6533b825fe1ef96bd1281dd7

RESEARCH PRODUCT

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

Miquel NavasaXavier FornsJosep QuerJuan Ignacio EstebanP. GonzálezM. GambatoJosep GregoriGeorge KoutsoudakisFernando González-candelasDamir Garcia-cehicSofía Pérez-del-pulgarNeris García-gonzálezGonzalo CrespoNoelia Caro-pérezNoelia Caro-pérez

subject

0301 basic medicineMalemedicine.medical_specialtyGenotypeDeep sequencingSequence analysismedicine.medical_treatmentHepatitis C virus030106 microbiologyViral quasispeciesHepacivirusLiver transplantationBiologyViral Nonstructural ProteinsGraft lossmedicine.disease_causeGastroenterology03 medical and health scienceschemistry.chemical_compoundVirologyInternal medicinemedicineHumansNS5BAgedLiver transplantationHepatitis C virusHigh-Throughput Nucleotide SequencingHepatitis CHepatitis C ChronicMiddle Agedmedicine.diseaseVirologyCholestatic hepatitis CLiver TransplantationJaundice ObstructiveQuasispecies030104 developmental biologychemistryCholestatic hepatitisFemale

description

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.

yearjournalcountryeditionlanguage
2018-11-20
10.1099/jgv.0.001175https://ddd.uab.cat/record/223341