Association Of Immune Related Gene Polymorphism With HCV Spontaneous Clearance And Therapeutic Response

Section 1The association of HLA、IFN-λs gene polymorphism with HCV spontaneous clearance among high risk population[Objectives] This study aims to determine the association of HLA, IFN-λs polymorphism with the outcome of HCV infection and provide scientific basis to personalized treatment of HCV infection.[Methods] Case-control study was used and patients were divided into persistent infection group and control group. Genotyping of HLA, IFN-λs gene polymorphism was performed using Taqman-MGB probe technology. After the building of the database, we used Stata 12.0 software to analyze the association of the distribution of these genotypes with the outcome of HCV infection.[Results] Female patients older than 50 years were more in persistent infection group than spontaneous clearance group. People carrying rs4273729 CC genotype and rs 12979860 genotype TT genotype are more susceptible to persistent infection (additive model respectively OR= 1.77,95% CI= 1.44-2.78; OR= 1.51,95% CI= 1.06-2.13). There was no significant association between SNP rs 12980275 and rs368234815 polymorphic with HCV infection outcome (P> 0.05). Stratified analysis showed that among people whose age is less than 50 years old, male, hemodialysis population, drug users and HCV1 infection, rs4273729 mutation CC genotype and heterozygous GC genotypes in persistent infection group was significantly higher than spontaneous clearance group; In less than 50 years of age, and women with type 1 HCV infection, rs 12979860 CT and TT genotype frequency is higher in persistent infection group than spontaneous clearance group. Stepwise regression analysis showed that the route of infection, rs4273729, age and rs 12979860 were the independent predictive factors of chronic HCV infection, the area under the ROC curve was 0.685.[Conclusion] The single nucleotide polymorphism of HLA rs4273729 and IL28B rs 12979860 was likely to associate with HCV spontaneous clearance. Route of infection and age were also related to the outcome of HCV infection. However, further studies are needed to confirm our result.Section 2The association of HLA、IFN-λs gene polymorphism with therapeutic response among chronic hepatitis C patients[Objectives] We aim to determine the association of HLA、IFN-λs polymorphism with with therapeutic response among chronic hepatitis C patient and establish the effect prediction model.[Methods] A total of 354 cases of patients who completed pegylated interferon and ribavirin treatment were included. Serum HCV viral load, clinical parameters of baseline and 4,12,24,48 weeks and 24 weeks after treatment were collected. Genotyping of HLA、IFN-λs gene polymorphism was performed using Taqman-MGB probe technology.[Results] Patients who achived EVR was 284 cases, SVR was 240 cases. Baseline HCV viral load and total protein count in SVR group was significantly lower than non-SVR group. The ratio of blood AFP≤ 7.02, glucose< 6 in SVR group was significantly higher than non-SVR groaup. chronic hepatitis C patients who carry rs12979860 genotype TT, rs4273729 genotype CC, rs12980275 genotype GG genotype and rs368234815 △G/△G is less likely to achieve SVR (additive model respectively OR= 0.41,95% CI= 0.29-0.58; OR= 0.66,95% CI= 0.46-0.93; OR= 0.56,95% CI= 0.38-0.83; OR= 0.27,95% CI= 0.14-0.49). SNP rs12979860, rs368234815, baseline HCV-RNA, AFP, rs4273729 and GLU were independent predictive factors of SVR, the area under the ROC curve is 0.757. With the advancement of the treatment process, HCV RNA negative rate increased gradually, and fell back the end of 48 weeks of treatment. HCV RNA negative rate in patients whose baseline viral load less than 106 IU/mL was significantly higher than that of greater than 106 IU/mL at each time point.[Conclusion] HLA rs4273729 GG, IL28B rs12979860 CC, rs12980275AA and rs368234815 TT/TT genotyp was likely to associate with SVR of pegylated interferon and ribavirin treatment, baseline HCV-RNA, AFP, and GLU were also independent factors of SVR.