The Study On Relationship Between Polymorphisms Of IL-12and Plasma Level Of Associated Cytokines And Outcome Of Chronic HCV Infection

Objective: Hepatitis C virus (HCV) is a major causative factor of chronichepatitis with roughly180million of the population infected worldwide, andthe prevalence of HCV antibody is3.2%in China. Approximately50%~80%of the patients infected with HCV will develop chronic infection. ChronicHCV infection can progress towards more severe outcomes,10%~15%in theform of cirrhosis after20years and1%~7%in the form of hepatocellularcarcinoma annually in patients with cirrhosis. HCV infection is a serious andgrowing threat to public health. There is no effective vaccine for prevention ofHCV infection, with the interferon (IFN) in combination with ribavirin (RBV)remaining the clinical standard regimen. Because the IFN/RBV treatmentduration for HCV is long and it has multiple adverse reactions, only38%~60%of chronic hepatitis C (CHC) patients can achieve sustainedvirological response (SVR), there still being a large part of patients withpersistent viral infection. The pathogenesis for HCV is complexity, someresearch showed that HCV infection in different clinical outcomes isassociated with some cytokine gene polymorphisms. In addition, the immunestatus of patients is related to chronic HCV infection/virological response. Aswell as other viral infections, HCV infection can induce activations of thenon-specific immune responses and specific immune response. And in theinduction and activation of HCV-specific cellular immune responses, Th1cells play an important role.Method: Two hundred and fifty-six patients with chronic HCV infectionwere selectied from Third Hospital of Hebei Medical University, the FifthHospital of Shijiazhuang City, Bethune International Peace Hospital, XingtaiPeople’s Hospital and Handan Infections Disease Hospital from January2011to September2013. Study on relationship between polymorphisms of IL-12B and plasma level of associated cytokines and outcome of chronic1Relations between IL-12rs3212227polymorphism and HCV infectionTwo hundred and fifty-six CHC patients and129healthy controls wereinvolved for analysis of IL-12rs3212227polymorphisms by TaqMan system.The relationship of the alleles and genotypes distributions of IL-12B betweenthe CHC patients and the healthy controls was analysed.2Study on the relationship of plasma IL-12, IL-10, IFN-γ level andHCV infection status and treatment responseFifty-two CHC patients (18~65years old) were treated with interferoncombined with ribavirin for up48weeks Forty age and gender matchedhealthy subjects were used as controls and40HCV spontaneous clearancesubjects. Levels of plasma Interleukin-12(IL-12), IL-10and IFN-γ wereevaluated by enzyme linked immunosorbent assay (ELISA) in healthy controls,spontaneous clearance group and patients at baseline,12weeks followingtreatment and24weeks after the end of treatment.Results:1. Levels of plasma IL-12, IL-10,IFN-γLevel of plasma IL-12was significantly lower in CHC patients comparedwith the control subjects and spontaneous clearance group (P <0.001). Therewas no significant difference among the control subjects and spontaneousclearance group (P>0.05). Plasma IL-12level was increased at12weeksfollowing treatment and24weeks after the end of treatment in the group ofpatients achieved SVR (P <0.001). For the CHC patients with non-SVR, therewas no significant difference during treatment (P>0.05). Compared with thepatients with SVR, the level of plasma IL-10was significantly higher inpatients unachieved SVR at baseline,12weeks following treatment and24weeks after the end of treatment (P <0.01, P <0.05, P <0.001). For the twogroup of CHC patients, there was no significant difference during treatment,respectively (P>0.05). Level of plasma IFN-γ was significantly lower inCHC patients compared with the control subjects and spontaneous clearancegroup (P <0.001). And there was higher level of IFN-γ observed in the spontaneous clearance group than the control subjects (P <0.01). Comparedwith the with non-SVR, the CHC patients with SVR produced higher levelIFN-γ at baseline,12weeks following treatment and24weeks after the end oftreatment (P <0.001). There was no significant difference between CHCpatients with non-SVR at each time point during treatment (P>0.05).2IL-12B gene polymorphismThere was no significant difference neither in distribution of IL-12rs3212227A/C (χ2=0.573, P=0.449) nor in distribution of AA (32%vs38%), AC (48%vs42%), CC (20%vs20%) genotypes (χ2=1.61, P=0.447)between the patients with chronic HCV infection and the healthy controls.Among95patients were tested HCV genotypes. As well as the alleles (χ2=2.718, P=0.099) and genotypes (χ2=2.645, P=0.267) distribution of IL-12rs3212227did not show any significant differences between HCV genotype1and genotype2infected patients. And between chronic HCV infection ingroup of SVR and that in non-SVR there was no significant differencesneither in distributions of IL-12rs3212227A/C (χ2=1.23, P=0.267) nor indistribution of AA (37%vs.27.4%）、AC（45%vs.51.6%）、CC（18%vs.21%）genotypes (χ2=1.582, P=0.453).Conclusion:1IL-12B polymorphisms may have no significant association with thesusceptibility and prognosis of chronic HCV infection in Chinese population.2The plasma level of IL-12and IFN-γ was increased during antiviraltreatment in CHC patients with SVR.3The plasma level of IL-10is expected to become a predictor ofspontaneous clearance in HCV patients.