scholarly journals Intrahepatic TLR3 and IFNL3 Expressions Are Associated with Stages of Fibrosis in Chronic Hepatitis C

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1103
Author(s):  
Keyla Santos Guedes de Sá ◽  
Ednelza da Silva Graça Amoras ◽  
Simone Regina Souza da Silva Conde ◽  
Maria Alice Freitas Queiroz ◽  
Izaura Maria Vieira Cayres-Vallinoto ◽  
...  

An inefficient immune response against the hepatitis C virus (HCV), combined with viral evasion mechanisms, is responsible for the chronicity of infection. The need to evaluate the innate mechanisms of the immune response, such as TLR3 and IFN-λ3, and their relationship with the virus–host interaction is important for understanding the pathogenesis of chronic hepatitis C. The present study aimed to investigate the gene expressions of TRL3 and IFNL3 in liver tissue, seeking to evaluate whether these could be potential biomarkers of HCV infection. A total of 23 liver biopsy samples were collected from patients with chronic HCV, and 8 biopsies were collected from healthy control patients. RNA extraction, reverse transcription and qPCR were performed to quantify the relative gene expressions of TLR3 and IFNL3. Data on the viral load; AST, ALT, GGT and AFP levels; and the viral genotype were collected from the patients′ medical records. The intrahepatic expression of TLR3 (p = 0.0326) was higher in chronic HCV carriers than in the control group, and the expression of IFNL3 (p = 0.0037) was lower in chronic HCV carriers than in the healthy control group. The expression levels of TLR3 (p = 0.0030) and IFNL3 (p = 0.0036) were higher in the early stages of fibrosis and of necroinflammatory activity in the liver; in contrast, TLR3 and IFNL3 expressions were lower in the more advanced stages of fibrosis and inflammation. There was no correlation between the gene expression and the serum viral load. Regarding the initial METAVIR scale scores, liver transaminase levels were lower in patients with advanced fibrosis when correlated with TLR3 and IFNL3 gene expressions. The results suggest that in the early stages of the development of hepatic fibrosis, TLR3 and IFN-λ3 play important roles in the antiviral response and in the modulation of the tolerogenic liver environment because there is a decrease in the intrahepatic expressions of TLR3 and IFNL3 in the advanced stages of fibrosis, probably due to viral evasion mechanisms.

JMS SKIMS ◽  
2010 ◽  
Vol 13 (2) ◽  
pp. 39-40
Author(s):  
Showkat Ali Zargar

Chronic hepatitis C is highly prevalent with prevalence rate of around 3% involving about 180 million people worldwide, despite major advances in its understanding of viral 1 pathogenesis and significant evolution in antiviral therapies. Most of the patients develop chronic infection because the virus evades the host immune response in majority of patients. Chronic HCV infection can lead to cirrhosis and hepatocellular carcinoma. Complications of HCV-related cirrhosis are the leading indication for liver transplantation in United States and Europe...... J Med Sci 2010;13(2): 39-40.


2013 ◽  
Vol 18 (5) ◽  
pp. 9-14
Author(s):  
T. V Sologub ◽  
V. V Tsvetkov ◽  
E. G Deeva ◽  
I. I Tokin

In order to evaluate the efficiency and safety of using the drug Ingaron in treatment ofpatients with chronic hepatitis C (CHC) an open, randomized, control comparative study has been performed. We examined of 132 CHC patients aged from 18 to 58 years. All patients were selected into 3 groups depending on the type of therapy. The following drugs: Ribavirin, Alfarona, Ingaron were included in regimens of therapy. The course of the disease in examined CHC patients was characterized by mild clinical symptoms, the presence of the expressed cytolytic syndrome more than in half of the patients (50.8%), high levels of «viral load» in 61.6% of patients with the establishment of a direct correlation between high ALT and viremia levels (r=+0,67). The average level of «viral load» in patients infected with no-1 genotype of hepatitis C, at the start of therapy was 1,4 times higher than in those with genotype 1, amounting to 1,8 x 106 and 1,3 x 106 IU/ml, respectively. Patients infected with HCV genotype 1 and receiving therapy with Ingaron for 24 and 12 weeks, achieved sustained viral response in 65,0% and 80,0% of cases whereas patients infected with «no 1» genotype - in 73,9%, and 84,6% of cases, respectively. At the same time, in patients from the control group the sustained viral response was observed only in 56,0% and 60,0% of cases (1 and «no 1» genotypes, respectively). The inclusion of Ingaron into the classical medical regimen was accompanied by a reduction in the incidence of adverse reactions during treatment.


2020 ◽  
Author(s):  
Angélica Menezes Santiago ◽  
Ednelza da Silva Graça Amoras ◽  
Maria Alice Freitas Queiroz ◽  
Simone Regina Souza da Silva Conde ◽  
Izaura Maria Vieira Cayres-Vallinoto ◽  
...  

