Hepatitis C virus intrinsic molecular determinants may contribute to the development of cholestatic hepatitis after liver transplantation

Cholestatic hepatitis C (CHC) is a severe form of hepatitis C virus (HCV) infection recurrence that leads to high graft loss rates early after liver transplantation (LT). To investigate the pathogenic mechanisms of CHC, we analysed HCV quasispecies in CHC patients compared to a control group (mild h...

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Detalles Bibliográficos
Autores: Gambato, Martina, Gregori i Font, Josep|||0000-0002-4253-8015, Quer, Josep|||0000-0003-0014-084X, Koutsoudakis, George, González, Patricia, Caro-Pérez, Noelia, Garcia-Cehic, D.|||0000-0002-0009-038X, García-González, Neris, González-Candelas, Fernando|||0000-0002-0879-5798, Ignacio Esteban, Juan, Crespo, Gonzalo|||0000-0002-1178-4897, Navasa, Miquel|||0000-0002-3130-9604, Forns, Xavier|||0000-0002-8188-1764, Pérez-Del-Pulgar, Sofía
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:223341
Acceso en línea:https://ddd.uab.cat/record/223341
https://dx.doi.org/urn:doi:10.1099/jgv.0.001175
Access Level:acceso abierto
Palabra clave:Hepatitis C virus
Liver transplantation
Cholestatic hepatitis C
Quasispecies
Deep sequencing
Descripción
Sumario:Cholestatic hepatitis C (CHC) is a severe form of hepatitis C virus (HCV) infection recurrence that leads to high graft loss rates early after liver transplantation (LT). To investigate the pathogenic mechanisms of CHC, we analysed HCV quasispecies in CHC patients compared to a control group (mild hepatitis C recurrence) by deep pyrosequencing. At the time of LT, NS5B quasispecies complexity was similar between the two groups but, after LT, it decreased more sharply in CHC patients than in the control group. Interestingly, the major variant before LT propagated efficiently and remained as the dominant sequence after LT in 62% of CHC patients versus 11% of controls (P=0.031). Sequence analysis of the complete nonstructural region in a limited number of patients revealed a potential 12 aa signature specific to the CHC group. These data suggest that intrinsic molecular determinants in the circulating HCV quasispecies may provide a fitness advantage, contributing to the development of CHC.

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