Open AccessHepatitis C virus intrinsic molecular determinants may contribute to the development of cholestatic hepatitis after liver transplantation
Author(s) -
Martina Gambato,
Josep Gregori,
Josep Quer,
George Koutsoudakis,
Patricia González,
Noelia Caro-Pérez,
Damir García-Cehic,
Neris García-González,
Fernando GonzálezCandelas,
Juan Ignacio Esteban,
Gonzalo Crespo,
Miquel Navasa,
Xavier Forns,
Sofía PérezdelPulgar
Publication year - 2019
Publication title -
journal of general virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.55
H-Index - 167
eISSN - 1465-2099
pISSN - 0022-1317
DOI - 10.1099/jgv.0.001175
Subject(s) - viral quasispecies , biology , hepatitis c virus , virology , liver transplantation , ns5b , hepacivirus , hepatitis c , transplantation , virus , hepatitis , immunology , medicine
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 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.