The Significance Of ISG15/USP18 In Predicting Response To Interferon Therapy For Chronic Hepatitis B

Objective: Interferon is one of effective treatment for chronic hepatitis B(CHB),which has low cure rates,and is lack of correct prediction of treatment response.The ISG15/USP18 is a pair of IFN stimulated genes, ISG15 has antiviral fuction to specific virus,USP18 can inhibit the effect of interferon for anti-HCV, but what role of ISG15/USP18 in IFN anti-HBV is unknown untill now, so this reasarch tries to explore the fuction of ISG15/USP18 during the treatment for CHB with IFN,and to determine the significance of ISG15/USP18 in predicting responses to IFN therapy in patients with chornic hepatitis B.Methods: 30 healthy persons with non-viral liver disease were analyzed as control group.In experiment set 30 patients chronically infected with HBV were treated with IFN-a for 24 weeks,mRNA expression levels of ISG15/USP18 in their peripheral blood mononuclear cells(PBMCs) were measured using RT-PCR before and during therapy(1 week,12 weeks,24 weeks).PEMS 3.1 medical statistic software was used to analyzed the difference of ISG15/USP18 positive expression rate between reponders (Rs)and non-responders(NRs).The included criteria,diagnosis and treatment response in the experiment set were accord to the guideline for chronic hepatits B of China which was published in 2005.Results: No expression of ISG15/USP18 was detected in control group and the 30 patients before therapy initiated. Final outcome of the 30 patients was as follows :16 were R defined as decrease in serum HBV-DNA to undetectable levels by PCR assays, and loss of HBeAg in patients who were initially HBeAg positive, normalization of liver fuctuion;14 were NR defined as decrease in serum HBV-DNA by <2 log10 IU/ml after 24 weeks of therapy.The positive rate of ISG15 expression in R and NR was 50.0%,57.1%, respectively, P=0.696>0.05, which made no significantly difference.The positive rate of USP18 expression in Rs and NRs was 50.0%,92.8%,respectively,P=0.017<0.05,which made significantly difference. For the patients with USP18 positive expression between the Rs and NRs,the ALT level,HBV-DNA virus load and the HBeAg positive rate before the initial of the therapy were analyzed comparbaly,the P value were 0.096,0.346,0.056, respectively,all of the them were higher than 0.05,which made no significantly difference.The ISG15/USP18 expression results of each patient at 12th and 24th weeks during therapy were same with the results at 1st week of therapy.Conclusions: No expression of ISG15/USP18 was detected in control group and the 30 patients before therapy initiated.The ISG15 positive expression in R and NR had no significantly difference.As an independent facotr,ISG15 can not be used to predict the effect of IFN .The USP18 positive rate in NR was significantly higher compared with R, USP18 itself maybe independently useful to predict the nonresponse to therapy. The ALT level,HBV-DNA virus load and the HBeAg positive rate before the initial of the therapy had no effect on the induction of USP18 and its predictive power to IFN.