The Effects Of HBV Precore W28STOP Mutation With The Early Response Of Interferon Therapy On Patients With HBeAg Positive Chronic Hepatitis B

Objective:To investigate the influence of hepatitis B virus (HBV) pr ecore W28STOP mutation and HBV genotypes in case of interferon-alph a (IFN-a) treatment to HBeAg positive chronic hepatitis B (CHB).Methods:193CHB patients with HBeAg positive were treated with IFN continuously for12weeks to24weeks by the principle of voluntary. The patients were asked to be reexamined regularly, and their serums wer e collected at baseline,12and24weeks after treatment, and12weeks after cessation of treatment to observe HBsAg, HBeAg, anti-HBe, HBV DNA, HBV and mutation status of precore gene W28STOP, etc. Effects of treatment for12weeks and24weeks, and12weeks after withdrawal, as well as the influence of early response at12weeks to the effect of treatment for24weeks and after withdrawal for12weeks were all analyzed. At the same time, the influence of HBV genotypes and precore W28STOP mutation to the effects of treatment for12and24weeks, and12weeks after withdrawal as well were analyzed also. All related data were analyzed and contrasted by statistical method. Results:1. Treatment effect:(1)Early response:37.82%(73/193) of the patients obtained early virologic response. HBsAg titer of75.12%(145/193) of the patients decreased, and HBeAg titer decreased≥0.51og10compared with the baseline in46.63%(90/193) of the patients. HBsAg titer of34.20%(66/193) of the patients decreased while their HBV DNA level decreased≥21og10compared with the baseline.(2) Response to treatment for24weeks:9.92%(12/121) of the patients obtained complete response, and17.36%(21/121) obtained partial response.(3) Response to treatment for24weeks and withdraw for12weeks(SVR12):HBeAg of30.77%(24/78)≤10S/CO with or without anti-HBe<1S/CO. Among them HBV DNA level of33.33%(8/24)<103IU/ml, which means they have obtained complete response. And HBV DNA level of66.67%(16/24)>103IU/ml, which means they have obtained partial response.(4) the relationship of early response with the response of treatment for24weeks, withdraw for12weeks:①The patients with early HBsAg response got a better response at24weeks after treatment (x2=7.673, P=0.022); there are same tendency at withdrawal for12weeks, however, there is no statistically significant(x2=3.511, P=0.173).②The patients with early HBeAg response obtained a better response at24weeks after treatment (x2=31.843, P=0.000), and gained a better response at withdrawal for12weeks(x2=26.379, P=0.000).③The patients with HBsAg titer decreasing and HBV DNA level decreasing≥21og10after treating for12weeks had better therapy effects by using interferon for24weeks (x2=26.379, P=0.000). The difference between the therapy effects of withdraw for12weeks and treatment for24weeks are not significant (x2=5.804, P=0.055)2. The effect from the HBV precore W28STOP mutation(1) The patients with the mutation of W28STOP in HBV precore region at baseline were significantly associated with the early virological response(x2=15.684, P=0.000), the early HBeAg response (x2=17.267, P=0.000), and the response of HBsAg and of HBV DNA over21og10(x1=18.624, P=0.000). Moreover, those patients,whose mutation were changed from existence at baseline to not at12weeks after treatment, would get best response.(2) The patients with the mutation of W28STOP at12weeks after therapy were more proned to poor early HBsAg response (x2=6.300, P=0.012)(3) The patients with the W28STOP mutation both at baseline and treatment for12weeks were significantly associated with the virological and serological combined response at24week (x2=8.484, P=0.007) (4) The patients with the W28STOP mutation at12weeks after treatment were more likely to achieve the complete response (x2=4.993, P=0.039).3. The effect from the HBV genotypes:There is no association between HBV genotype B and genotype C and the efficacy of IFN treatment in our reseach.Conclusion:1. In our reseach, there are75.12%of patients got the early HBsAg response,46.63%obtained early HBeAg response, and34.2%gained the early response of HBsAg combined with HBV DNA after12weeks’treatment. There are9.92%and17.36%of patients received complete and partial response respectively after24weeks’treatment. The efficacy after drug withdrawal for12weeks is stable.2. We can predict the treatment efficacy at24weeks after treatment and12weeks after drug withdrawal by early response. The early response of declining the quantity HBsAg and HBV DNA over21og10was the best positive predictor; however, there are no differences to choose the negaitve predictor in HBsAg, HBeAg, HBsAg combined with HBV DNA at12weeks after treatment.3. The patients with the mutation of W28STOP in HBV pre-core region at baseline, especially the patients with declined mutation ratio at12weeks after treatment, were significantly associated with better response therapy with interferon. It means that the existence of W28STOP and its change at the early step treatment can be a value predictor.