Study Of The Association Of Interleukin-28B Gene Polymorphism With Prognosis Of Diseases And Response To Antiviral Treatment With PEG-IFNα-2a In Hepatitis C Virus/Hepatitis B Virus Infected Patients

Part1Study of the association of interleukin-28B gene polymorphism withprognosis of disease and response to antiviral treatment withPEG-IFNα-2a in hepatitis C virus infected patientsAims：To analyze the association of interleukin-28B gene polymorphism with prognosisof disease and response to antiviral treatment with PEG-IFNα-2a and RBV in hepatitis Cvirus (HCV) Infected patients.Methods：The candidate polymorphism rs12979860of IL28B gene was genotyped bymeans of polymorphism chain reaction (PCR) amplification and direct PCR sequencing, andthen the relationship between this single nucleotide polymorphism (SNP) and prognosis ofdisease and treatment response with PEG-IFNα-2a and RBV in335patients with HCVchronic infection was analyzed. For comparison,277healthy individuals were included.Results：There was no statistical difference was found in allelic and genotypicfrequencies of rs12979860among healthy individuals、chronic hepatitis C patients andHCV-related cirrhosis patients (P>0.05, respectively). Compared with the HCV infectedpatients carrying rs12979860CC genotype, those patients carrying non-CC genotype had asignificantly higher average HCVRNA concentration at baseline (5.33lg copies/ml versus4.77lg copies/ml, P<0.05). In the chronic HCV infected patients who obtained a RVR orSVR, a significantly higher proportion of the rs12979860CC genotype carries was foundthan that of non-CC genotype carriers (P<0.05, respectively). As for genotype1HCVinfected patients, in those who obtained a RVR or SVR, the rs12979860CC genotype carrieshad a respectably higher proportion in comparison with non-CC genotype carries (P<0.05,respectively). Moreover, for patients who failed to achieved an RVR, Compared withnon-CC genotype, rs12979860CC genotype carriers had a significantly higher rate of SVR(38.8%), P<0.05. While for non-genotype1HCV infected patients, a highly significant association was only found between the rs12979860CC genotype and RVR (P<0.05), butnot SVR and SVR regardless of RVR achievement. The CC genotype of rs12979860wassignificantly correlated to the SVR in chronic HCV infected patients with both groups ofhigh baseline viral load or low baseline viral load. But no significant difference was foundbetween the two groups (P>0.05). The similar result was also found in chronic HCV infectedpatients with different disease states groups. The average decrease of Knodellnecroinflammatory scores in the HCV infected patients carrying rs12979860CC genotypewas2.3points, significantly higher than that of those patients carrying non-CC genotype(1.2), P<0.05. The average decrease of Ishak fibrosis scores in the HCV infected patientscarrying rs12979860CC genotype was1.4points, significantly higher than that of thosepatients carrying non-CC genotype (0.7), P<0.05. Multivariate logistic analysis (odds ratio;95%confidence interval; P value) indicated that the rs12979860CC genotype (7.32;3.68-16.72;<0.001) was one of the independent predictors for SVR to antiviral treatment ofpatients with HCV chronic infection. The main adverse reactions of the antiviral treatmentwith PEG-IFNα-2a and RBV displayed a similar frequency in HCV infected patientscarrying rs12979860CC and non-CC genotypes (P>0.05, respectively).Conclusions: In the North of Chinese Han population, IL28B rs12979860polymorphism had no association with prognosis of disease in patients with HCV infection.However, IL28B rs12979860polymorphism was significantly associated not only withaverage HCVRNA concentration at baseline, but also with respone to antiviral treatment ofchronic HCV infected patients, especially in HCV genotype1infected patients. Combineassessment of HCV genotype and the IL28B polymorphism maybe beneficial for theindividualize treatment decision making in Asian chronic HCV infected patients. Part2Study of the association of interleukin-28B gene polymorphism withprognosis of disease and response to antiviral treatment withPEG-IFNα-2a in hepatitis B virus infected patientsAims：To analyze the association of interleukin-28B gene polymorphism with prognosisof disease and response to antiviral treatment with PEG-IFNα-2a in hepatitis B virus (HBV)infected patients.Methods：The candidate polymorphism rs12979860of IL28B gene was genotyped bymeans of polymorphism chain reaction (PCR) amplification