| Background and purpose: The affirmative response of antiviral therapyin chronic hepatitis B is HBeAg seroconversion or HBV-DNA negativeresult. Doctors and patients expect the ideal target of sustained response aftercessation of treatment,and the clearance of serum HBsAg or anti-HBstransformed. Now, in order to achieve a sustained response after cessation oftherapy, a majority of research indicates to prolong the treatment time ofnucleos (t) analogues, use of immunomodulatory agent after off-treatment.Is there any alternative way to reduce the nucleos(t)ide analogues course oftreatment,but also to achieve a sustained response after the drug withdrawal.In this study, the aim is to achieve a sustained response after drug withdrawaland limited dependency on telbivudine. This study is based on applyingtelbivudine in the treatment of HBeAg-positive chronic hepatitis B(CHB)after complete response then all of the patients are administeredTelebivudine for6months. according to patient’s willingness, differentoff-treatment methods were given i.e; either sequential IFN α-1b or single LDT consolidate treatment. The motto was to find the durability of sustainedresponse and to explore the value of serum HBsAg to forecast furtheranalysis on sustained response.Methods: we carefully monitored twenty HBeAg-positive chronichepatitis B patients who received telbivudine therapy in April2007toDecember2008at the Second Affiliated Hospital of Chongqing MedicalUniversity, Department of Infectious Diseases, getting complete responseless than52weeks. And then, after treatment with telbivudine for sixmonths,according to the patients wish,10patients were on oral telbivudinetreatment for6months,other10patients sequenced interferon α-1b(5millionunits/qod,subcutaneous injections, a total of6month). To analyze thetime of sustained response of each patient after treatment cessation thefollowing parameters were investigated such as liver biochemistry,HBV-M and HBV-DNA at1,2,3,6,12,18,24,30,36months respectivelyand to further explore the IFN drug untoward effects some basic check uplike Routine blood test and thyroid function tests were performed. LDTwithdrawal criteria is stated as follows: HBV-DNA negative, HBeAgserological conversion and the biochemical indicators are normal for morethan12months respectively, the general treatment duration≤100weeks.Relapse is defined as HBV-DNA level≥104copies/ml, or ALTlevel≥2UNL on the contrary unrelapse period is described on time durationover12months. HBV-DNA determination was made using the Roche MolecularSystems（PCR) with a lower limit of detection of500IU/mL. HBV serummarkers (HBsAg, HBsAb, HBeAg,HBeAb, HBcAb) detection by RocheCobas E601electrochemical luminescence analysis method. HBsAgquantitatively using MOUDULAR E170system detection, provided byRoche (Roche) pharmaceutical, the lower limit of detection of this assay is0.05IU/mL.Application of SPSS17.0statistical software for statistical analysis,the cumulative relapse calculation used Kaplan-Meier method. SerumHBsAg quantitative comparison between the two groups used T-test. Areaunder receiver operating characteristics (ROC) curves were used to assessthe performance of serum HBsAg at different time points during treatment topredict SR, and the differences between the areas under the ROC curveswere compared by DeLong test. With P <0.05represents statisticallysignificant.Results：(1) A total of13patients obtained sustained response in3years’ duration of follow up after treatment cessation.The overall sustainedresponse rate reached65%.The longest duration of maintaining effectivetreatment is forty months.7patients of the13obtaining sustained responserelapsed.the cumulative rate of relapse at3,6and12months after cessationof telbivudine was14.3%(n=1),42.9%(n=3),85.7%(6cases)respectively. The current disease recurrence happened on the34th month. The overall relapse rate of sequential IFN consolidate group is lower thanthat of single LDT consolidate group (30%vs40%, P>0.05);the differencewas not statistically significant. The cumulative relapse rate of two groupswere30%and65%(χ2=0.141, ν=1, Р=0.70);the difference was notstatistically significant.(2) Serum HBsAg tended to decrease duringtreatment. The reference range before and after telbivudine treatments were3.413±0.725log10IU/ml and2.957±0.688log10IU/ml (t=2.566, P<0.05);the difference was statistically significant.(3)Serum HBsAg of nonrelapsed group is gradually decreasing at12,24,48weeks on treatmentrespectively,whereas there is no marked decline in relapse group (4)Serum HBsAg levels decline On-treatment at week12,week24and week48could predict the relapse after treatment cessation,where as the differencebetween the baseline and on treatment was not statisticallysignificant.The areas under ROC curve at week24tend to be higher thanthose in week12and week48,but differences were not statisticallysignificant (P>0.05). The ROC curve area of week24is0.689, more thanweek12and week48(0.652vs0.545).(5) The patient of serum HBsAglevels at week24decreased≥1000IU/ml had a higher sustained responserate than the patients decreased <1000IU/ml [91.0%(10/11) vs33.3%(3/9), P<0.05], and the difference was statistically significant.(6) At the endof treatment, serum HBsAg levels <200IU/ml in patients had a lowerrelapse rate than the patients≥200IU/ml [0vs46.7%, P<0.05], the difference was statistically significant.(7)3patients got HBsAgseroconversion at cessation of telbivudine,and obtained clinical cure.Conclusion：(1)It can obtain the durability of the effects after cessationof telbivudine;(2) Sequential interferon alfa-1b consolidation therapy didnot reduce the rate of relapse after off-treatment.(3) At the treatment ofweek24, the sustained response rate of serum HBsAg levels decrease≥1000IU/ml in patients higher than others (P <0.05). |
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