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

Abstract

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.

Effect of Shenlingyigan decoction on inflammatory factors related to liver injury regulated by TLR3 signaling pathway

“…According to the research of Guedes and Yin [ 13 , 14 ] et al, TLR3 is associated with strong inflammation and liver damage. The viral load in the liver is positively correlated with the TLR3 gene, and activation of TLR3 in liver cells can induce the activation of IRF-3, thereby inhibiting the replication of hepatitis viruses (HBV, HCV, etc.).…”

Influence of polymorphic variations of IFNL, HLA, and IL-6 genes in severe cases of COVID-19

“…IFN-λ3, particularly IL-28B, may be associated with clinical severity in some pathologies such as hepatitis B, 73 as well as other viral infections. 74,75 In COVID-19, there is an association of various SNPs in monitoring the clinical condition of infected individuals and in sustained antiviral action in the regulation of the immune response. 76 The genotypes of rs12979860 (CC) and rs12980275 (AA) were considered strong contributors to resistance in SARS-CoV-2 infection; 73,76 however, among this variation, there was unfavorable genotypic discrimination with influence on clinical progression to severity in the rs12979860 (TT) SNP, which is the same genotype associated with disease aggravation such as hepatitis C in the development of hepatocellular carcinoma.…”

Toll-like receptor 3 gene regulates cataract-related mechanisms via the Jagged-1/Notch signaling pathway

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