Hepatitis C virus intrinsic molecular determinants may contribute to the development of cholestatic hepatitis after liver transplantation
Por:
Gambato M, Gregori J, Quer J, Koutsoudakis G, González P, Caro-Pérez N, García-Cehic D, García-González N, González-Candelas F, Esteban JI, Crespo G, Navasa M, Forns X and Pérez-Del-Pulgar S
Publicada:
1 ene 2019
Ahead of Print:
19 nov 2018
Categoría:
Virology
Resumen:
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 non-structural region in a limited number of patients revealed a potential 12 as 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.
Filiaciones:
Gambato M:
†?Present address: Multivisceral Transplant Unit and Gastroenterology, Padova University Hospital, Padova, Italy
2?Multivisceral Transplant Unit and Gastroenterology, Padova University Hospital, Padova, Italy
1?Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
Gregori J:
4?Roche Diagnostics SL. Sant Cugat del Vallès, Barcelona, Spain
3?Liver Unit, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron, CIBERehd, Barcelona, Spain
Quer J:
3?Liver Unit, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron, CIBERehd, Barcelona, Spain
Koutsoudakis G:
1?Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
González P:
1?Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
Caro-Pérez N:
‡?Present address: Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden
1?Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
García-Cehic D:
3?Liver Unit, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron, CIBERehd, Barcelona, Spain
:
5?Joint Research Unit Infección y Salud Pública, FISABIO-Universitat de València, I2SysBio, CIBERESP, Valencia, Spain
:
5?Joint Research Unit Infección y Salud Pública, FISABIO-Universitat de València, I2SysBio, CIBERESP, Valencia, Spain
Esteban JI:
3?Liver Unit, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron, CIBERehd, Barcelona, Spain
Crespo G:
1?Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
Navasa M:
1?Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
Forns X:
1?Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
Pérez-Del-Pulgar S:
1?Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
Green Submitted, Bronze
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