Study On The Clinical Significance Of Interferon Stimulated Gene USP18 And OAS2 To Predict The Outcome Of CHB Cured With Interferon

Hepatitis B Virus(HBV)infection at present is still one of the most serious public health problem worldwide.China is a highly prevalent area of Hepatitis B Virus infection.IFN alpha(IFNa)treatment inhibit viral replication directly and regulate the patients’ immune response,which make IFN alpha treatment has higher HBsAg clearance to achieve a complete cure.The response rates of IFNα treatment is significant different between individuals.The overall sustained response rate of IFNα treatment is relatively low,and easy to produce inevitable severe side effects in the process of treatment,in order to reduce unnecessary economic burden,effective prediction of IFNa treatment is extremely necessary before the treatment.In the first part of this study,we expanded the clinical specimens of cohort and continuous follow-up study to focus on the research at the early stage,which found that the two ISGs(USP18,OAS2)have a significant expression difference between the responders and non-responders.We found that patients treated with IFNa at week 24,the relative level of USP18(IFNα-N)mRNA is significant higher in VR(-)group than that in VR(+)group.When patients were regrouped according the outcome of IFNa therapy at week 48,the level of USP18(IFNα-N)mRNA in VR(-)group is still significantly higher than that in VR(+).When we further classified the patients into SOTVR(+)or SOTVR(-),and SR(+)or SR(-),the USP18(IFNa-N)mRNA level is also significantly higher in non-response group than that in response group.The relative level of OAS2(IFNα-N)mRNA only has significantly diifference between VR(+)and VR(-)at week 24.The performance of USP18(IFNα-M mRNA and OAS2(IFNα-N)mRNA to predict IFNa treatment outcome was analyzed using ROC analysis.The multivariate regression analysis showed that USP18(IFNα-N)mRNA level was a strong independent predictor for IFNa treatment outcome.The high USP18(IFNα-N)mRNA level was significantly associated with patient as VR(-)at week 24,as VR(-)at week 48,as SOTVR(-)and SR(-).In the second part we established a high sensitivity real-time RT-qPCR system of USP18,which provides an effective method for the rapid and stable detection of USP18mRNA.The third part we established the IFNa stimulation system of whole blood specimen of patients before IFNa treatment and effectively extracted mRNA of whole blood specimen and detected the USP18 mRNA expression level of 24 patients to explore the clinical significance of USP18 mRNA expression level to predict the outcome of IFNa treatment of patients.In conclusion,this paper initially illustrated the clinical significance of USP18,OAS2 in patients before IFNa treatment to predict the outcome.We established the real time RT-qPCR detection system of USP18 with high sensitivity and detected relative mRNA expression level of USP18 in whole blood of 24 patients.The next step we will continue to carry out the cohort study of multi-clinical centers,and further analyze the predictive value of USP18.At the same time,the correlation between the genetic background of patients and the treatment response of IFNa will be investigated.To provide effective guidance for the treatment of IFNa in patients with chronic hepatitis B.