| Object In recent years, research has shown that progress of chronic hepatitis B (CHB) and liver cancer has a clear correlation with replication of hepatitis B virus (HBV). On this basis, the antiviral treatment has gradually become the main treatment of chronic hepatitis B. Telbivudine is a nucleoside analogue drug newly listed.Phase3clinical trial results both at home and abroad have showed that the drug has a high hepatitis B e antigen (HBeAg) serum conversion rate in addition to prompting the strong inhibition of virus, especially for chronic hepatitis B patients with alanine aminotransferase (ALT) of2times or more,whose HBeAg seroconversion rate is significantly higher than patients of other nucleoside drugs.Results suggest that Telbivudine may affect the body’s immune system during the treatment process.But the exact mechanism is unclear. Relevant experiments on animals suggest that Telbivudine can not only increase the interferon levels in the blood of the rats infected by mouse hepatitis virus, but also can reduce the secretion of interleukin4(IL-4). But the influence mechanism of Telbivudine to the immune system of human body is still less reported. The T cell receptor type spectrum analysis technology (named TCR CDR3spectrum analysis technology) is used for the study of the treatment of patients with chronic hepatitis B virus, in order to understand the influence of Telbivudine on the mechanism of the immune system.Methods (1) In our hospital15cases of patients with chronic hepatitis B (CHB) are selected as research objects,whose peripheral blood of baseline is separately collected, compared with healthy blood donation members.(excluding infection, tumor and autoimmune diseases, etc);(2)Indicators of HBV DNA and liver function such as ALT and AST are detected during the same period before and after treatment. Five quantitative determination of hepatitis B is carried on to analysis how hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg) change.The result is used for the study of pertinence analysis with the variation of HBV DNA;(3) The peripheral blood of each research object is collected at6ml,by which density gradient centrifugation is used to isolate peripheral blood mononuclear cells.Then cell separated,RNA extracted with the use of TRIZOL reagent,synthesis of complementary DNA (cDNA), PCR amplification is on progress;(4) CDR3spectral is analyzed by GeneScan.Results Levels of15cases of chronic hepatitis B patients with HBV-DNA quantitative (after logarithmic transformation) before and after treatment in6months are:6.67±0.92,2.76±0.39.The number after6months significantly decreased compared with before treatment (P<0.01);Numbers of hepatitis B surface antigen (HBsAg) drop degree before and after treatment are:25181±9835,11917±6453.Compared with it before treatment, the number decreased obviously after6months (P<0.01); Numbers of hepatitis B e antigen (HBeAg) drop degree before and after treatment are:203.15±177.92,46.06±22.92.Compared with it before treatment, the number decreased obviously after6months (P<0.01);Numbers of ALT before and after6months treatment of liver function are:203.15±177.92,46.06±22.92. Compared with it before treatment, the number decreased obviously after6months(P<0.01); Numbers of AST before and after6months treatment of liver function are:166.54±156.50,40.20±15.96. Compared with it before treatment, the number decreased obviously after6months(P<0.01). Decline of drop degrees of HBsAg is liner with the decline of HBV-DNA level. The result of Pearson correlation test is r=0.910, p=O.OOO.Serum HBeAg drop degree decreases after6months of antiviral treatment,as the decline of serum HBV-DNA levels, and the results are positively related. Spearman correlation analysis shows that the correlation coefficient between them is r=0.636, p=0.011.10CDR3spectrum of15cases are completed.Abnormal spectrum types appear more or less in the β chain V area CDR3spectrum types of peripheral blood before and after the treatment in all10cases.The statistical of total number of families which appear abnormal spectrum types of each case before and after antiviral therapy shows that the average number of families which appear abnormal spectrum types in24families in TCR CDR3is5.40±2.07before treatment, as the average number is5.20±1.81after treatment.The total number of families which appear abnormal spectrum type before and after treatment has at test analysis. The results show that there is no statistically significant differenced=0.238, P=0.817. But all24BV families have obvious phenomena of spectrum type change specific to each case.Conclusion Serological index of chronic hepatitis B patients has obvious changes after antiviral treatment of taking Telbivudine.Elevated ALT decreased to a normal level.HBV DNA overcasts.At the same time it detected that HBsAg, HBeAg drops fell significantly.Decline of HBsAg and HBeAg drop degrees are liner with the drop of HBV-DNA level.For10cases before and after treatment with Telbivudine,although there is no statistically significant difference in the total number of families which appear abnormal spectrum types in24families in TCR CDR3,each case has a change in spectrum type. |
PDF Full Text Request