Abstract Background: Genetic changes may induce dysregulated cytokine production and affect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-inflammatory cytokines determines the outcome of infection. This study evaluated the TNFA -308G>A and IL10 -1082A>G polymorphisms in the susceptibility and progress of chronic hepatitis CMethods: The study included 101 samples from patients with chronic hepatitis C and 300 samples from healthy donors. Polymorphisms were typed by real-time PCR and were analyzed for associations with histopathological parameters (according to METAVIR classification) and HCV viral load. Results: The polymorphic genotype for the TNFA -308G>A variant was not present in the group of patients with chronic hepatitis C and was associated with protection against HCV infection (p = 0.0477). Patients with the polymorphic genotype of the IL10 -1082A>G polymorphism had higher HCV viral load than wild-type patients (p = 0.0428). Neither polymorphism was associated with different levels of necroinflammatory activity or fibrosis scores. Conclusion: The polymorphic genotype at TNFA -308G>A protected against chronic HCV infection, and the polymorphic genotype at the IL10 -1082A>G variant was associated with viral persistence.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10723
Author(s):  
Mirela Pavicic Ivelja ◽  
Kresimir Dolic ◽  
Leida Tandara ◽  
Nikola Perkovic ◽  
Antonio Mestrovic ◽  
...  

Although liver cirrhosis and hepatocellular carcinoma are major consequences of hepatitis C (HCV), there has been an increasing number of studies examining extrahepatic manifestations, especially those caused by systemic chronic inflammation and metabolic complications that might predispose HCV patients to atherosclerosis and ischemic cerebrovascular disease (CVD). The aim of our study was to assess E-selectin, VCAM-1, ICAM-1 and VEGF-A serum levels in patients with chronic HCV infection and to correlate them with cerebrovascular reactivity. A blood sample was taken from eighteen patients with chronic hepatitis C infection and from the same number of healthy blood donors in the control group. The aim was to analyse markers of endothelial dysfunction and to correlate them with cerebrovascular reactivity expressed as breath-holding index (BHI) determined using transcranial color Doppler. The obtained results revealed significant differences between the groups in all endothelial markers except for the E selectin. While the ICAM-1 and sVCAM-1 were significantly increased in the hepatitis group, VEGF-A was significantly decreased. A significant reduction of 0.5 (95% CI 0.2, 0.8) in the mean BHI was found in the hepatitis group (mean BHI 0.64) compared to controls (mean BHI 1.10). No significant association between the BHI and any of the endothelial markers was found in the control group, while in the hepatitis group, the scatter plot of ICAM-1 vs BHI suggested that the association might be present. In conclusion, the results of this study confirm an association between a chronic HCV infection and altered cerebrovascular reactivity as well as higher levels of markers of endothelial activation (ICAM-1, VCAM-1) as possible indicators of an increased CVD risk.


2021 ◽  
Author(s):  
Angélica Menezes Santiago ◽  
Ednelza da Silva Graça Amoras ◽  
Maria Alice Freitas Queiroz ◽  
Simone Regina Souza da Silva Conde ◽  
Izaura Maria Vieira Cayres-Vallinoto ◽  
...  

Abstract Genetic changes may induce dysregulated cytokine production and affect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-inflammatory cytokines determines the outcome of infection. This study evaluated the TNFA − 308G > A and IL10 -1082A > G polymorphisms in the susceptibility and progress of chronic hepatitis C. The study included 101 samples from patients with chronic hepatitis C and 300 samples from healthy donors. Polymorphisms were typed by real-time PCR and were analyzed for associations with histopathological parameters (according to METAVIR classification) and HCV viral load. The polymorphic genotype for the TNFA − 308G > A variant was not present in the group of patients with chronic hepatitis C and was associated with protection against HCV infection (p = 0.0477). Patients with the polymorphic genotype of the IL10 -1082A > G polymorphism had higher HCV viral load than wild-type patients (p = 0.0428). Neither polymorphism was associated with different levels of necroinflammatory activity or fibrosis scores. The polymorphic genotype at TNFA − 308G > A protected against chronic HCV infection, and the polymorphic genotype at the IL10 -1082A > G variant was associated with viral persistence.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Alessandro Grasso ◽  
Federica Malfatti ◽  
Gabriella Andraghetti ◽  
Simona Marenco ◽  
Chiara Mazzucchelli ◽  
...  

Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders.Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment.Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P=0.033and 0.048, resp.) in patients who achieved an early viral load decay (EVR), a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR.Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.


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.


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.


2012 ◽  
Vol 24 (12) ◽  
pp. 1393-1399 ◽  
Author(s):  
Hasan S. Zeki Aksu ◽  
Behice Kurtaran ◽  
Yusuf Onlen ◽  
Mustafa Namiduru ◽  
Ahmet C. Inkaya ◽  
...  

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