Clinical Study On The Relationship Between Expression Patterns Of HBcAg In Hepatocytes And Response To Interferon-alpha In HBeAg-postive Chronic Hepatitis B

Objective:(1) To observe the relationship between expression patterns of HBcAg in liver tissue of Chronic Hepatitis B with the inflammation activity in liver tissue and efficacy of interferon-alpha by clinical cases.(2) To investigate the best timing of antiviral therapy and to improve the response rate of IFN-a therapy.Methods:216 cases of patients with HBeAg-postive chronic hepatitis B from Hepatopathy Department in Xiamen Traditional Chinese Medicine Hospital affiliated to Fujian College of Traditional Chinese Medicine during February,2006 to September,2007 were conducted liver biopsy,determined expression patterns of HBcAg in liver tissue by immunohistochemistry staining method,classified into four groups:nuclear localiazation of HBcAg group,cytoplasmic localiazation of HBcAg group,nuclear localiazation of HBcAg dominant group and cytoplasmic localiazation of HBcAg dominant group.All the patients were treated with 5MU IFN-a subcutaneously thrice a week for 6 months.To observe and detect between pre and post treatment:(1) serum alanine transaminase(ALT), serum aspartate aminotransferase(AST);(2) serum HBVM(Electrocherniluminescence kit);(3)serum HBVDNA(fluorescence quantitative PCR);(4) predict the outcome of treatment.Statistical methods:x~2 test,logistic regression analysis,and so on.Results:(1)The 216 cases of patients accorded with the inclusive criteria were classified into nuclear localiazation of HBcAg group(35),cytoplasmic localiazation of HBcAg group(58),nuclear localiazation of HBcAg dominant group(54) and cytoplasmic localiazation of HBcAg dominant group(69).There was no statistical difference among four groups in sexes,age,disease course and serum ALT,serum AST,serum HBVDNA with t-test(P＞0.05).(2) The cytoplasmic localiazation of HBcAg group and cytoplasmic localiazation of HBcAg dominant group based mainly on moderate and severe inflammation in liver tissue,showed obvious piecemeal necrosis and lymphocytic infiltration.While the nuclear Iocaliazation of HBcAg group and nuclear localiazation of HBcAg dominant group based mainly on mild inflammation.(3) The serum ALT,AST of cytoplasmic localiazation of HBcAg group were close to upper normal limit and had obvious statistical difference(P＜0.01)after IFN-a therapy,cytoplasmic localiazation of HBcAg dominant group were close to upper normal limit too after IFN-a therapy and have statistical difference(P＜0.05) compare with untreament,while nuclear localiazation of HBcAg group and nuclear localiazation of HBcAg dominant group had no statistical difference compare with untreament(P＞0.05).(4)The seroconversion rate of HBeAg/HBeAb of cytoplasmic localiazation of HBcAg group was highest(70.7%)after IFN-a therapy;and cytoplasmic localiazation of HBcAg dominant group took the second place(58%);the seroconversion rate of the other two groups were low;The seroconversion rate have obvious statistical difference between the cytoplasmic localiazation of HBcAg group and the nuclear localiazation of HBcAg group,the same as the cytoplasmic HBcAg localiazation of dominant group and the nuclear localiazation of HBcAg dominant group(P＜0.01).(5)49 cases of patients'HBVDNA quantitative was less than 1000 copies/ml in cytoplasmic localiazation of HBcAg group after treatment,and 54 cases in cytoplasmic localiazation of HBcAg dominant group whose HBVDNA quantitative was less than 1000 copies/ml.There were still 28 cases of patients'HBVDNA quantitative more than 1000 copies/ml in nuclear localiazation of HBcAg group and 44 cases in nuclear localiazation of HBcAg dominant group.The HBVDNA negative rate had obvious statistical difference between the cytoplasmic localiazation of HBcAg group and the nuclear localiazation of HBcAg group,the same as the cytoplasmic localiazation of HBcAg dominant group compare with the nuclear localiazation of HBcAg dominant group(P＜0.01).(6)Most patients of cytoplasmic localiazation of HBcAg group achieved complete response and only ten of them had no response.In cytoplasmic localiazation of HBcAg dominant group,40 cases of patients achieved complete response,15 cases achieved partial response and 14 cases had non-response.Most cases of patients in nuclear localiazation of HBcAg group and nuclear localiazation of HBcAg dominant group had non-response,were 19 and 22 cases respectively.(7) the higher whose inflammation grade in liver tissue was before therapy,the higher proportion of complete response can gain.(8) The expression of cytoplasmic localisation of HBcAg in hepatocytes was independent influencing factor of IFN-a efficacy by logistic regression analysis. Conclusion:1.The inflammation activity in the liver tissues of cytoplasmic localisation of HBcAg group and cytoplasmic localisation of HBcAg dominant group was higher than that was expressed in nuclear localiazation of HBcAg group and nuclear localisation of HBcAg dominant group.2.The antiviral effect of IFN-a of cytoplasmic localisation of HBcAg group and cytoplasmic localiazation of HBcAg dominant group was obviously better than which of nuclear localisation of HBcAg group and nuclear localisation of HBcAg dominant group.(3) the higher whose inflammation grade in liver tissue was before therapy,the higher antiviral effect can gain.(4) The mechanism of obvious antiviral effect in cytoplasmic localisation of HBcAg group maybe related to the immune clearance phase and immune activation.And,the expression of cytoplasmic localisation of HBcAg in hepatocytes bennifit the reponse of IFN-a.