Correlation between IL28B/TLR4 genetic variants and HCC development with/without DAAs treatment in chronic HCV patients

Abstract

In Egypt, Sofosbuvir (SOF) in combination with Dataclasvir (DCV) is the broadly used DAAs with excellent therapeutic profile. This study is designed to explore the relation between IL28B/TLR4 genetic variants and each of the followings; HCC development post SOF/DCV treatment, progression to HCC in naïve patients and SOF/DCV therapy outcome. A total of 493 blood samples were collected (controls ( n = 70); HCV patients treated with SOF/DCV ( n = 252) of whom 65 patients developed HCC, 187 patients didn't develop HCC (125 responders, 62 relapsers); naïve HCV patients ( n = 171) had early ( n = 48), late liver fibrosis ( n = 21) and HCC ( n = 102)). Both SNPs were genotyped using a TaqMan 5′ allelic discrimination assay. At IL28B rs12979860 SNP, the C allele was significantly correlating with the response rate more than T allele (OR 1.9, 95% CI 1.29–2.9, p = 0.004), while at TLR4 rs4986791 SNP, no association was found (OR 6.5, 95% 0.57–75.28, p = 0.09). Both SNPs couldn't detect the probability for HCC emergence after treatment. In naïve patients, the protective alleles were detected in their lowest frequency in HCC patients ( p = 0.1, for rs12979860 and, p = 0.001 for rs4986791). SOF/DCV combination improved SVR rates in HCV genotype 4a infected patients regardless of IL28B genotype, with the best rates in those lacking the T allele.

Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study

“…These SNPs have been associated with many diseases, including a variety of cancers, infections, inflammatory bowel disease, chronic obstructive pulmonary disease, asthma, and diabetes mellitus, showing either protective or aggravating function; however, most studies are relatively small, and results are contradictory [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Likewise, the aforementioned TLRs have been studied in a variety of liver diseases, such as hepatitis C, cirrhosis and HCC, with no definite role being established [ 25 , 36 , 37 ].…”

“…Likewise, TLR4 mutations showed no statistically significant correlation with duration of cirrhosis or HCC development. Regarding TLR4 SNPs and the occurrence of HCC, study results are contradictory, with various SNPs being associated with either increased or decreased probability for HCC development [ 36 , 37 , 44 , 45 , 46 , 47 , 48 , 49 ]. Likewise, the results are not consistent when Asp299Gly and Thr399Ile are associated with HCC development [ 36 , 44 , 45 , 46 ].…”

Insulin-like Growth Factor Initiates Hepatocellular Carcinoma in Chronic Hepatitis C Virus Patients through Induction of Long Non-coding Ribonucleic Acids AF085935

“…Liver cirrhosis and HCC are major complication of HCV chronic infection [21]. HCC is one of the most common solid tumors, which rated as the third cancerrelated mortality worldwide [22], [23]. Survival rate for HCC is very low due to lack of early diagnosis and reliable biomarkers, so new and accurate diagnostic biomarkers are needed.…”

Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha

“…The clinical trial with DAAs therapy combined with IFN-α – SPRINT-2 and ADVANCE trials – showed that rs12979860 affected the treatment outcome, and patients with CC genotype displayed 80% and 90% SVR in the respective trials ( Matsuura et al., 2014 ). Also, an IFN-free INFORM study of mericitabine as a monotherapy, or in combination with danoprevir, suggested that the IFNL3 genotypes may also predict viral kinetics ( Chu et al., 2012 ; Ramamurthy et al., 2018 ; Salum et al., 2020 ).…”