4b2cfb7e1e97d117a8d7a36f69cb6e50 pmc_34828337.pdf 59880a2a304ab97a3ed4d679d129e9bef5e80ab9 pmc_34828337.pdf 7a1d9cbbb03ab4d0eb30b1de0722b0004292bcd47ba74138dc65a7df9a5c90d9 pmc_34828337.pdf Title: Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients Subject: 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.8pt Keywords: hepatitis C virus; liver transplantation; fibrosis; variability; complexity measures; viral load 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 and Itxarone Bilbao Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Nov 22 09:26:36 2021 CET ModDate: Mon Nov 22 09:32:44 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2363470 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SXQPWE+VnURWPalladioL Type 1 Custom yes yes no 10 0 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(Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:38:07 CEST RepresentationInformation: pmc_34828337.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:06:20 CEST Size: 2363470 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 401 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: RNA Extraction, RT-PCR, Heminested-PCR Amplification and Quantification Destination: subsection.2.1 Item: Title: Ultradeep Pyrosequencing (UDPS) Destination: subsection.2.2 Item: Title: Nucleotide Haplotypes and Diversity Analyses Destination: subsection.2.3 Item: Title: Phylogenetic Analysis Destination: subsection.2.4 Item: Title: Biostatistic Analyses Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Viral Kinetics and Histological Grade Destination: subsection.3.1 Item: Title: Phylogenetic Studies Destination: subsection.3.2 Item: Title: Unidimensional Analyses Destination: subsection.3.3 Item: Title: Principal Components Analysis Destination: subsection.3.4 Item: Title: Associations between Diversity Measures and Fibrosis at 1 Year Post-LT Destination: subsection.3.5 Item: Title: Associations between VL and Fibrosis at 1 Year Post-LT Destination: subsection.3.6 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients 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 and Itxarone Bilbao Subject: 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.8pt Keywords: hepatitis C virus; liver transplantation; fibrosis; variability; complexity measures; viral load Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Nov 22 09:26:36 CET 2021 ModDate: Mon Nov 22 09:32:44 CET 2021 ID: 0xfe538872fbc5fa0dc0225a6b636cccc1, 0xfe538872fbc5fa0dc0225a6b636cccc1 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: AYVCVS+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 122 FontDescriptor: FontName: AYVCVS+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: DKZMYW+CMSY10 FontSubset: true FirstChar: 2 LastChar: 48 FontDescriptor: FontName: DKZMYW+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: KBLIOM+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: 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