Z Gastroenterol 2019; 57(01): e86
DOI: 10.1055/s-0038-1677276
5. Viral Hepatitis, Immunology
Georg Thieme Verlag KG Stuttgart · New York

Loss of the middle hepatitis B virus (HBV) surface antigen (MHBs) during interferon-alpha (PEG-IFN) treatment is associated with subsequent lower HBV replication in patients with chronic HBeAg negative hepatitis B

M Pfefferkorn
1   University Clinic Leipzig, Department of Gastroenterology and Rheumatology, Section of Hepatology, Leipzig, Germany
,
T Schott
1   University Clinic Leipzig, Department of Gastroenterology and Rheumatology, Section of Hepatology, Leipzig, Germany
,
C Felkel
1   University Clinic Leipzig, Department of Gastroenterology and Rheumatology, Section of Hepatology, Leipzig, Germany
,
S Böhm
2   Ludwig Maximilians-University, Max von Pettenkofer-Institute for Hygiene and Clinical Microbiology, Munich, Germany
,
R Heyne
3   Liver and Study Center Checkpoint, Berlin, Germany
,
D Glebe
4   4Justus-Liebig University Gießen, National Reference Centre for Hepatitis B and D viruses, Institute for Medical Virology, Gießen, Germany
,
T Berg
1   University Clinic Leipzig, Department of Gastroenterology and Rheumatology, Section of Hepatology, Leipzig, Germany
,
F van Bömmel
1   University Clinic Leipzig, Department of Gastroenterology and Rheumatology, Section of Hepatology, Leipzig, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
04 January 2019 (online)

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    Background and Aims:

    Since functional cure of HBV occurs rarely in HBeAg negative patients during treatment with pegylated Interferon-alpha (PEG-IFN), a transformation into a disease stage with lower HBV replication might be considered an alternative goal. HBsAg consists of the components large (L), middle (M) and small (S)HBs, and the composition of HBsAg shows a strong association to HBV disease stages. We have investigated whether kinetics of MHBs or LHBs in serum is associated with response to PEG-IFN treatment.

    Methods:

    HBsAg components were quantified using a semi-automatic validated ELISA with monoclonal antibodies for L- (LOD = 0.03 ng/mL) and MHBs (LOD = 0.47 ng/mL) as well as polyclonal antibodies for SHBs/total HBsAg (LOD = 0.08 ng/mL; HBsAg 6.0, Enzgnost, Siemens). Serum levels of HBV DNA were quantified using the COBAS AmpliPrep/COBAS TaqMan HBV kit (LOD: 35 copies/mL; Roche Diagnostics). HBeAg negative patients (n = 12) with HBV mono infection (9 male, mean age 41.1 ± 9.6 (29 – 56) years) receiving PEG-IFN treatment for 48 weeks were observed for a mean of 95.1 ± 21.3 (range, 60 – 132) weeks. Patients were categorized HBsin two groups by changes in HBsAg levels: decrease of total HBsAg > 1 log (A, n = 4) or < 1 log ng/mL (B, n = 8) at week 72.

    Results:

    Before PEG-IFN treatment, mean total HBsAg levels (3.6 ± 3 vs. 4.3 ± 4 log10 ng/mL; p = 0.114) as well as the ratios of LHBs (4.0% vs. 4.4%; p = 0.476) and MHBs (3.7% vs. 5.1%; p = 0.171) were similar in groups A and B. During PEG-IFN treatment, mean total HBsAg decreased in group A from 3.3 ± 3.2 at week 12 to 0.3 ± 0.7 log10 ng/mL at week 48, respectively (p = 0.029). In group B, no significant decrease of HBsAg levels was detected. At week 72, HBsAg levels were 0.8 ± 1 vs. 3.7 ± 4.2 log10 ng/mL in groups A and B (p = 0.067). MHBs ratios showed a decrease in group A as compared to group B by weeks 12, 24, 36 and 48, respectively (2.7% vs. 8.2%, p = 0.089; 1.2% vs. 9.7%, p = 0.028; 0% vs. 10.1%, p = 0.006; 0% vs. 12.1%, p = 0.006). At week 72, MHBs was 0.74% and 6.1% in groups A and B (p = 0.019). LHBs ratios showed no significant differences between both groups throughout the observation period. HBV DNA decreased similarly in both groups and was < 100 IU/mL during PEG-IFN treatment in all patients. At week 72, HBV DNA levels were (A) 1.7 ± 2.6 cp/mL vs. (B) 3.4 ± 3.4 cp/mL, respectively (p = 0.038).

    Conclusions:

    We could show that decreased HBV replication following treatment with PEG-IFN is associated with an early decrease of MHBs. In contrast, patients without serological response to PEG-IFN treatment showed no change or an early increase of ratios of MHBs. Our findings need to be confirmed in larger cohorts and the underlying mechanism of changes in HBsAg composition needs to be explored.


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