Clinical Study Of Autologous Dendritic Cell Vaccine Combined With Lamivudine In Tratment Of Chronic Hepatitis B Patients

Hepatitis B (hepatitis B) is a global infectious disease which caused by the hepatitis B virus (HBV), mainly injured the liver. About 2 billion people were infected, of those about 300-400 million remain chronically infective. China is defined as high prevalence country with 9.09% of the national population infected, 25% of those had chronic liver disease which is closely related with cirrhosis and liver cancer.Hepatitis B virus (HBV) infection is a major global health concern and accounts for the highest morbidity and mortality of infectious diseases. In china, more than 100 million people each year die from HBV-related chronic liver disease, including cirrhosis, hepatocellular carcinoma (HCC) and so on.At present,the treatment of chronic hepatitis B mainly depended on nucleoside analogues such as amivudine,EntikaweiPian.Nucleotide analogues mark a significant advance in suppressing HBV replication, but they can't completely eliminate the virus.However, nucleoside therapies usually require long-term administration and up to 60% or more of HBV strains varied after two years of lamivudine treatment. In recent years, several cytokines such as IFN-a and pegylated IFN-a began to be used in the treatment of hepatitis B. Interferon plays a role in eliminating the virus, but only effective in about 30% of patients in china. It is because the HBV prevalent in china mainly in the B-and C-types are not sensitive to interferon, which requires people to seek new treatments.It is found that Chronic hepatitis B patients with immune tolerance to the virus, the anti-viral CD4+ and CD8+ T cell response was significantly reduced in chronic hepatitis B. As the HBV-specific CTL can not effectively clear the virus, which may cause the persistence of the virus. Immune tolerance in CHB patients may be associated with the lower number and function of Dendritic cell. Dendritic cells(DC),the most powerful antigen presenting cell, expresses major histocompatibility complex, B7 costimulatory molecules and adhesion molecules, Secretes IL-12.DC is the initiator of the immune response can induce the primary immune response by activating naive T cells. It is also found the number of DC is negatively related with HBV DNA in CHB patients. The immune tolerance to HBV may be break by improving the number and function of DC. There are many attempts to treat patients with hepatitis B by transfering DC which cultured in vitro and loaded with associated antigen to the patients, but the efficacy is not very precise.In this study, we use DC vaccine plus lamivudine to treat the CHB patients. Beside the antivirus effect of lamivudine, this strategy also break immune tolerance and promote the body's cellular immune response to clear the remaining virus by improving the number and function of DC.So it may be a good strategy and reduce the patient's long-term dependence on antiviral drugs.We choose 53 CHB patients who were treated in our hospital from 2008 to 2009. We set three different groups, Lamivudine group, DC vaccine group and DC vaccine plus Lamivudine group.1 Preparation of DC vaccine loaded with HBsAg:PMBC isolated from CHB patients were incubated with GM-CSF and IL-4. The HbsAg was added on day 6 and DC was collected on day 7. During the days, we observed the cell morphology and identified the dendritic cell surface marker CD1a CD83 using flow cytometry. We successfully cultured matured DC in vitro and loaded with the HBsAg.2 We didn't get desired results of the treatment on patients with chronic hepatitis B when used DC vaccine alone. The levels of HBV DNA and biochemical indexes of liver function (ALT AST TIBL ALB) increased than before, but which wasn't statistical significance.3 Lamivudine played a role in treating the patients with chronic hepatitis B when used alone, the levels of HBV DNA and biochemical indexes of liver function (ALT AST TIBL) declined greater than before, of which the level of TIBL declined than before significantly(P<0.05).The level of albumin (ALB) increased than before,but which wasn't statistical significance.4 DC combined with lamivudine played a significant role in treating the patients with chronic hepatitis B. The levels of HBV DNA decreased significantly than before (P<0.01), and the levels of biochemical indexes of liver function (ALT AST TIBL) declined than before significantly (P<0.05).However the level of albumin (ALB) increased than before, but which wasn't statistical significance.Conclusion:The results show that DC vaccine plus lamivudine played a better role in treating the patients with chronic hepatitis B than DC vaccine and lamivudine alone. So it is expected to be a short-term, effective and stable strategy for the chronic hepatitis B to overcome the shortcomings of antiviral therapy.