Study On Plasma Cytokines Which Predict The Therapeutic Efficacy Of Pegylated Interferon In Patients With Chronic Hepatitis B

Objective:Chronic hepatitis B(CHB)is a chronic immune-mediated infectious disease caused by hepatitis B virus(HBV).Recently,the treatment of CHB is mainly antiviral.These days,interferon-? has become a clinical first-line treatment for CHB,but only one-third of patients have a good prognosis.No indicator that can be applied clinically to predict the prognosis of IFN-? therapy has been found.In recent years,some scholars have found that the change of cytokine storm may be closely related to the disease progression in CHB patients.However,the timing,intensity,duration of the cytokine storm in CHB patients and the recombination relationship in the cytokine network have not yet been fully understood.Therefore,we aimed to clarify whether there is a significant correlation between the change of cytokine storm and the virological response of HBeAg-positive patients after IFN-? therapy in patients with CHB,so that we can predict the effect of IFN-? therapy in the early stage.Methods:We recruited 19 HBeAg-positive patients who were initially treated with pegylated interferon(Peg-IFN)and followed up for 24 weeks.Patients were divided into virologic partial response group(HBV DAN decreased significantly after 24 weeks of treatment with more than 2 log10 IU/ml)and no response group(HBV DNA decline less than 2 log10 IU/ml after 24 weeks of treatment)according to the level of HBV DNA decline after 24 weeks of treatment.At the same time,19 healthy adults were recruited as healthy controls.The levels of 27 cytokines in 19 healthy controls and 19 CHB patients followed up for 0,4,8,12 and 24 weeks were measured and statistically analyzed.Results: 1.Inflammatory factor IL-1?,adaptive factor IL-5,and chemokine MIP-1? were significantly different between the virological partial response group and the healthy control at baseline level,while the no response group and the healthy control at the baseline level have no significant difference.Therefore,these cytokines may relate to the therapeutic efficacy of IFN-? before treatment.2.There was a significant difference in the correlation between cytokines at baseline,with 186 statistically significant associations(57.2%)between the individual cytokine levels in the virologic partial response group.In contrast,only 79(24.3%)had such a correlation(p <0.05)in the virologic no response group.Thus,the network of cytokines in the virologic partial response group became more interlocked than the network in the virologic no response group,which indicate that the highly coordinated immune system is closely related to disease prognosis.In addition,there are negative correlations between RANTES,IP-10,MCP-1 and other cytokines in the virological no response and may also be related to disease progression.3.During the disease progression,cytokine levels tended to decrease after treatment with Peg-IFN.Compare to the virological no response group,growth Factor VEGF,FGF basic,PDGF-bb,hematopoietic Factor IL-7,G-CSF,inflammatory Factor IL-12,chemokine MIP-1?,anti-Inflammatory Factor IL-7 in virologic partial response group were decreased after 12 weeks Peg-IFN therapy with statistical significance.The downtrend of the virological no response group was not obvious,without statistical difference.4.Chemokine MIP-1? in the treatment of 4-12 weeks,has a statistically significant difference(P = 0.005)between the virological partial response group and the no response group,the difference between the 12 th week of treatment is the most significant.Simultaneous application of ROC curves and survival curves confirmed that MIP-1? was found to be more susceptible to virological partial response in patients with low expression after 12 weeks of treatment.Hence,this factor may be used to predict the therapeutic effect of IFN-?.Conclusion:Study on cytokine storms in patients with HBV infection and antiviral therapy indicate that plasma levels of cytokines in HBV patients are higher than those in healthy controls,and cytokines in the partial response group after IFN-? treatment are significantly decreased.In the partial response group,the increase of baseline cytokines was observed.After 12 weeks of treatment,the level of MIP-1? in the virological no response group was significantly higher than that in the partial response group,which could predict poor prognosis.