| Objectives: Hepatitis B Virus (HBV) infection is a global health problem. There are more than 350 million people with chronic HBV infection in the world. Based on the statistics of World Health Organization, there are more than 1 million people deathing from HBV infection per annum. Among patients with Chronic Hepatitis B Virus(CHB), about 15 to 25 percent of them death from hepatic cirrhosis or primary carcinoma of the liver. In the history of HBV infection, it is always the disappearance of viremia or the resolution of inflammation accompanying with HBeAg negative. But in some patients, HBeAg seroreversion don't indicate the resolution of infla-mmation. The condition of HBeAg negative with viremia is defined as HBV infection with HBeAg negative the condition of HBeAg negative with viremia. It is a common problem, which is the second state of CHB and is as important as CHB with HBeAg positive. The mechanism resulting from HBV infection with HBeAg negative is very complex. So far there are several explanations about viral mutation. In the transcription level, mutation in the core promoter (CP) suppresses precore mRNA transcription, leading to a dramatic decrease of HBeAg expression. A double mutation in the BCP which converts nucleotide (nt ) 1762 from A to T and nt1764 from G to A was often observed. In the translation level , the viral factor which inhibits the secreting of HBeAg is mainly the mutation in the precore region, including A1896 (PreC stop codon ) mutation and initiating codon mutation. In the past translation, the viral factor which affects the forming of HBeAg is the mutation at nt1862 ( from C to T ) . With the infection by HBV, individuals'specific immune response could be provoked. The types and grade of immune response decide the outcome of infection. Immunological studies found that helper T cells (Th ) can be divided into Th0, Th1 and Th2. Th1 mainly secrets Th1 cytokines, such as IL-2,IL-12 and γ-IFN, leading mainly to cellular immune response. But Th2 mainly secrets Th2 cytokines, such as IL-4,IL-10, mainly inducing humoral immune response. The studies revealed that Th1 played an important role in the process of resisting virus. Gene chip ( or DNA microarray ) is a biological technique which is gradually developed in later years, it can be used to detect gene mutation. It makes use of the techniques of PCR and chip hybridization. After HBV-DNA is extracted from the patient's serum , target gene is marked by fluorescence and amplified . Then it is hybridized with the probes on the gene chip . Finally,the hybridization signals produced are examinedby the computer . In this study , our aims were ①to explore the proportion of HBV infection with HBeAg negative. ②to study the HBV gene mutation and their correlation with HBV-DNA level and liver function by gene chip. ③to explore the effect of HBV gene mutation on immunological function . Methods : Selecting the patients with HBV infection as studied objects, who once visited digestive department, the second hospital of Hebei Medical University from March to October, 2004. At the same time, selecting 20 healthy people as control . Inclusion criteria : ①HBV markers : HBsAg ,HBeAb and HBcAb positive, HBsAb,HBeAg negative; ②ALT ≤250 IU/L ; ③AGE : 16～60 years old. Exclusion criteria : ①Accompinied by other types of viral hepatitis or/and alcoholic hepatitis, drug-induced hepatitis,fatty hepatitis,autoimmune hepatitis; ②Using immunosuppressed or immunoenhanced medications recently; ③hepatic cirrhosis or primary carcinoma of the liver ;④Total bilirubin ﹥2 times the ULN(Upper Limit of Normal)。Firstly the patients included were detected HBV-DNA, liver function and abdominal ultrasonography. Then the patients with positive HBV-DNA were studied to detect the HBV gene mutation through gene chip. The important steps as follows : 1 Treating of serum sample : ①adding into the tubepatient's serum 10 μl and HBV lytic solution 10 μl , shaking up, 37℃for 1 hour. ②adding neutralizing solution 20 μl, shaking up and centrifug...
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