Baseline Amino Acid Substitutions in the NS5A ISDR and PKR Binding Domain of Hepatitis C and Different Fibrosis Levels and Levels of Development of Hepatocellular Carcinoma in Patients Treated with DAAs.
Aged
Carcinoma, Hepatocellular
/ etiology
Computational Biology
/ methods
Female
Hepacivirus
/ physiology
Hepatitis C, Chronic
/ complications
Host-Pathogen Interactions
Humans
Liver Cirrhosis
/ diagnosis
Liver Neoplasms
/ etiology
Male
Middle Aged
Protein Binding
Protein Interaction Domains and Motifs
RNA, Viral
Viral Nonstructural Proteins
/ chemistry
DAA/direct-acting antivirals
HCV
ISDR and PKR-bd
fibrosis levels
hepatocellular carcinoma
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
25 02 2020
25 02 2020
Historique:
received:
24
01
2020
revised:
17
02
2020
accepted:
22
02
2020
entrez:
29
2
2020
pubmed:
29
2
2020
medline:
23
2
2021
Statut:
epublish
Résumé
Variations in the interferon sensitivity-determining region (ISDR) within the NS5A region were related to the development of hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV). The aim of the study was to investigate a relationship between ISDR/PKR substitutions and their association with liver fibrosis or HCC development. A total of 316 patients infected with HCV and treated with DAAs were evaluated. HCV RNA was quantified and sequenced before treatment. The liver fibrosis stage was assessed by transient elastography and equalized to METAVIR scores. Multivariate analysis showed that ≥3 substitutions in ISDR and ≥6 in PKR-bd were significantly associated with advanced fibrosis. Advanced fibrosis was observed in patients with higher substitutions in ISDR and PKR-bd. A higher correlation between advanced fibrosis and a high frequency of ≥3 substitutions in ISDR and ≥6 in PKR-bd was observed in patients infected with genotype 2c. In addition, in a higher proportion of HCC patients, advanced fibrosis (40.4% vs. 88.2%;
Identifiants
pubmed: 32106574
pii: v12030255
doi: 10.3390/v12030255
pmc: PMC7150791
pii:
doi:
Substances chimiques
RNA, Viral
0
Viral Nonstructural Proteins
0
NS-5 protein, hepatitis C virus
EC 2.7.7.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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