| Objective1.To investigate the clinical efficacy,safety and virological breakthrough of Enticavir in the treatment of chronic hepatitis B and to explore the correlation between early virological response and long term curative effect.2.To investigate the influence of ETV on the suboptimal virological response in CHB patients.Methods1.Efficacy of entecavir in patients with chronic hepatitis B Select 162 cases of CHB patients treated with ETV from Department of Infectious Diseases,First Affiliated Hospital of Chengdu Medical College from January 2012 to December 2012.They were divided into initial treatment group and previously treated group.The HBe Ag status was divided into HBe Ag-positive group and HBe Ag-negative group in the initial treatment group.To evaluate the rates of ALT normalization,virological response,virological breakthrough,HBe Ag loss and serological conversion,HBs Ag < 100IU/ml at 12,24,48,144 and 240 weeks in different groups of ETV treatment.Based on whether HBV DNA was negative at 12 weeks,it was divided into early virologic response group and non-early virological response group in the initial treatment patients to evaluate the above indicators and further explore the correlation between early virological response and long-lasting response.At the same time,RT region sequencing analysis was performed on virological breakthrough patients who did not detect ETV genotype resistance.2.Analysis of related factors of suboptimal virological response to entecavir in patients with chronic hepatitis B.One hundred and fifty CHB patients who were diagnosed at the First Affiliated Hospital of Chengdu Medical College from January 2012 to December 2012 were divided into complete virologic response groups and suboptimal virologic response groups according to whether HBV DNA was negative at 24 weeks.The relationship between gender,age,baseline HBV DNA load,ALT level,HBe Ag status,presence or absence of cirrhosis,previous history of LAM treatment failure,and suboptimal response were analyzed.Results1.Efficacy of entecavir in patients with chronic hepatitis B1.1 Comparison of efficacy of ETV in CHB patients between initial treatment group and previously treated group There were 117 cases in the initial treatment group and 45 cases in the treatment group.There was no statistically significant difference in ALT normal rate,HBV DNA negative conversion rate and suboptimal virologic response rate at 12 weeks,24 weeks,48 weeks,144 weeks and 240 weeks in the CHB group and the previously treated group.But in 144 weeks and 240 weeks initial treatment group HBe Ag negative rate and serological conversion rate was higher than previously treated group,the difference was statistically significant(P < 0.05).The cumulative rate of virological breakthrough in the 240 weeks in initial treatment group was 5.12%,and previously treated group was15.56%.The cumulative rate of virological breakthrough in previously treated group was higher than that in initial treatment group,the difference was statistically significant.At144,192,and 240 weeks,the proportions of HBs Ag <100 IU/ml in initial treatment and previously treated groups were respectively 17.09%,17.95%,29.06%,and 8.89%,8.89%,and 8.89%,The difference between the initial treatment group and the previously treated group at 240 weeks was statistically significant.1.2 Comparison of the curative effect of HBe Ag positive group and HBe Ag negative group In this study,there were 55 cases of HBe Ag positive group and 62 cases in HBe Ag negative group.HBe Ag positive group and HBe Ag negative group in 12 weeks,24 weeks,48 weeks,144 weeks and 240 weeks when the rates of ALT normalization were 58.18%,85.45%,81.82%,87.27%,87.27% and 87.09%,87.09%,88.71%,90.32%,95.16%;the HBe Ag positive group at 12 weeks,the rates of ALT normalization was significantly lower than that of HBe Ag negative group,the difference was statistically significant(P <0.05).At 12 and 24 weeks,the negative conversion rate of HBV DNA in the HBe Ag negative group was better than that in the HBe Ag positive group,and the rate of suboptimal virological response was lower than that in the HBe Ag positive group(P <0.05).The cumulative rate of virological breakthrough in the 240 weeks was not statistically significant in the two groups.At 144,192,and 240 weeks,the proportion of HBs Ag <100 IU/ml in HBe Ag-positive and HBe Ag-negative groups was respectively10.91%,12.73%,21.82% and 22.58%,22.58%,35.48%;there was no statistical difference between the two groups at each time point of interception.1.3 Comparison of the effect of early virological response group and non early virological response group in the HBe Ag positive group.There were 37 cases of early virological response group and 17 cases in non-early virological response group.The rates of ALT normalization was not statistically significant in the two groups.At 24,48 and 144 weeks,the HBV DNA negative conversion rate in the early response group were better than those in the non-early virological response group(P < 0.05).The rates of HBe Ag loss and serological conversion at different time points in early virological response group were all higher than those in non-early virological response group,but there was no statistical significance at24 and 48 weeks.There was no statistical difference in the cumulative rate of virological breakthrough in the two groups.At 144 weeks,192 weeks and 240 weeks,the proportion of HBs Ag<100IU/ml in early virological response group and non-early virological response group was 10.53%,18.42%,28.95% and 11.76%,5.88% and 5.88%,respectively.1.4 HBV DNA reverse transcriptase region sequencing In this study,7 cases of virological breakthrough occurred and no entecavir genotype resistant serum were extracted for HBV DNA,nested PCR amplification,and cloned and sequenced.Among the 4 patients,entecavir genotype-resistance mutations were found in the sequencing results,and mutations in common ETV resistance gene loci were not found in 3 patients..The virological breakthrough after ETV treatment may be related to new locus mutations,such as rt H124 N.2.Analysis of related factors of suboptimal virological response to entecavir in patients with chronic hepatitis B.There were 115 cases of complete virologic response group and 35 cases in suboptimal virologic response group.There was statistically significant between the two groups in the previous history of LAM treatment failure,baseline ALT levels,HBV DNA load,and HBe Ag status.Multivariate regression analysis showed that baseline high levels of HBV DNA(OR=3.282,P=0.039),HBe Ag positive(OR=4.265,P=0.003),low ALT levels(OR=4.779,P=0.011),and previous history of LAM treatment failure(OR=2.890,P=0.040)were independent risk factors for suboptimal virological response.Conclusion1.ETV have good antiviral effect at the initial treatment and previously treated patients with CHB,ALT normalization rate and HBV DNA negative conversion rate during follow-up was no significant difference;but with the treatment time,144 weeks,240 weeks the initial treatment group HBe Ag loss rate and serological conversion rate was higher than the previously treated group(P < 0.05)and the previously treated group240 weeks cumulative virological breakthrough rate was higher than the initial treatment group.2.HBe Ag positive and HBe Ag negative CHB patients in the ETV treatment,the two groups of ALT normalization rate at 12 weeks,HBe Ag negative group was better than the HBe Ag positive group.At 12 and 24 weeks,HBV DNA negative conversion rate in the HBe Ag negative group was higher than that in the HBe Ag positive group.The rate of suboptimal virologic response in the HBe Ag positive group was higher than that in the HBe Ag negative group.3.After 144 weeks of ETV antiviral therapy,there were nearly 17% of the initial CHB patients who had reached the level of HBs Ag < 100IU/ml,and the proportion increased gradually with the time of treatment.The proportion of HBs Ag <100 IU/ml in the initial treatment group was significantly higher than that in the previously group at240 weeks.4.In ETV treatment of HBe Ag-positive initial treatment CHB patients,HBV DNA negative at 12 weeks had a good predictive effect on virological response within 144 weeks,but had no predictive effect on antiviral efficacy at 240 weeks.5.The virological breakthrough after ETV treatment may be related to new locus mutations,such as rt H124 N.6.Baseline high HBV DNA load,HBe Ag positive,low ALT levels,and previous history of LAM treatment failure were independent risk factors for suboptimal virological response in CHB patients after ETV antiviral therapy. |
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