Quantitation of large, middle and small hepatitis B surface proteins in HBeAg‐positive patients treated with peginterferon alfa‐2a

Abstract

Abbreviations: aa, amino acid; ALT, alanine aminotransferase; AUC, area under the curve; CHB, chronic hepatitis B; CI, confidence interval; ELISA, enzyme-linked immunosorbent assay;HBeAg, hepatitis B e antigen; HBs, hepatitis B surface (protein); HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; LAM, lamivudine; LLOQ, lower limit of quantification;PegIFN, peginterferon alfa-2a; qHBsAg, quantitative hepatitis B surface antigen; ROC, receiver operating characteristic; SC, seroconversion; SHBs/MHBs/LHBs, small/middle/large hepatitis B surface (protein); SVP, subviral particle. Abstract Background & Aims: Hepatitis B virus (HBV) contains three viral surface proteins, large, middle and small hepatitis B surface protein (LHBs, MHBs, SHBs). Proportions of LHBs and MHBs are lower in patients with inactive vs active chronic infection. Interferon alfa may convert hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) to an inactive carrier state, but prediction of sustained response is unsatisfactory. The aim of this study was to test the hypothesis that quantification of MHBs and LHBs may allow for a better prognosis of therapeutic response than total hepatitis B surface antigen (HBsAg) concentration. Methods: Hepatitis B surface proteins were measured before and during peginterferon alfa-2a therapy in serum from 127 Asian patients with HBeAg-positive CHB. Sustained response was defined as HBeAg seroconversion 24 weeks post-treatment.Results: Mean total HBs levels were significantly lower in responders vs nonresponders at all time points (P < .05) and decreased steadily during the initial 24 weeks treatment (by 1.16 vs 0.86 ng/mL in responders/nonresponders respectively) with unchanged relative proportions. Genotype B had a two-fold higher proportion of LHBs than genotype C (13% vs 6%). HBV DNA, HBeAg, HBsAg and HBs protein levels predicted response equally well but not optimally (area under the receiver operating characteristic curve values >0.70). Conclusions:Hepatitis B surface protein levels differ by HBV genotype. However, quantification of HBs proteins has no advantage over the already established HBsAg assays to predict response to peginterferon alfa-2a therapy in HBeAg-positive patients. K E Y W O R D SHBs proteins, HBsAg, peginterferon alfa-2a, predictors of response, subviral particles | 325 RINKER Et al.

A Rapid Immunochromatographic Method Based on a Secondary Antibody-Labelled Magnetic Nanoprobe for the Detection of Hepatitis B preS2 Surface Antigen

“…Most researches on HBsAg focused on the function of the small surface protein of HBsAg. PreS antigen (preS1Ag+preS2Ag) is the N-terminal extension of small surface protein, and the preS antigen, as well as middle and large surface proteins, have gained widespread attention in recent studies on the role of oncogenic risk factors [6], identification of inactive HBV carriers [10], prognosis of therapeutic response [12], and prediction value of HBV infection phases and virological response [37].…”

“…It has a transcriptional transactivator function [8] and contains binding sites for fibronectin, transferrin, and polymerized human serum albumin (pHSA) [9], which are associated with virus entry, release, and active replication. Besides, some studies have shown that the amount and proportions of HBsAg components could be used to identify inactive HBV carriers [10], OBI [11], and predict the response to antiviral therapy [12]. Considering the fact that there have been few reports on clinical preS2Ag detection, it is essential to develop a rapid and quantitative method for preS2Ag.…”

10 Jahre Nationales Referenzzentrum für Hepatitis-B-Viren und Hepatitis-D-Viren in Gießen: Tätigkeiten und Erfahrungen

“…Mit PD Dr. Florian van Bömmel und Prof. Dr. Thomas Berg, Leipzig, wurden neue klinische Biomarker identifiziert, die eine erfolgreiche Therapie bei chronisch HBV-Infizierten anzeigen [ 55 ] und zur Identifizierung von „inaktiven chronischen HBV-Trägern“ beitragen können [ 56 ]. Weitere HBV-relevante Biomarker wurden in Zusammenarbeit mit Prof. Dr. Markus Cornberg und Prof. Dr. Heiner Wedemeyer, Hannover, analysiert [ 57 , 58 ].…”

Novel Biomarkers of Hepatitis B Virus and Their Use in Chronic Hepatitis B Patient Management

“…An alternative ELISA-based method (HBV NRAg; Beijing Wantai Biological, Beijing, China) has been developed to qualitatively detect the PreS1 antigen and HBcAg, with the former having shown surrogate utility for HBV cccDNA activity and HBV replication [ 90 , 91 ]. Furthermore, the measurement of PreS1, or L-HBsAg, using calibrated ELISA assays, has been described in several studies to be associated with detection of residual serum HBV DNA [ 92 ], differentiation of active and inactive CHB, and prediction of functional cure via L-HBsAg to M-HBsAg ratios [ 93 , 94 ], although L-HBsAg levels differ by HBV genotype [ 95 ] which may confound predictive interpretation in diverse populations. The combined detection of conserved amino acid regions within both antigens [ 96 ], which has been termed ‘nucleic acid-related antigen’ [ 97 ], is performed through a dual sandwich ELISA with antigen specific monoclonal antibodies [ 98 ].…”