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The Effect Of Peripheral Blood TGF-Beta On Hbeag Serological Conversion Of Chronic Hepatitis B Patients Treated With Nucleoside Analogues

Posted on:2016-03-25Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y MoFull Text:PDF
GTID:2284330461465490Subject:Infectious diseases
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Objective:To investigate the effect and the predictive value of peripheral blood TGF-β on HBeAg seroconversion of HBeAg-positive CHB patients with nucleoside analogue treatment.Methods:A total of 66 HBeAg-positive chronic hepatitis B patients were recruited. Fourteen of these patients were treated with LAM, four patients treated with ADV, fifteen patients treated with ETV, twenty five patients treated with LDT and eight patients treated with drug combination for at least 2 years and regular follow-up. Every month before the virological response and every three months after the virological response, HBVDNA, liver function and serum virus markers were respectively detected. Patients who meet the above standard and treat with nucleoside Analogues showing HBeAg serum conversion within 24 months were recruited in the Conversion group (34 cases). Patients who meet the above standard and treat with nucleoside Analogues showing no HBeAg serum conversion within 24 months was recruited in the Non-conversion group (32 cases). In addition, there were 32 normal people without liver disease in the Control group. Peripheral blood TGF-β in CHB groups baseline,3,6,12 months after the antiviral treatment and control group were detected by ELISA The TGF-beta level analysis was performed by SPSS 16.0. At the same time, the factors that may affect TGF-β levels before and after treatment were analyzed with the corresponding analysis. Repeated measures variance (ANOVA) process of the general linear model in SPSS was used in the comparison of TGF-βbetween HBeAg seroconversion within 2-year group, unconverted within 2-year group and among different treatment times. The diagnostic value of TGF- β in peripheral blood, before and 3,6,12 months after the antiviral treatment, was assessed by the calculation of the area under the receiver operating characteristic (ROC) curve (AUC).All cases in chronic hepatitis B group were divided into different groups according to the cut-off values, while the cumulative HBeAg serological conversion rates were compared with log-rank test among different subgroups.Results:(1)ALT levels of baseline data in transformation group were significantly higher than the un-transformation group (P< 0.05). Other indicators showed no significant difference among all groups. The cumulative HBeAg seroconversion rates of CHB patients treated in 12th and 24th months were 17.33%,48.60%, respectively.(2)The values of base line TGF-β in the CHB group were significantly higher than that of the control group (P<0.05). TGF-β in the HBeAg unconverted group were significantly higher than that of the HBeAg seroconversion group. TGF-β in the HBeAg seroconversion group were significantly higher than the control group(P<0.05).Repeated measures ANOVA analysis on the values of TGF-βshowed no significant difference was observed among baseline treatment status (initial/via treated), and different age groups (p>0.05). TGF-βin peripheral blood of male patients were significantly higher than that of the female patients (P=0.000).The results of partial correlation analysis showed that the baseline TGF-βin the HBeAg seroconversion and unconverted group were low positively correlated with HBV-DNA (lg) (r=0.228,p=0.02).while Baseline TGF-P, baseline HBeAg, baseline HBeAb, baseline ALT showed no significant correlation between the HBeAg seroconversion and unconverted group.(3)Bivariate partial correlation analysis showed that there were no significant correlations between TGF-p and HBeAg, HBeAb, ALT, HBV-DNA (lg) levels in the corresponding points in time after anti-viral treatment. The difference B TGF-P level in conversion group and unconverted group was statistically significant (p<0.001). The results of repeated measures analysis of variance test showed no significant difference in TGF-P levels among all drug group (TFG-β levels at baseline as a starting point)(P> 0.05). In the third month after antiviral therapy the differences between each drug group showed significant (p<0.05).(4) The TGF-P proportion under ROC curve of the third month is 0.897. Prediction of sensitivity and specificities of HBeAg seroconversion were 88.2%, 75%, respectively. The cut-off value was 0.6670. According to the cut-off values, cases were divided into different groups to take Log-rank test. And the result showed the rates of HBeAg seroconversion in the patients with TGF-β<0.6670 in the third months were significantly higher than patients with the base line TGF-β≥0.6670. (78.4%VS23.5%), p=0.000.Conclusions:(1) Peripheral Blood TGF-β in the CHB patients were sighnificantly higher than the normal. Peripheral Blood TGF-β in the HBeAg seroconversion group were si ghnificantly lower than the HBeAg unconverted group.In the process of CHB pa tients with antiviral nucleoside analogues treatment, TGF-β levels can inhibit H BeAg seroconversion.(2) After anti-viral therapy, TGF-β levels at different time can predict the probability of the occurrence of HBeAg seroconversion. The comprehensive efficiency of positive predictive value and negative predictive value of TGF-β levels in the third month is better. This can be used as one of the reliable indicators to predict HBeAg seroconversion in nuclear glycoside analogs antiviral treatment.
Keywords/Search Tags:nucleoside analogues, CHB, TGF-beta, HBeAg, seroconversion
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