Clinical Significance Of Hepatic HBsAg Expression In HBeAg-positive Patients Receiving Interferon Therapy

Objective1. To investigate whether the level of Intrahepatic Hepatitis B Virus Markers iscorrelated with serum Hepatitis B Virus Markers in the patients with chronic hepatitisB during the immune clearance phase2.To evaluate the predictive role of HBsAg and HBcAg expression in liver forHBeAg seroconversion in HBeAg positive chronic hepatitis B (CHB) withpegylated interferon α-2a （PEG-IFNα-2a）therapy.MethodsThe data of patients diagnosed chronic hepatitis B(CHB) of the first affiliated hospitalof Fujian medical university was retrospectively analyzed from. Jan of2008to Jan.of2012.all patients were given liver biopsies and the serological and virological dataswere collected simultaneously.The relation between hepatic HBsAg level and serumHBsAg were determined by Spearman’S rank correlation Analysis. Part of the chronichepatitis B (CHB) during the immune clearance phase were given PEG-IFNα-2a(180μg/week，subcutaneously) for48weeks and follow-up for24weeks. Thequantification and expression patterns of HBsAg and HBcAg in the Hepatocytes wereanalyzed after the immunohistochemicalstaining from paraffin-embedded liverbiopsies. The primary antibody was against HBsAg (mouse monoclonal antibody,clone3E7, Dako, Carpinteria, CA, USA). HBcAg were studied using theavidin–biotin immunoperoxidase method (rabbit anti-HBcAg, Neomarkers,Fremont,CA, USA). Patients were divided into two groups: patients who achieved HBeAgseroconversion (responders) after PEG-IFNα-2a therapy; cases in control groupachieved no HBeAg seroconversion after therapy. Two groups of patients werecompared in rate of hepatic HBsAg staining. SPSS17.0software was used for statistical analysis. P<0.05indicated differences with a statistical significance.Result1. According to inclusion and exclusion criteria，the first study bring245cases ofpatients into the group, hepatitis HBsAg was positively correlated with serumHBeAg(r=0.187,P=0.003),HBsAg(r=0.401,P=0.000),HBVDNA(r=0.339,P=0.000),but not related to age,ALT,AST,fibrosis stage or inflammation. hepatitis HBcAg waspositively correlated with serum HBeAg(r=0.213,P=0.001), serum HBsAg(r=0302,P=0.000),HBVDNA(r=0.322,P=0.000),negatively correlated with fibrosisstage (r=-0.137,P=0.035), but not related to ALT,AST or inflammation.2. this study bring71cases of patients into the group, in which responders group has28cases, control group has43cases. In the end of48-week treatment and24-weekfollow-up, the normalization rates of alanine aminotransferase (ALT) were81.7%（57/71）.Virus response rates were77.5%（55/71）. The seroconversion rates ofHBeAg were39.4%（28/71）at the end of follow-up. Five patients achieved HBsAgloss, including one with HBsAg seroconversion at the end of follow-up. Age, gender,inflammation grade and fibrosis stage, ALT, HBeAg, HBV-DNA levels, total hepaticHBsAg and HBcAg expression were similar in patients with HBeAg seroconversion(responders) versus those without (non-responders) at baseline. HBsAg cellmembrane positive staining were much lower in responders compared tonon-responders before treatment(P=0.045), and quantitative serum HBsAg was lowerin responders (3.84±0.95VS4.27±0.61,P=0.029);Multivariate analysis revealedthat HBsAg cell membrane positive staining was the only independent predictor ofHBeAg seroconversion still (OR=3.1295%CI=1.062-9.158P=0.039).Conclusions1. Serum HBsAg concentration can reflect the intensity of hepatitis HBsAg in thepatients with chronic hepatitis B during the immune clearance phase2. Pretreatment HBsAg cell membrane expression in liver may predict sustainedHBeAg seroconversion in HBeAg positive CHB patients with PEG-IFNα-2a therapy.