Z Gastroenterol 2014; 52 - P_5_38
DOI: 10.1055/s-0033-1361047

Quantification of Large, Middle and Small Hepatitis B virus (HBV) surface protein (HBsAg) fractions in patients with Hepatitis Delta

SB Wiegand 1, B Bremer 1, A Geipel 2, CM Bremer 2, A Wranke 1, B Heidrich 1, MP Manns 1, H Wedemeyer 1, D Glebe 2, M Cornberg 1
  • 1Medical School Hannover, Department of Gastroenterology, Endocrinology and Hepatology, Hannover, Germany
  • 2Justus Liebig University, National Research Center for Hepatitis B and D viruses, Gießen, Germany

Background and aims: HBsAg itself is regarded as the sum of three HBV-surface-proteins present on virions and subviral particles. They are co-carboxyterminal proteins called large (L-), middle (M-) and small (S-)HBs that differ in aminoterminal sequences and glycosylation status (preS1/preS2 in LHBs; N-glycosylated preS2 in MHBs, SHBs in all proteins). Commercial HBsAg-tests can only determine the total amount of HBsAg but variations in their protein composition and posttranslational modifications are not covered that could reflect specific host responses, since preS-domains cover B-and T-cell epitopes. LHBs contains preS1 and is necessary for receptor-binding and thus entry of HDV into hepatocytes. So far no study explored HBsAg fractions in Hepatitis Delta patients. This may be relevant for the development of biomarkers, i.e. to predict treatment response to IFN.

Patients and methods: We used well-defined monoclonal Abs (mAbs) against the preS1-domain (LHBs), the N-glycosylated preS2-domain (only in MHBs) and the S-domain (L-, M-, SHBs) covering HBV genotypes A-H to detect and quantify differences in the composition of serum HBsAg concerning the three surface proteins. We analyzed HBsAg fractions in twenty-five well-defined patients with HDV infection and compared our findings with results of HBsAg fractions in fifteen acute hepatitis B (AHB) patients and twenty-one patients with chronic hepatitis B virus monoinfection.

Results: Hepatitis delta infection resulted in highest ratios in LHBs compared to AHB and CHB with 14,10 ± 7,70%, 4,62 ± 3,23% and 10,03 ± 5,29% respectively (p < 0,001; p < 0,05), lower MHBs compared to CHB with 3,07 ± 3,31% to 13,21 ± 9,95% (p < 0,001) and lower SHBs compared to AHB 82,84 ± 9,80% to 90,91 ± 7,01% (p < 0,01).

Conclusion:

This is the first study investigating the ratio of L-, M-, SHBs in patients with Hepatitis Delta, demonstrating differences in HBsAg fractions between Hepatitis Delta, acute and chronic HBV monoinfection. Higher LHBs-ratios in Hepatitis Delta might be one reason for a strong infectivity of Hepatitis Delta. Future studies have to elaborate if LHBs levels may be a better marker compared to total HBsAg to predict response to IFN during HDV-therapy.