Study On HCV Infection Characteristics And The Association Of NF-kappa B Genes Polymorphisms With HCV Susceptibility And Outcomes In High-risk Chinese Populations

Section 1 Analysis of biochemical characteristics in HCV infected patients[Background] Hepatitis C virus(HCV)infection as one of blood borne diseases can easily cause chronic hepatitis C,and then progress to end-stage liver diseases such as liver cirrhosis and liver cancer.Hepatitis C is an immune-related disease,which not only affects the liver,but also affects other organs of the body.After infection,it involves multiple reactions of different systems in human’s body.Many studies have found that HCV is hepatotropic,and also can replicate in peripheral blood cells,kidneys,and bone marrow.The virus also has a certain degree of lymphocyte tropism.The white blood cell count,classification,platelet count,and other blood biochemical parameters of HCV patients will change after infection.The biochemical characteristics of different states after HCV infection are important for assessing disease progression and patient prognosis.[Objective] To screen biochemical markers related to liver function and compare the physiological status of patients with different HCV infection outcomes.Besides,to identify biochemical indicators that are most suitable for assessing disease progression and patient prognosis.[Methods] Epidemiological investigations were conducted to collect information on 130 cases of HCV self-limiting removal and 173 cases of persistent infection.We collected 10 m L of venous blood in the morning of each subject on an empty stomach and used appropriate instruments to detect blood routine,liver function,coagulation function,and thyroid function.Partial correlation analysis was used to find related biochemical indexes of liver function and their relationship with HCV infection status.[Results] Partial correlation analysis after adjusting for age and sex showed that there was a positive correlation between lymphocyte count(LYMPH),monocytes(MONO),prothrombin time(PT)with ALT and AST.There were significant differences between the blood routine,liver function and coagulation function of different HCV infection outcomes.Stepwise regression analysis of age,gender,and above differential biochemical indicators showed that there was a correlation between ALT,ADA,and HCV RNA load(P=0.008,P=0.032).[Conclusion] LYMPH,MONO,and PT are biochemical markers related to liver function.There are significant differences in blood routine,liver function,and coagulation function between the HCV self-limited elimination group and the HCV persistent infection group.ALT and ADA are related to HCV RNA load.Section 2 Association of NF-κB Gene Polymorphisms with HCV infection Susceptibility and Outcomes in high-risk Chinese populations[Background] It is estimated that there are more than 185 million people infected with hepatitis C virus(HCV)world widely.In China,the prevalence of HCV accounts for about 1.6% of the whole population.More than 70% of HCV-infected individuals will not be able to spontaneously clear the virus and will develop chronic hepatitis C(CHC),cirrhosis and primary hepatocellular carcinoma.The multiple outcomes after HCV infection are the results of a combination of host genetic factors and viral factors.NF-κB plays specific roles in both initial and adaptive immunity process.NF-κB can be activated by a wide range of stimuli,such as bacteria,viral antigens,cytokines,and oxidative stress,triggering many inflammatory regulators.Thus,abnormal activation and aberrant regulation of the NF-κB signaling pathway genes may lead to certain autoimmune diseases,inflammation,and malignancies;it may also be involved in the two-way regulation of virus escape and inactivation in certain infections.There is a significant association between single nucleotide polymorphisms(SNPs)of NF-κB signaling pathway genes and numerous diseases.Based on the above-mentioned antiinfectious effects of NF-κB in the host immune response,mutations in the NF-κB signaling pathway may affect HCV infection course and prognosis.[Objective] To explore the possible role of NF-κB signaling pathway gene mutation in the progression and prognosis of HCV infection.[Methods] Multivariate logistic regression model was used to analyze the associations of rs230530,rs3774963,rs1056890,rs11820062 at NF-κB signaling pathway genes with HCV susceptibility and infection outcomes in total of 2581 highrisk individuals.Three models(additive model,dominant model and recessive model)were used to analyze the association between each SNP and HCV susceptibility and infection outcomes.[Results] Logistic regression analysis showed that the risk of HCV infection in individuals carrying the rs11820062 TT genotype was significantly higher(P=0.002) after adjusting for age,sex,and route of infection.In the additive and dominant models,the relationship between the rs11820062 T allele and the susceptibility to HCV infection remained statistically significant(P=0.002,P=0.003).In the dominant model,the distribution of the rs230530 C allele was significantly different between the control and HCV infected groups(P=0.005).We used the Cochran-Armitage trend test to analyze the cumulative effects of the rs11820062 T allele and the rs230530 C allele on HCV susceptibility.The results showed that individuals carrying more dangerous alleles were at higher risk of HCV infection,and carrying the three risk alleles had the highest risk of the disease(OR=1.894,95% CI = 1.230-2.758).[Conclusion] The genetic variations of NF-κB signaling pathway are associated with HCV susceptibility in high-risk Chinese populations.The rs11820062 T and rs230530 C alleles significantly increase the risk of HCV infection.