The Clinical Significant Of TNF-α System In Hepatitis C Infection And The Relationship Of Hepatitis C Virus Genotypes And TNF-α System

Objective:The infection of hepatitis c virus(HCV)was one of important topic in all the worlds,and it was main etiological factor of post- transfusion hepatitis.About 50%～85%of acute HCV infected persons would become persistent infection,and it was important factor to cause hepatic cirrhosis and liver cancer.After human body was infected with HCV,the immune system of host was activated,then product and release various kinds of cytokines.One of the important cytokines was tumor necrosis factor-alpha(TNF-α).TNF-αcould induce that hepatic cells producted other cytokines,so a great quantity cytokines occurrented in the hepatic tissue, all of these made activation of cytokines network.These cytokines promoted inflammatory reaction,mediated liver injury,induced differentiation and generation of all kinds of cells.These made the inflammation of hepatic cell continue existence.At the same time,because HCV RNA polymerase was short of check function,HCV genome presented upstair heterogeneity,and HCV emerged quasispecies variation easily.The new quasispecies influenced recognition capability of antibody and T cell,breakdowned the humoral immunity and cellular immunity of host,affected creation and releasing of cytokines and escaped immune clearance.We analyzed the levels of TNF-αand soluble tumor necrosis factor receptorâ…¡(sTNFR₂)in different pathogenetic condition in HCV infected persons.At the same time,we genotyped HCV using restriction fragment length orphism(RFLP),approached gene distribution feature of hepatitis C in Shanxi province,analyzed the relationship of genotype and TNF-αsystem,provided reference proof for formulating treatment plan and judgementing prognosis.Methods:(1)Collection of cases and serums:To collect the clinical informations and serum of 62 patients who were diagnosed of chronicity hepatitis C.The clinical informations include common dates,liver functions and HCV RNA quantitations.Twenty health persons are contrast.(2)To detect serum TNF-αand sTNFR₂,analyze the role of TNF-αsestem in HCV infection.(3)To extract RNA of each sample,reverse transcription,design primers and amplify 5' non-coding region(5'NCR).To cut 5'NCR into different length clips using incision enzyme Haeâ…¢and Bsh1236â… and determine genotypes.(4)To analyze the relationship of TNF-α,sTNFR₂ and genotype,approach the part mechanism of genotype.Results.(1)The levels of TNF-α,sTNFR₂ and sTNFR₂/TNF in midrange and severe patients were higher than health persons,each of three groups were different,the difference was significance in statistics(P＜0.001).(2)The levels of TNF-α,sTNFR₂ and sTNFR₂/TNF had positive correlation with the levels of ALT and TBIL,the difference was significance in statistics(P＜0.001),had positive correlation with the levels of HA andâ…£C,the difference was significance in statistics(P＜0.05).(3)The levels of TNF-α,sTNFR₂ and sTNFR₂/TNF had no statistical difference when HCV RNA semiquantitative was 80～,10³ï½ž,10⁴～,10⁵～copies/ml, but when HCV RNA was 10⁶～copies/ml,the levels of TNF-α,sTNFR₂ and sTNFR₂/TNF were higher than others and the difference wss significance in statistics.(4)60 patients out of the total 62 were tested genotype.43 of them were infected with genotype 1b(69.4%),type 2a account for 22.6%(14/62),and 1b/2a mixed-type was 1.6%(1/62),and 1 sera was type 1a,1 sera was type 3a,2 were not tested.The levels of TNF-α,sTNFR₂ and sTNFR₂/TNF in 1b type were higher than them in 2a type,the difference was significance in statistics(P＜0.001).Conclusion:The levels of TNF-α,sTNFR₂ and sTNFR₂/TNF have apparente positive correlation with pathogenetic condition.TNF-αsystem can reflect immune reaction and liver cells injury of organism,and it is index of immunological reaction and judgement prognosis. The levels of TNF-α,sTNFR₂ and sTNFR₂/TNF are high accordingly when the virus load is high.HCV is inductor of TNF-α,which can direct stimulus macrophage and make TNF-αrelease.The levels of TNF-α,sTNFR₂ and sTNFR₂/TNF in lb patients are higher then 2a type, this is maybe important factor of pathogenetic condition's severity in 1b patients.Genotype 1b is the dominance strain in Shanxi province,next one is genotype 2a.