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Chronic HBV Infection: Analysis Of T Helper Cells Function And Influence Of Lamivudine Therapy

Posted on:2004-12-03Degree:MasterType:Thesis
Country:ChinaCandidate:D M HeFull Text:PDF
GTID:2144360095961367Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
There are various liver injury type of hepatitis B virus (HBV) infection, include acute hepatits B (AHB), chronic hepatits B (CHB), chronic asympotomatic HBV carrier (AsC), liver cirrhosis (LC) and hepatic cellular cancer (HCC). Chronic HBV infection is a major health threat and the main cause of end-stage liver disease in our country. AsC and CHB are the most important types of these. There are various infection situations from low to high lever viremia in AsC. Cytokines play an important role in the defense against viral infections, both indirectly, through determination of the predominant pattern of host response, and directly, through inhibition of viral replication. However, in the context of an inflammatory response against a virus, cytokines may also lead to liver damage. T-helper (Th) cells are in the center of anti-HBV immunity. Interleukin-12 (IL-12) is a heterodimeric cytokine produced by antigen-presenting cells that has the ability to induce gamma interferon (IFN-gamma) secretion by T and natural killer cells and to generate normal Th1 responses. Th1 type cytokines include IL-2, IFNγ and TNFβ, and exert important role in anti-virus immunity. Th2 type cytokines include IL-4, IL-5, IL-6, IL-10 and IL-13,mainly participate in humoral immunity. Activity of CHB is associated with the imbalance of cellular immunity. The balance between Th1 and Th2 cells specific for the HBc/HBeAgs may be relevant in acute and chronic HBV infections. The imbalance of Th cytokine production may play an important role in immunopathogenesis of persistent HBV infection. Lamivudine (LAM,3TC) is a kind of nucleoside analogues, and obtains wide application in HBV infection correlated diseases, especially in CHB. Lamivudine exerts effect by downregulating HBV DNA polymerase activity, but have no effect on virus mRNA. For this reason, patient's serum HBV DNA lever declined rapidly but HBeAg conversed slowly, even no seroconversion could be found. The patients obtain HBeAg/HBeAb seroconversion obviously by to influence on the cellular immunity of body.To explore the difference among different HBV infection situation, to assess the cellular immunity function of who infected by HBV in addition to the common markers,such as liver function, HBV markers, HBV DNA, et al, to explore the change of the cellular immunity after lamivudine therapy and the difference of correlate immune factors in different response degree, to try to find reasonable, practical and brief markers to predict the effect of lamivudine therapy, the lever of Th1 type cytokines (IL-2,IFNγ), Th2 type cytokines (IL-4,IL-10) and IL-12 were detected in a series sera of patients infected by HBV and CHB before and after lamivudine therapy. Chronic HBV infection: Analysis of Th cell functionIL-12 may have an important role for viral clearance in chronic HBV infection. Lack of IL-12 is an important cause of high lever HBV DNA in some CHB. Application of IL-12 can alter Th2 dominant response to Th1. The cytokines released by Th cells also play an important role in downregulation of HBV replication, demonstrating that it is possible to control HBV infection without the death of infected hepatocytes. However, if there is a defect in the acute response, HBV infection becomes chronic. Th1 type cytokines exert main role in the immune clearance of HBV. IFNγ can be the identification marker of Th1 cells and IL-4 can be Th2 cells. The imbalance of Th cells subtypes can disturb seriously the immunity function. Acute HBV infection is resolved in the context of an efficient cell-mediated immune (CMI) response, whereas, chronic infection is characterized by weak to undetectable CMI responses and relatively efficient humoral immunity. At present, anti-virus therapy is not recommended for AsC. Although HBV can be eliminated in most of AsCs after long period of virus carrying, the longer period of HBV carrying is an important factor induced end-stage liver disease. It is not the best selection for AsC not to give any therapy.The study showed that high leve...
Keywords/Search Tags:hepatitis virus B, hepatitis B, chronic, chronic asympotomatic HBV carrier, T helper cells, Interleukin-2, Interleukin-4, Interleukin-10, Interleukin-12, gamma interferon, Th1 type cytokine, Th2 type cytokine, Th1/Th2 balance, lamivudine
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