and direct PCR sequencing, andthen the relationship between this single nucleotide polymorphism (SNP) and prognosis ofdisease and treatment response with PEG-IFNα-2a in389patients with chronic HBVinfection was analyzed. For comparison,277healthy individuals were included.Results：There was no statistical difference was found in allelic and genotypicfrequencies of rs12979860among healthy individuals、chronic hepatitis B patients andHBV-related cirrhosis patients (P>0.05, respectively). Compared with the HBV infectedpatients carrying rs12979860CC genotype, those patients carrying non-CC genotype had asignificantly higher average HBVDNA concentration at baseline (5.58lg copies/ml versus5.16lg copies/ml, P<0.05). In the chronic HBV infected patients who obtained a EVR, asimilar proportion was found between the rs12979860CC and non-CC genotype carries(P>0.05). While in the patients with a SVR, rs12979860CC genotype carries had asignificantly higher proportion than that of non-CC genotype carriers (70.4%versus29.1%,P<0.05). And among the patients who failed to achieve an EVR but extend the treatment to72-week, compared with non-CC genotype, rs12979860CC genotype carriers had asignificantly higher proportion for getting a SVR (86.5%versus20.7%, P<0.05). Furthermultivariate logistic analysis (odds ratio;95%confidence interval; P value) showed that thers12979860CC genotype (3.14,1.77-5.53,0.001) was one of the independent predictors forSVR to antiviral treatment with PEG-IFNα-2a in HBV infected patients. As for patients withHBeAg-negative HBV infections, in those who obtained a SVR, the rs12979860CCgenotype carries had a respectably higher proportion in comparison with non-CC genotype carries (72.2%versus32.3%, P<0.05). Moreover, for patients who failed to achieve an EVRbut extend the treatment to72-week, compared with non-CC genotype, rs12979860CCgenotype also had a significantly higher proportion for obtaining a SVR (90%versus31.3%,P<0.05). Further multivariate analysis revealed that the rs12979860CC genotype (4.41;1.06-13.3;0.001) was one of the independent predictors for SVR to antiviral treatment withPEG-IFNα-2a in HBeAg-negative HBV infected patients. While for patients withHBeAg-positive HBV infection, in those who obtained a SVR or HBeAg serum conversion,rs12979860CC genotype carriers had a significantly higher proportion in comparison withnon-CC genotype carriers (P<0.05, respectively). Furthermore, for patients who failed toachieve an EVR but extend the treatment to72-week, Compared with non-CC genotype, CCgenotype carries also had a significantly higher proportion for getting a SVR or HBeAgserum conversion (P<0.05, respectively). Further multivariate logistic analysis indicated thatthe rs12979860CC genotype was one of the independent predictors for not only SVR (1.99,1.31-2.75,0.013) but also HBeAg serum conversion (3.43,1.54-7.71,0.011) to antiviraltreatment with PEG-IFNα-2a in HBeAg-positive HBV infected patients. The averagedecrease of Knodell necroinflammatory scores in the HBV infected patients carryingrs12979860CC genotype was2.4points, significantly higher than that of those patientscarrying non-CC genotype (1.1), P<0.05. The average decrease of Ishak fibrosis scores in theHBV infected patients carrying rs12979860CC genotype was1.5points, significantly higherthan that of those patients carrying non-CC genotype (0.6), P<0.05. The main side effects ofthe antiviral treatment with PEG-IFNα-2a displayed a similar frequency in HBV infectedpatients carrying rs12979860CC and non-CC genotypes (P>0.05, respectively).Conclusions: In the North of Chinese Han population, IL28B rs12979860polymorphism had no association with prognosis of disease in patients with HBV infection.IL28B rs12979860polymorphism was correlated not only to HBVDNA concentration atbaseline, but also to response to antiviral treatment with PEG-IFNα-2a in chronic HBVinfected patients, especially significantly correlated to SVR and HBeAg serum conversion inthose failed to achieve an EVR but extend the treatment to72-week patients. Therefore,Combine assessment of EVR and the IL28B polymorphism may be beneficial for the individualize treatment decision making in chronic HBV infected patients. That is, forpatients regardless HBeAg states who failed to achieve an EVR to antiviral treatment withPEG-IFNα-2a, to extend the period of treatment can be used in those carrying rs12979860CC genotype patients, which may be contribute to the best therapeutic effects.