Background:With the development of direct-acting antiviral agents (DAAs), the research on kidney transplantation from Hepatitis C virus (HCV)-viremic donors to HCV-negative recipients has grown. The objective of this comprehensive analysis was to evaluate the efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to negative recipients.MethodsMultiple databases were searched for a systematic and comprehensive up to March 2022. The primary outcomes included the percentage of sustained virological response at week 12 after the end of treatment (SVR12), adverse events (AEs; any grade), and severe adverse events (SAEs) as the endpoints. Publication bias was examined by using the funnel plots and Egger's test.ResultsIn total, 16 studies with 454 subjects were included in the study and the pooled estimate of SVR12, AEs, and SAEs rates were 100.0% (95% CI: 99.2-100.0), 1.9%(95%CI: 0.0-4.9), and 0.0% (95%CI: 0.0-1.5). Subgroup analysis showed that pooled SVR12 rates were 100.0% (95%CI: 99.6-100.0) for genotype (GT)1a and 96.3% (95%CI: 83.3-100.0) for GT2; 100.0% (95%CI: 98.9-100.0) for DAAs treatments; and 100.0% (95%CI: 98.2-100.0) for prophylaxis subgroup. Egger's tests showed that no publication bias was found in this study.ConclusionThis comprehensive analysis showed the high efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to HCV-negative recipients.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=246541.

Killer-cell immunoglobulin-like receptors 2DL4 (KIR2DL4) and the human leukocyte antigen class I-G (HLA-G) display vital parts in immune responses against hepatitis C virus (HCV) infection. We select four potentially functional single nucleotide polymorphisms (SNPs) of KIR/HLA to explore the associations between KIR2DL4/ HLA-G genetic variants and HCV infection results. In the present case-control study, a total of 2225 HCV-infected high-risk subjects, including 1778 paid blood donors (PBD) and 447 drug users were consecutively recruited before treatment from 2011 to 2018. KIR2DL4-rs660773, KIR2DL4-rs660437, HLA-G-rs9380142, and HLA-G-rs1707 SNPs were sorted as genotypes in the subdivided groups, involving 1095 uninfected controls subjects, 432 spontaneous HCV clearance subjects and 698 HCV persistent infection subjects. After genotyping experiments using the TaqMan-MGB assay, modified logistic regression was used to calculate the correlation among the SNPs and HCV infection. The SNPs were functionally annotated using bioinformatics analysis. Following adjusting by age, sex, alanine aminotransferase, aspartate aminotransferase, IFNL3-rs12979860, IFNL3-rs8099917, and the infection route, the logistic regression analysis discovered that KIR2DL4-rs660773 and HLA-G-rs9380142 were correlated with vulnerability to HCV infection (all p < 0.05). In a locus-dosage way, compared with subjects carrying the rs9380142-AA or rs660773-AA genotypes, subjects with rs9380142-AG or rs660773-AG/GG (all p < 0.05) were more vulnerable to HCV infection; the overall impact of their risk genotypes (rs9380142-AGrs660773-AG/GG) was correlated with an elevated incidence of HCV infection (p trend < 0.001). In the Haplotype analysis, patients with haplotype AG were more likely to contract HCV compared to those with the highest common AA haplotype (p = 0.002) were higher in susceptibility to infect HCV. The SNPinfo web server estimated that rs660773 is a transcription factor binding site, whereas rs9380142 is a potential microRNA-binding site. In two Chinese high-risk population (PBD and drug uesrs), KIR2DL4 rs660773-G and HLA-G rs9380142-G alleles polymorphisms are related to HCV susceptibility. KIR2DL4/HLA-G pathway genes

Background: Killer-cell immunoglobulin-like receptors 2DL4 ( KIR2DL4) and the human leukocyte antigen class I-G ( HLA-G) display vital parts in immune responses against HCV infection. We select four potentially functional SNPs of KIR/HLA to explore the associations between KIR2DL4/HLA-G genetic variants and HCV infection results. Methods: In the present case-control investigation, KIR2DL4-rs660773， KIR2DL4-rs660437， HLA-G-rs9380142, and HLA-G-rs1707 SNPs were sorted as genotype in a total of 2225 high-risk subjects, involving 1778 paid blood donors and 447 drug users. The SNPs were functionally annotated using bioinformatics analysis. Results: Following adjusting by age, sex, ALT, AST, IFNL4-rs12979860, IFNL4-rs8099917, and the infection route, the logistic regression analysis (LRA) discovered that KIR2DL4-rs660773 and HLA-G-rs9380142 were correlated with vulnerability to HCV infection (all P <0.05). In a locus-dosage way, compared with subjects carrying the rs9380142-AA or rs660773-AA genotypes, subjects with rs9380142-AG or rs660773-AG/GG (all P <0.05) were more vulnerable to HCV infection; the overall impact of their risk genotypes (rs9380142-AGrs660773-AG/GG) was correlated with an elevated incidence of HCV infection ( P<0.001). In the Haplotype analysis, patients with haplotype AG were more likely to contract HCV compared to those with the highest common AA haplotype ( P= 0.002) were higher in susceptibility to infect HCV.nThe SNPinfo web server estimated that rs660773 is a transcription factor binding site (TFBS), whereas rs9380142 is a potential microRNA-binding site. Conclusion: In the Chinese high-risk population, KIR2DL4 rs660773 and HLA-G rs9380142 polymorphisms are related to HCV susceptibility .