The Relationship Between The Expression Of Toll Like Receptor 9signal Pathway And Hepatitis B Virus Reactivation In HBV Related Hepatocellular Carcinoma With HBV-DN Negative After TACE

Part Ⅰ HBV reactivation rate and risk factors of HBV-DNA negative HBV related HCC patients after TACE treatmentObjectiveTo clarify the hepatitis B virus(HBV)reactivation rate and clinical risk factors of HBV-DNA negative HBV related hepatocellular carcinoma(HCC)patients after transcatheter arterial chemoembolization(TACE)treatmentMethodsPatients with HBV-DNA negative HBV related HCC were randomly divided into treatment group and control group;(1)treatment group(n=30):patients received regular Enteeavir antiviral treatment before and during TACE;(2)control group(n=29):patients did not receive antiviral treatment during TACE treatment.The reactivation rate of HBV,liver function and intrahepatic lesions were evaluated in two groups after TACE-The reactivation rate of HBV,clinical risk factors,liver function and tumor control rate were analyzed.ResultsFour weeks after TACE,a total of 10 patients developed HBV reactivation,of which 9 occurred one week after TACE and 1 occurred 2 weeks after TACE.HBV reactivation was found in 8 cases(27.59%)in the control group,and in 2 cases(6.25%)in the treatment group.The difference of HBV reactivation rate between the two groups was statistically significant(P<0.05).There was no significant difference in objective response rate(RR)and disease control rate(DCR)between the two groups 4 weeks after TACE treatment.The level of transaminase in HBV reactivated group was significantly higher than that in no HBV reactivated group(P<0.05).The HBeAg positive,the number of intrahepatic tumors>3,and no antiviral treatment were the clinical risk factors for HBV reactivation.ConclusionHBV reactivation can be induced in patients with HBV-DNA negative HBV related HCC during TACE treatment.Positive HBeAg.more than three intrahepatic tumors and no antiviral treatment are the clinical risk factors for HBV reactivation after TACE treatment.TACE combined with Entecavir for prophylactic antiviral treatment can reduce the reactivation rate of HBV and protect the liver function of patients.Part Ⅱ Molecular expression level and cytokine secretion in TLR9 signaling pathway and HBV reactivationObjectiveTo investigate the relationship between Hepatitis B virus(HBV)reactivation and Toll like receptors 9(TLR9)signaling molecule mRNA expression and cytokine secretion in HBV-DNA negative patients with HBV related hepatocellular carcinoma(HCC)after transcatheter arterial chemoembolization(TACE)treatment.MethodsPlasma-like dendritic cells were isolated from peripheral blood of HBV-DNA negative patients with HBV related HCC before and 1 week after TACE.The expression of TLR9 signaling pathway molecules(TLR9,MyD88,TRAF6,IRF7)mRNA was quantitatively detected,and the levels of cytokines(IFN-α,IL-8,IL-12,TNF-α)in plasma were detected.The differences in expression of cytokines and cytokines before and after operation were compared.ResultsHBV reactivation occurred in 9 patients after 1 weeks of TACE treatment.The expression levels of TLR9 signaling pathway molecule(TLR9,MyD88,TRAF6,IRF7)mRNA in HBV reactivated group were lower than those in no reactivated group before and one week after TACE treatment.The expression levels of TLR9,MyD88 and IRF7 mRNA in HBV reactivated group and no reactivated group were significantly different(P<0.05).The secretion of IL-8,IL-12,IFN-α and TNF-α in HBV reactivated group was lower than that in no HBV reactivated group before and after treatment,and the decrease of IFN-a was statistically significant(P<0.05).There was no significant difference in TLR9 signaling pathway mRNA and cytokines between the treatment group and the control group before and after TACE treatment.ConclusionThe transcriptional levels of TLR9,MyD88,IRF7 and the secretion of IFN-a in HBV-DNA negative patients with HBV related HCC reactivated after TACE were significantly lower than those in no reactivated patients.We speculate that abnormal TLR9 signaling pathway and low IFN-a levels in peripheral blood play an important role in HBV reactivation.HBV reactivation in patients after TACE may be due to the dysfunction of TLR9-MyD88-IRF7-IFN-a signaling pathway.Entecavir did not reduce the reactivation rate of HBV by acting on the TLR9 signaling pathway.Patients with decreased IFN-a should be received antiviral treatment before TACE treatment.