Investigating the role of killer cell immunoglobulin-like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection.

The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.

KIR2DL4/HLA-G polymorphisms were associated with HCV infection susceptibility among Chinese high-risk population.

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 (ptrend < 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 might affect the innate immune responses by regulating KIR2DL4/HLA-G transcription and translation play a potential role in HCV infection.

Efficacy and Safety of Direct-Acting Antivirals in Kidney Transplantation From HCV-Viremic Donors to Negative Recipients: A Meta-Analysis.

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. Methods: Multiple 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. Results: In 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. Conclusion: This comprehensive analysis showed the high efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to HCV-negative recipients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=246541.

Effects of policies and containment measures on control of COVID-19 epidemic in Chongqing.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving disease that spreads through the respiratory system and is highly contagious. In March 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. In China, the pandemic was controlled after 2 mo through effective policies and containment measures. Describing the detailed policies and containment measures used to control the epidemic in Chongqing will provide a reference for the prevention and control of COVID-19 in other areas of the world. AIM: To explore the effects of different policies and containment measures on the control of the COVID-19 epidemic in Chongqing. METHODS: Epidemiological data on COVID-19 in Chongqing were prospectively collected from January 21 to March 15, 2020. The policies and prevention measures implemented by the government during the epidemic period were also collected. Trend analysis was performed to explore the impact of the main policy measures on the effectiveness of the control of COVID-19 in Chongqing. RESULTS: As of March 15, the cumulative incidence of COVID-19 in Chongqing was 1.84/100000 (576 cases) and the infection fatality rate was 1.04% (6/576). The spread of COVID-19 was controlled by effective policies that involved establishing a group for directing the COVID-19 epidemic control effort; strengthening guidance and supervision; ensuring the supply of daily necessities and medical supplies and equipment to residents; setting up designated hospitals; implementing legal measures; and enhancing health education. Medical techniques were implemented to improve the recovery rate and control the epidemic. Policies such as "the lockdown of Wuhan", "initiating a first-level response to major public health emergencies", and "implementing the closed management of residential communities" significantly curbed the spread of COVID-19. Optimizing the diagnosis process, shortening the diagnosis time, and constructing teams of clinical experts facilitated the provision of "one team of medical experts for each patient" treatment for severe patients, which significantly improved the recovery rate and reduced the infection fatality rate. CONCLUSION: The prevention policies and containment measures implemented by the government and medical institutions are highly effective in controlling the spread of the epidemic and increasing the recovery rate of COVID-19 patients.