scholarly journals Association of Interferon Regulatory Factor-3 Gene Polymorphisms With Infection and Antiviral Efficacy of Chronic Hepatitis C Virus

Author(s):  
Xun-Jun Yang ◽  
Xiao-Ou Wang ◽  
Linna Liu ◽  
Yao Chen ◽  
Song-Dao Ye

Abstract Background Hepatitis C virus (HCV) is a major public health concern in developing countries. Pathogenesis of hepatitis C infection is poorly understood. Previously, we found higher Interferon Regulatory Factor-3 (IRF-3) expression in HCV-infected patients. However, the effect of IRF-3 polymorphism on the incidence of HCV infection and antiviral efficacy has not been sufficiently evaluated.Methods We retrospectively enrolled 178 patients with chronic hepatitis C (CHC) and 82 matched healthy controls between 2016 and 2019 at the Second Hospital of Wenzhou Medical University, China. All patients received a standard dose of polyethylene glycol interferon + ribavirin (PR regimen), and were divided into the response, non-response, sustained virological response (SVR), and non-sustained virological response (NSVR) groups based on their HCV RNA levels. Gene polymorphisms were detected by DNA sequencing, and the plasma IRF-3 and IFN-β levels were measured by ELISA to assess the impact of IRF-3 gene variations and contents on the risk of HCV infection and antiviral efficacy.Results Plasma contents of IRF-3 and IFN-β were significantly different between the CHC and control groups, the response and non-response groups, and the SVR and non-SVR groups (p<0.05). rs2304206 C>T but not rs2304204A>G was associated with increased risk for CHC (OR= 2.35 (95% CI: 1.30 to 4.24), p = 0.004), and reduced antiviral efficacy between both response groups (OR= 1.86 (95% CI: 1.06 to 3.24), p = 0.028) and SVR groups (OR= 1.79 (95% CI:1.05 to 3.06), p = 0.030). Haplotype GT type suffered negative consequence between the CHC and control groups, the responder and non-responder groups, and the SVR and non-SVR groups (p=0.004, 0.028, 0.030). The content of IFR-3 in CT genotype of rs2304206 was higher than that in CC genotype.Conclusion The polymorphism of IFR-3 affects the plasma levels of IFR-3 and associated with HCV infection and interferon antiviral efficacy, where the T allele of rs2304206 may be a susceptibility factor for CHC and adversely impact interferon antiviral response.

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 831
Author(s):  
Oscar C. Araujo ◽  
Vanessa S. de Paula ◽  
Kycia M. do Ó ◽  
Cristiane A. Villela-Nogueira ◽  
Natalia M. Araujo

Oxidative stress contributes to hepatitis C virus (HCV)–induced liver damage. Host genetic factors may be involved in progression of HCV infection. The present study was conducted to determine the influence of glutathione S-transferase (GST)-M1 and T1 gene polymorphisms during different stages of HCV infection, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The study population comprised 190 patients (47 with chronic hepatitis, 83 with cirrhosis (without HCC), and 60 with HCC). GSTM1 and GSTT1 gene polymorphisms were analyzed via multiplex polymerase chain reaction. The GSTT1-null genotype was more commonly detected in patients with cirrhosis (n = 17; 20.5%) and HCC (n = 13; 21.7%) than those with chronic hepatitis (n = 3; 6.4%). The differences in GSTT1-null genotype frequencies were significant for cirrhosis vs. chronic hepatitis (odds ratio, OR, 3.778 (95% confidence interval, CI, 1.045–13.659); p = 0.043) and HCC vs. chronic hepatitis (OR, 4.057 (95% CI, 1.083–15.201); p = 0.038) groups. However, the incidence of individual GSTM1-null or combined GSTM1/GSTT1 double-null genotypes did not vary significantly between the groups. Our collective findings support the utility of the GSTT1-null genotype as a useful biomarker for liver disease progression in Brazilian patients with chronic hepatitis C.


2011 ◽  
Vol 152 (22) ◽  
pp. 876-881
Author(s):  
Alajos Pár

The review discusses the genetic polymorphisms involved in the pathogenesis of hepatitis C virus (HCV) infection, that may determine the outcome of disease. In this field earlier both certain major histocompatibility complex (MHC) alleles and some cytokine gene variants have also been studied. Recently, the genome-wide association study (GWAS) and targeted single nucleotide polymorphism (SNP) analysis have revealed that a variant in the promoter region of interleukin-28B (IL-28B) gene is strongly linked to viral clearance and it may be the strongest pretreatment predictor of treatment response in chronic hepatitis C. Last year it was shown that two genetic variants leading to inosine triphosphatase deficiency protect against haemolytic anemia in patients receiving ribavirin during antiviral treatment for chronic HCV infection. Orv. Hetil., 2011, 152, 876–881.


Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 685
Author(s):  
Emmanuelle V. LeBlanc ◽  
Youjin Kim ◽  
Chantelle J. Capicciotti ◽  
Che C. Colpitts

Chronic hepatitis C virus (HCV) infections continue to be a major contributor to liver disease worldwide. HCV treatment has become highly effective, yet there are still no vaccines or prophylactic strategies available to prevent infection and allow effective management of the global HCV burden. Glycan-dependent interactions are crucial to many aspects of the highly complex HCV entry process, and also modulate immune evasion. This review provides an overview of the roles of viral and cellular glycans in HCV infection and highlights glycan-focused advances in the development of entry inhibitors and vaccines to effectively prevent HCV infection.


Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 597
Author(s):  
Bianca Cerbu ◽  
Stelian Pantea ◽  
Felix Bratosin ◽  
Iulia Vidican ◽  
Mirela Turaiche ◽  
...  

Background and Objectives: The COVID-19 pandemic is an ongoing public health emergency. Patients with chronic diseases are at greater risk for complications and poor outcomes. The objective of this study was to investigate the liver function abnormalities and clinical outcomes in patients with COVID-19 and chronic hepatitis C. Materials and Methods: This retrospective, single-center study was conducted on a cohort of 126 patients with a history of hepatitis C, confirmed with COVID-19 between 01 April 2020 and 30 December 2020. Several clinical outcomes were compared between patients with active and non-active HCV infection, and the risks of liver impairment and all-cause mortality in active HCV patients were analyzed using a multivariate logistic regression model. Results: Among 1057 patients under follow-up for chronic HCV infection, 126 (11.9%) were confirmed with COVID-19; of these, 95 (75.4%) were under treatment or achieved SVR, while in the other 31 (24.6%), we found active HCV replication. There was a significantly higher proportion of severe COVID-19 cases in the active HCV group as compared to the non-active HCV group (32.2 vs. 7.3%, p < 0.001). Multivariate analysis showed that age, sex, alanine aminotransferase, C-reactive protein, procalcitonin, and HCV viral load were significant independent risk factors for liver impairment and all-cause mortality. The length of stay in hospital and intensive care unit for COVID-19 was significantly higher in patients with active HCV infection (p-value < 0.001), and a higher proportion of these patients required mechanical ventilation. Conclusions: Active HCV infection is an independent risk factor for all-cause mortality in COVID-19 patients.


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