Published online Jan 27, 2021. doi: 10.4254/wjh.v13.i1.109
Peer-review started: July 31, 2020
First decision: October 23, 2020
Revised: November 9, 2020
Accepted: November 17, 2020
Article in press: November 17, 2020
Published online: January 27, 2021
Hepatitis C virus (HCV) infection is a public health concern worldwide. Several factors, including genetic polymorphisms, may be evolved in the progression of HCV infection to liver diseases. Interferon lambdas (IFNLs) modulate the immune response during viral infections. IFNLs induce antiviral activity, interfering in the viral replication by promoting the expression of several genes that regulate immunological functions. The interferon lambda-4 (IFNL4) rs12979860 polymorphism, which is characterized by a C to T transition in intron 1, is associated with spontaneous and treatment-induced clearance of HCV infection and may play a role in the development of HCV-associated liver diseases, including hepatocellular carcinoma (HCC).
To investigate the association of IFNL4 rs12979860 polymorphism with fibrosis, cirrhosis, and HCC in patients with chronic HCV infection.
This study was comprised of 305 chronic HCV-infected patients (53 fibrosis, 154 cirrhosis, and 98 HCC cases). The control group was comprised of 260 HCV-negative healthy individuals. The IFNL4 rs12979860 polymorphism was genotyped using the TaqMan assay. Fibrosis was diagnosed based on liver biopsy findings, while cirrhosis was diagnosed through clinical, laboratory, anatomopathological, and/or imaging data. HCC was diagnosed through imaging tests, tumor, and/or anatomopathological markers.
The T allele was observed in the three groups of patients (fibrosis, cirrhosis, and HCC) at a significantly higher frequency when compared with the control group (P = 0.047, P < 0.001, and P = 0.01, respectively). Also, genotype frequencies presented significant differences between the control group and cirrhosis patients (P < 0.001) as well as HCC patients (P = 0.002). The risk analysis was performed using the codominant and dominant T allele models. In the codominant model, it was observed that the CT genotype showed an increased risk of developing cirrhosis in comparison with the CC genotype [odds ratio (OR) = 2.53; 95% confidence interval (CI): 1.55-4.15; P < 0.001] as well as with HCC (OR = 2.54; 95%CI: 1.44-4.56; P = 0.001). A similar result was observed in the comparison of the TT vs CC genotype between the control group and cirrhosis group (OR = 2.88; 95%CI: 1.44-5.77; P = 0.001) but not for HCC patients. In the dominant T allele model, the CT + TT genotypes were associated with an increased risk for progression to cirrhosis (OR = 2.60; 95%CI: 1.63-4.19; P < 0.001) and HCC (OR = 2.45; 95%CI: 1.42-4.31; P = 0.001).
These findings suggest that the T allele of IFNL4 rs12979860 polymorphism is associated with the development of cirrhosis and HCC in chronic HCV-infected patients.
Core Tip: Hepatitis C virus (HCV) infection is a major public health problem worldwide as the infection progresses to severe chronic liver diseases in many patients. Interferon lambdas modulate the immune responses against infections, including the antiviral activity by promoting the expression of several genes related to immunological functions. The interferon lambda-4 rs12979860 (C/T) polymorphism, which is associated with spontaneous and treatment-induced clearance of HCV, plays a pivotal role in the host response to HCV-associated liver diseases. In this case-control study, the rs12979860 T allele was found to be associated with the development of cirrhosis and hepatocellular carcinoma in chronic HCV-infected patients.