Background and Aims: Genetic polymorphisms of Toll-like receptors (TLRs) have been proposed to affect susceptibility to HCV infection and progression to end-stage liver disease. This study was conducted to clarify the association of SNPS of TLR2 and TLR4 with clinical outcome of hepatitis C, response to treatment and development of HCC. Methods: The current study examined 3295 individuals from 725 families that were categorized into groups comprising chronic HCV (CH), spontaneous viral clearance (SC) and control subjects. Treated patients were classified into responders (RT) and non-responders (NRT). In addition, patients with liver cirrhotic (LC), and hepatocellular carcinoma (HCC) were also included. All subjects were genotyped for five single nucleotide polymorphisms (SNPs) of TLR2 and four SNPs of TLR4 and their haplotypes using allelic discrimination real-time PCR. Results: Results demonstrated strong association with allele A of rs13105517 of TLR2 and allele C of rs10116253 of TLR4 with CH in comparison to SC group. However, The peak of risk of HCC was observed with allele C of rs3804099 of TLR2 and C allele of rs10116253 TLR4 (p < 0.001).A strong association was found with allele T of rs1816702 of TLR2 and allele A of rs5030728 of TLR4 in non responder group in comparison to responders (p < 0.001). Haplotypes CAGT of TLR4 and ATAC of TLR2 showed significant association with CH and HCC groups in comparison to other groups. Conclusions: This study shows an association of minor alleles of TLR2 and TLR4 with outcome of HCV infection, response to therapy and development of HCC in cirrhotic patients.

Background: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are linked with functional modification of cytokine responses. In chronic hepatitis C virus (HCV) infection, studies of TLR polymorphisms have primarily targeted receptor pathways implicated in viral immune responses. We hypothesized that one or more variant(s) of TLR3, TLR7 and TLR8 are associated with different outcomes of HCV infection. Materials & methods: A total of 3368 subjects from 850 families were recruited and divided into three main groups categorized as chronic HCV CHC spontaneous viral clearance (SVC), and controls. All individuals were genotyped for three SNPs for TLR3, two SNPs for TLR7, and two SNPs for TLR8 using allelic discrimination real-time PCR. Results: Carriage of the C allele in three SNPs of TLR3 (rs3775290, rs3775291, and rs5743312), the C allele in TLR7 (rs3853839) in females only, and the C allele in TLR8 (rs3764879) in males only were significantly higher in SVC group than CHC group (P < 0.001), while carriage of the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both males and females were significantly higher in CHC infection more than SVC group (P < 0.001). Conclusion: The C allele is protective of HCV in TLR3, TLR7 (rs3853839) in females only, and TLR8 (rs3764879) in males only, while risk of infection is linked to the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both sexes.

Background: Limited experimental and clinical evidence suggests a potential role for sofosbuvir/daclatasvir in treating COVID19. we aim to evaluate the efficacy of generic sofosbuvir/daclatasvir in treating COVID-19 patients with pneumonia. Research design and methods: This multicenter prospective study involved 174 patients with COVID-19. Patients were randomized into two groups. Group A (96 patients) received sofosbuvir (400 mg)/ daclatasvir (60 mg) for 14 days in combination with conventional therapy. Group B (78 patients) received conventional therapy alone. Clinical, laboratory and radiological data were collected at baseline, after 7, 14 and 28 days of therapy. Primary endpoint was rate of clinical/virological cure. Results: A lower mortality rate was observed in group (A) (14% vs 21%, P = 0.07). After one month of therapy, no differences were found in rates of ICU admission, oxygen therapy or ventilation. Additionally, a statistically significant shorter duration of hospital stay (9% vs 12%, P <0.01) and a faster achievement of PCR negativity at day 14 (84% versus 47%, P <0.01) were noticed in group (A). Conclusion: Adding sofosbuvir/daclatasvir to conventional therapy of COVID-19 is promising. Their use is associated with shorter hospital stay, faster PCR negativity and may be reduced mortality.