Clinical Study Of Hepatitis B Virus Large Protein In Chronic Hepatitis B Patients' Sera

Objective: Hepatitis B virus (HBV) infection is a problem of influence global health problem. At present HB infection was a giant colony in our country.In clinic, HBeAg and HBV DNA were often used as signals to judge HBV replication and infection. When HBV pre-C or C region has mutation, HBeAg is negative but HBV still keeps replication, so at that time it is difficult to determine cure opportunity according to HBeAg. While in the process of antiviral therapy, the change of HBV copy numbers is a main target to evaluate the therapeutic effect.The nucleoside analogue, which was an antiviral drug, can merely inhibit the replication of HBV DNA, but cannot restraint the transcription and translation of HBV DNA which has formed so it is insufficient to detect HBV DNA and HBeAg. We should detect the proteins, which have the functions of trans-activation viral replication and can directly lead to hepatic injury, to identify the cure opportunity. As a result, LHBsAg could be chosen.Concerned research indicated that HBV surface large protein (LHBsAg) played a key role in viral persistence, viral reaction after treatment withdrawal, and drug resistance. LHBsAg is a unique capsid-envelope protein charactered with peculiar dual trans-membrane topology, hepatic injury and trans-activation for virus replication.The aim of this study was to evaluate the relationship of LHBsAg expression degree and HBeAg, HBV DNA, how HBV genotypes and HBV cccDNA in PBMC influence its serum level. To evaluate the LHBsAg clinical significance in the diagnosis, treatment and prognosis monitoring of CHB, application value of LHBsAg as a easily carrying out sera index.Methods: Selected 659 CHB patients at random. Enzyme linked immunosorbent assay (ELISA) were used to detect LHBsAg. Fluorescent quantitative PCR were used to detect HBV DNA, HBV genotypes B and C and HBV cccDNA in peripheral blood mononuclear cells(PBMC)and serum. Linear correlation, chi square test and t test were performed.Results:1. There was a positive correlation between the LHBsAg quality and HBV DNA logarithm level in the sera(r=0.434,P=0.0001,P<0.05). The LHBsAg positive rate was higher than HBV DNA positive rate (P<0.05).2. LHBsAg positive rate was higher in PreS1Ag positive group of HBsAg-HBeAb-HBcAb mode. There was no statistics difference in the LHBsAg and PreS1Ag positive rates of HBsAg-HBeAg-HBcAb mode and HBsAg-HBcAb mode.3. 47 CHB patients were selected to detected HBV genotypes, there were 5(10.64%), 39(82.98%), 1(2.13%) and 2(4.26%) were respectively classified as genotype B,genotype C, mixed and undefined genotype. There was no statistics difference between the 35 LHBsAg positive of 39 genotype C cases and 4 LHBsAg positive of 5 genotype B cases (P>0.05).4. There are 2 HBV cccDNA positive of 30 PBMC cases. HBV cccDNA could not be detected in sera. 3 cases PBMC HBV DNA detected positive, while their sera detected negative.5. LHBsAg quantity descended along with liver inflammation and fibrosis degree aggravation. There was no statistics difference in the ALT quantity in LHBsAg positive sera and negative sera (P>0.05). We could not consider LHBsAg were correlated with liver inflammation and fibrosis degree.6. LHBsAg positive rate was higher than HBeAg of the three groups (<1.0×10~3, 1.0×10~3~ and 1.0×10~6~). LHBsAg positive rate was higher than HBV DNA of HBsAg-HBeAb-HBcAb mode and HBsAg-HBcAb mode.Conclusion:1. The cooperative detection of sera LHBsAg and HBV DNA was more sensitive for estimating the state of HBV replication than other methods. It could be an evaluating curative effect and treatment opportunity. LHBsAg was more sensitive than HBV DNA. LHBsAg was more sensitive than PreS1Ag of HBsAg-HBeAb-HBcAb positive mode. Different HBV genotypes did not influent the sera LHBsAg content. The sera LHBsAg content was not suitable to reflect liver inflammation and fibrosis degree aggravation. LHBsAg was reliable to reflect HBV replication of HBeAg negative CHB patients.2. It was simple to use the structural monoclony antibody of high appetency and high specity, to establish enzyme linked immunosorbent assay detecting LHBsAg was one of the easily method to develop. LHBsAg could reflect HBV replication state, there was important clinical significance and high extend using value. LHBsAg was a good complementary index in the lab of HBV DNA detecting, LHBsAg also had great foreground in the lab of no HBV DNA detecting.