| BackgroundChina is an area where chronic hepatitis B occurs frequently, and the population of the patients have reached about 20,000,000 and approximately 100,000 people died every year because of the relevant disease of serum hepatitis B. The treatment goal for the chronic hepatitis B patients is to improve the liver inflammation, to inhibit the liver fibrosis, for the purpose of preventing the condition progresses to the liver cirrhosis,fibrosis and function failure. The anti-virus treatment is a key.Peginterferon Alfa-2a is the first line drug for anti-virus treatment of chronic hepatitis B. It not only takes an action in the process of gene duplication, the expression and so on, but also can regulate the immunologic function of host, forming anti-virus activity of which makes a good treatment for chronic hepatitis B . The clinical trial of peginterferonα-2a III phase showed that after 48 week treatment course by using peginterferonα-2a only, the HBeAg transfering ratio of the HBeAg positive hepatitis B patients obtained was 32%. Clearance rate of Serum hepatitis B surface antigen was 8% after three years follow-up.Although the effect was good, regarding to the great individual differences of HBeAg positive chronic hepatitis B patient, only a part of patients may obtain response completely. Therefore, it is necessary to find predictors to solved questions about how to give out the individuation treatment and avoids the unnecessary side-effects.The ideal predictors should be able to reflect the suppression degree of the viral and the control degree of the immune status simultaneously. The past studies focused on sex, age, the medical history, hepatic pathology ,single gene polymorphisms, the ALT, HBV DNA viral load , Hepatitis B Virus Genotype, HBVDNA viral load and so on, as predictors in the past. But we are lack of dynamics in the course of Treatment. There are some clinical problems which can't be solved. Recently some studies reported that HBeAg serum levels could predict virological response. There were two predictors including low HBeAg serum levels of pre-treatment and rapid declining in the first 8 weeks during the treatment.Over 97% of cases were Genotype B and Genotype C in China. The effect of peginterferonα-2a was lower than The United States and Europe. We are still lack of prospective cohort study about HBeAg serum levels and HBVDNA viral load in the course of treatment.This study is a prospective cohort study to evaluate the value of HBeAg quantitative values, HBVDNA viral load for predicting HBeAg seroconversion in patients treated with peginterferonα-2a . Therefore, we should supply individualized treatment for HBeAg positive hepatitis B patients.Objective1. To detect HBeAg quantitation and HBVDNA viral load dynamically in HBeAg positive chronic hepatitis B patients treated with peginterferonα-2a before and during treatment. To observe the relationship between decline mode and viral response at the 48th weeks of teeatment.2. To evaluate the predictive value of HBeAg quantitation and HBVDNA viral load for HBeAg positive CHB patients treated with peginterferonα-2a which provides reference information for individualized anti-virus treatment of different CHB patients.Objects And MethodsResearch Object: To select the 69 patients who were diagnosed according to CHB diagnosis standard set by the 12th National Conference on HBV in 2005. They had HBsAg positive and history more than half a year. HBeAg positive, HBVDNA> 10^4IU/ml.And the possibility of being infected with other hepatitis virus(HCV/HDV/HAV/HEV) had been excluded . Also, the possibility of being suffered from thyroid disease, mental disease, autoimmune disease, malignant tumor had been excluded. Moreover, they have not accepted any anti-viral treatment or the immunity adjustment treatment six- months before therapy.Method1. Treatment: The patients administered peginterferonα-2 by subcutaneous injection, once a week and 180ug for each time, treatment course was 48 weeks. the treatment should be terminated if the serious adverse events occurred.2. Testing methods(1) HBV DNA : The fluorescence quota polymerase chain reaction law (FQ-PCR), determined by the fluorescence quota PCR examination system belonging to DaAn Gene company of Guangzhou, China.(2) HBeAg value: HBeAg ,anti-HBe value determined by diagnostic kits of HBeAg ,anti-HBe, belonging to German Roche Corporation. The inspection adopts chemo luminescence method.(3)Serum ALT, AST: determine by CL-8000 completely automatic biochemistry analyzer belonging to SHIMADZU Corporation examination.(4) Thyroid function tests: determined by diagnostic kits of T3,T4,TSH ,belonging to German Roche Corporation. The inspection adopts chemo luminescence method.3.The examination of items (2),(3),(4) above mentioned were measured at baseline,week12,week24,week36,week48.4. Virology response(1)Complete response (CR): The HBeAg/HBeAb seroconversion, HBV DNA viral load<1×10E3 IU/ml, ALT, AST were normal or≤1.5 times of normal value upper limit.(2) partial response (PR): ALT,AST were normal or≤1.5 times of normal value upper limit, HBV DNA <10E3 IU/ml, but without HBeAg/HBeAb seroconversion.(3) No response: Had not achieved above response.(4) Early stage response: the response within 12 week's treatment.Results1.In 69 patients, when treated for 12 weeks, 7 cases(10.1%) achieved the early complete response, 8 cases (11.6%) achieved partial response. When treated for 24 weeks: 14 cases (20.3%) achieved the complete response, 22 cases (31.9%) achieved the partial respondse. When treat for 48 week: 24 examples (34.8%) achieved the complete responder, 29 cases (42.0%) achieved partial response.3 cases achieved HBsAg transfers to negative (4.3%) when treated for 48 weeks2. There is no correlation between viral complete response at 48weeks and ALT(P=0.89), HBeAg quantitation (P=0.73),HBVDNA viral load(P=0.23)at baseline.3. Relationship between the decline degree of HBVDNA viral load and complete response.(1)There were significant differences between complete response group and non-complete response group in deline degree of HBVDNA viral load at 12,36,48 weeks.(2) It is significant correlation with HBVDNA<10E5IU/ml at week 12(P=0.003) and week24(P<0.0001).(3)The patients whose HBVDNA viral loads declined rapidly before 12 weeks and decline degree was more than 4logIU/ml had high complete response. The velocity of decline slowed after 24 weeks.4. Relationship between HBeAg value and complete response:(1)There are no correlation with HBeAg value at baseline(P=0.44).It is significant correlation with HBeAg <54.84 at week12(P=002) (OR 5.38,95%CI 1.82～15.88)。(2)It is significant correlation with HBeAg <11.38 at week24 (OR 10.45,95%CI3.19～34.22)。(3) The patients whose HBeAg quantatition declined rapidly before 12 weeks and decline degree was more than 90% had high complete response. The velocity of decline slowed after 24 weeks.6. ROC curve predicting complete response : HBeAg value at week12(AUC=0.819,P<0.001),HBVDNA load at week 12(AUC=0.768,P<0.001), HBVDNA load at week24 ( AUC=606,P=0.149 ), HBeAg value at week 24(AUC=0.734,P=0.001)。HBeAg is a better predictor of complete response than HBVDNA.Conclusions1. Dynamic HBVDNA viral load and HBeAg quantitation could be valuable predictor during the course of Peginterferonα-2a in HBeAg positive CHB patients. The rapid decline of HBeAg quantitation and HBVDNA viral load at 12 weeks of treatment had highly predictive value for complete response in CHB patients treated with Peginterferonα-2a.2. The difference of the HBeAg value and HBVDNA viral load were significantly between complete response group and uncomplete response group.
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