E Antigen Expression in Hepatitis B Virus Infection Is Associated with Core Antigen Expression and More Severe Disease Activity
Kathy R Kawaguchi, Lihui Qin, Ya-Lin Chiu, Monique J Carasso, Ira M Jacobson, Rhonda K Yantiss. Weill Cornell Medical College, New York, NY
Background: Patients with chronic hepatitis B (HBV) infection may have detectable serum E antigen (HBeAg), reflecting actively replicating virus, whereas absence of HBeAg denotes an inactive carrier state or infection with precore-mutated virus. Data regarding the relationships between HBeAg status, immunohistochemical staining patterns for hepatitis B core (HBcAg) and surface (HBsAg) antigens, and severity of liver disease are conflicting. The purpose of this study was to evaluate the associations, if any, between HBeAg status and these other parameters.
Design: 103 patients with chronic HBV-related hepatitis and known HBeAg status were included in the study. Liver biopsies from all patients were assessed for inflammation and fibrosis using a four-tiered system. Each case was subjected to immunostains for HBcAg and HBsAg. The Wilcoxon Ranked Sum Test and Spearman Rank Correlation Test were used to examine associations between histologic (inflammatory activity, fibrosis, percentage of HBcAg- and HBsAg-positive hepatocytes), clinical (age, sex, ethnicity, genotype), and serologic (HBeAg, HBV DNA titers, ALT) findings.
Results: 38 patients (M/F=11/8, mean age: 34 years) were HBeAg+, 18 (47%) of whom were born outside the U.S., and 65 patients (M/F=31/34, mean age: 44 years) were HBeAg-, including 48 (74%) born outside the U.S. and 17 (26%) with precore mutation. Overall, HBeAg+ patients had more hepatic inflammation (p<0.05) and fibrosis (p<0.05), more extensive HBcAg staining (p<0.05), and higher HBV DNA titers (p<0.05) and ALT levels (p<0.05) than HBeAg- patients. Extent of nuclear and cytoplasmic HBcAg staining reflected increased HBV DNA titers in both groups, denoting active viral replication. However, extent of HBcAg staining was also associated with inflammation (p<0.05) and fibrosis (p<0.05) in HBeAg- patients. The extent of HBsAg staining was not associated with any histologic or clinical parameters in either group.
Conclusions: HBeAg is a marker of viral replication and usually reflects immune tolerance, clearance, or reactivation in chronically infected patients. Thus, HBeAg+ patients usually have more active HBV-related liver disease than HBeAg- patients, although HBcAg and HBsAg are not helpful in their evaluation. These markers may be helpful in HBeAg negative cases because their staining patterns can be used to subclassify patients. Those who are HBcAg-/HBsAg+ or HBcAg-/HBsAg- are likely in the inactive carrier state, whereas those with HBcAg+ probably harbor HBV with precore mutations.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 238, Wednesday Morning