83ea9e4a9488ac9990d0ff18db2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1731https://doaj.org/toc/2073-4425Cirrhosis derived from chronic hepatitis C virus (HCV) infection is still a common indication for liver transplantation (LT). Reinfection of the engrafted liver is universal in patients with detectable viral RNA at the time of transplant and causes fast progression of cirrhosis (within 5 years) in around one-third of these patients. To prevent damage to the liver graft, effective direct-acting antiviral (DAA) therapy is required as soon as possible. However, because of post-LT clinical instability, it is difficult to determine the optimal time to start DAAs with a low risk of complications. Evaluate changes in quasispecies complexity following LT and seek a predictive index of fast liver damage progression to determine the timing of DAA initiation. HCV genomes isolated from pre-LT and 15-day post-LT serum samples of ten patients, who underwent orthotopic LT, were quantified and sequenced using a next-generation sequencing platform. Sequence alignments, phylogenetic trees, quasispecies complexity measures, biostatistics analyses, adjusted R2 values, and analysis of variance (ANOVA) were carried out. Three different patterns of reinfection were observed (viral bottlenecking, conserved pre-LT population, and mixed populations), suggesting that bottlenecking or homogenization of the viral population is not a generalized effect after liver graft reinfection. None of the quasispecies complexity measures predicted the future degree of liver damage. Higher and more uniform viral load (VL) values were observed in all pre-LT samples, but values were more dispersed in post-LT samples. However, VL increased significantly from the pre-LT to 15-day post-LT samples in patients with advanced fibrosis at 1-year post-LT, suggesting that a VL increase on day 15 may be a predictor of fast liver fibrosis progression. HCV kinetics after LT differ between patients and are not fibrosis-dependent. Higher VL at day 15 post-LT versus pre-LT samples may predict fast liver fibrosis progression.Meritxell Llorens-RevullJosep GregoriCristina DopazoFrancisco Rodriguez-FríasDamir Garcia-CehicMaria Eugenia SoriaQian ChenAriadna RandoCelia PeralesJuan Ignacio EstebanJosep QuerItxarone BilbaoMDPI AGarticlehepatitis C virusliver transplantationfibrosisvariabilitycomplexity measuresviral loadGeneticsQH426-470ENGenes, Vol 12, Iss 1731, p 1731 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatitis C virus liver transplantation fibrosis variability complexity measures viral load Genetics QH426-470
spellingShingle	hepatitis C virus liver transplantation fibrosis variability complexity measures viral load Genetics QH426-470 Meritxell Llorens-Revull Josep Gregori Cristina Dopazo Francisco Rodriguez-Frías Damir Garcia-Cehic Maria Eugenia Soria Qian Chen Ariadna Rando Celia Perales Juan Ignacio Esteban Josep Quer Itxarone Bilbao Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients
description	Cirrhosis derived from chronic hepatitis C virus (HCV) infection is still a common indication for liver transplantation (LT). Reinfection of the engrafted liver is universal in patients with detectable viral RNA at the time of transplant and causes fast progression of cirrhosis (within 5 years) in around one-third of these patients. To prevent damage to the liver graft, effective direct-acting antiviral (DAA) therapy is required as soon as possible. However, because of post-LT clinical instability, it is difficult to determine the optimal time to start DAAs with a low risk of complications. Evaluate changes in quasispecies complexity following LT and seek a predictive index of fast liver damage progression to determine the timing of DAA initiation. HCV genomes isolated from pre-LT and 15-day post-LT serum samples of ten patients, who underwent orthotopic LT, were quantified and sequenced using a next-generation sequencing platform. Sequence alignments, phylogenetic trees, quasispecies complexity measures, biostatistics analyses, adjusted R2 values, and analysis of variance (ANOVA) were carried out. Three different patterns of reinfection were observed (viral bottlenecking, conserved pre-LT population, and mixed populations), suggesting that bottlenecking or homogenization of the viral population is not a generalized effect after liver graft reinfection. None of the quasispecies complexity measures predicted the future degree of liver damage. Higher and more uniform viral load (VL) values were observed in all pre-LT samples, but values were more dispersed in post-LT samples. However, VL increased significantly from the pre-LT to 15-day post-LT samples in patients with advanced fibrosis at 1-year post-LT, suggesting that a VL increase on day 15 may be a predictor of fast liver fibrosis progression. HCV kinetics after LT differ between patients and are not fibrosis-dependent. Higher VL at day 15 post-LT versus pre-LT samples may predict fast liver fibrosis progression.
format	article
author	Meritxell Llorens-Revull Josep Gregori Cristina Dopazo Francisco Rodriguez-Frías Damir Garcia-Cehic Maria Eugenia Soria Qian Chen Ariadna Rando Celia Perales Juan Ignacio Esteban Josep Quer Itxarone Bilbao
author_facet	Meritxell Llorens-Revull Josep Gregori Cristina Dopazo Francisco Rodriguez-Frías Damir Garcia-Cehic Maria Eugenia Soria Qian Chen Ariadna Rando Celia Perales Juan Ignacio Esteban Josep Quer Itxarone Bilbao
author_sort	Meritxell Llorens-Revull
title	Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients
title_short	Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients
title_full	Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients
title_fullStr	Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients
title_full_unstemmed	Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients
title_sort	study of quasispecies complexity and liver damage progression after liver transplantation in hepatitis c virus infected patients
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/863aab83ea9e4a9488ac9990d0ff18db
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Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients

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