Serum O-glycosylated hepatitis B surface antigen levels in patients with chronic hepatitis B during nucleos(t)ide analog therapy
Abstract Background Serum hepatitis B surface antigen (HBsAg) is a component of both hepatitis B virus (HBV) virions and non-infectious subviral particles (SVPs). Recently, O-glycosylation of the PreS2 domain of middle HBsAg protein has been identified as a distinct characteristic of genotype C HBV...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Gastroenterology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12876-022-02352-4 |
| _version_ | 1817970534079528960 |
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| author | Ayato Murata Kiyohiko Angata Maki Sogabe Shunsuke Sato Takafumi Ichida Hisashi Narimatsu Takuya Genda |
| author_facet | Ayato Murata Kiyohiko Angata Maki Sogabe Shunsuke Sato Takafumi Ichida Hisashi Narimatsu Takuya Genda |
| author_sort | Ayato Murata |
| collection | DOAJ |
| description | Abstract Background Serum hepatitis B surface antigen (HBsAg) is a component of both hepatitis B virus (HBV) virions and non-infectious subviral particles (SVPs). Recently, O-glycosylation of the PreS2 domain of middle HBsAg protein has been identified as a distinct characteristic of genotype C HBV virions versus SVPs. This study aimed to evaluate serum O-glycosylated HBsAg levels in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogs (NAs). Methods Forty-seven treatment-naïve patients with genotype C CHB were retrospectively enrolled. Serum O-glycosylated HBsAg levels at baseline and after 48 weeks of NA therapy were quantified by immunoassay using a monoclonal antibody against the O-glycosylated PreS2 domain of middle HBsAg, and their correlations with conventional HBV marker levels were analyzed. Results At baseline, the serum O-glycosylated HBsAg levels were significantly correlated with the HBV DNA (P = 0.004), HBsAg (P = 0.005), and hepatitis B-core related antigen (HBcrAg, P = 0.001) levels. Both HBV DNA and O-glycosylated HBsAg levels were decreased after 48 weeks of NA therapy. The significant correlation of the O-glycosylated HBsAg level with the HBsAg or HBcrAg level was lost in patients who achieved undetectable HBV DNA (HBsAg, P = 0.429; HBcrAg, P = 0.065). Immunoprecipitation assays demonstrated that HBV DNA and RNA were detected in the O-glycosylated HBsAg-binding serum fraction, and the proportion of HBV RNA increased during NA therapy (P = 0.048). Conclusion Serum O-glycosylated HBsAg levels change during NA therapy and may reflect combined levels of serum HBV DNA and RNA virions. An O-glycosylated HBsAg-based immunoassay may provide a novel means to monitor viral kinetics during NA therapy. |
| first_indexed | 2024-04-13T20:35:35Z |
| format | Article |
| id | doaj.art-951e6b81fe904975b019bf2f2a7050bb |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-04-13T20:35:35Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-951e6b81fe904975b019bf2f2a7050bb2022-12-22T02:31:03ZengBMCBMC Gastroenterology1471-230X2022-05-012211810.1186/s12876-022-02352-4Serum O-glycosylated hepatitis B surface antigen levels in patients with chronic hepatitis B during nucleos(t)ide analog therapyAyato Murata0Kiyohiko Angata1Maki Sogabe2Shunsuke Sato3Takafumi Ichida4Hisashi Narimatsu5Takuya Genda6Department of Gastroenterology and Hepatology, Juntendo University Shizuoka HospitalResearch Core for Medical GlycoScience (RCMG) IncResearch Core for Medical GlycoScience (RCMG) IncDepartment of Gastroenterology and Hepatology, Juntendo University Shizuoka HospitalDepartment of Hepatology, East Shonan ClinicResearch Core for Medical GlycoScience (RCMG) IncDepartment of Gastroenterology and Hepatology, Juntendo University Shizuoka HospitalAbstract Background Serum hepatitis B surface antigen (HBsAg) is a component of both hepatitis B virus (HBV) virions and non-infectious subviral particles (SVPs). Recently, O-glycosylation of the PreS2 domain of middle HBsAg protein has been identified as a distinct characteristic of genotype C HBV virions versus SVPs. This study aimed to evaluate serum O-glycosylated HBsAg levels in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogs (NAs). Methods Forty-seven treatment-naïve patients with genotype C CHB were retrospectively enrolled. Serum O-glycosylated HBsAg levels at baseline and after 48 weeks of NA therapy were quantified by immunoassay using a monoclonal antibody against the O-glycosylated PreS2 domain of middle HBsAg, and their correlations with conventional HBV marker levels were analyzed. Results At baseline, the serum O-glycosylated HBsAg levels were significantly correlated with the HBV DNA (P = 0.004), HBsAg (P = 0.005), and hepatitis B-core related antigen (HBcrAg, P = 0.001) levels. Both HBV DNA and O-glycosylated HBsAg levels were decreased after 48 weeks of NA therapy. The significant correlation of the O-glycosylated HBsAg level with the HBsAg or HBcrAg level was lost in patients who achieved undetectable HBV DNA (HBsAg, P = 0.429; HBcrAg, P = 0.065). Immunoprecipitation assays demonstrated that HBV DNA and RNA were detected in the O-glycosylated HBsAg-binding serum fraction, and the proportion of HBV RNA increased during NA therapy (P = 0.048). Conclusion Serum O-glycosylated HBsAg levels change during NA therapy and may reflect combined levels of serum HBV DNA and RNA virions. An O-glycosylated HBsAg-based immunoassay may provide a novel means to monitor viral kinetics during NA therapy.https://doi.org/10.1186/s12876-022-02352-4Hepatitis B virusHepatitis B surface antigenO-GlycanPregenomic RNAVirion |
| spellingShingle | Ayato Murata Kiyohiko Angata Maki Sogabe Shunsuke Sato Takafumi Ichida Hisashi Narimatsu Takuya Genda Serum O-glycosylated hepatitis B surface antigen levels in patients with chronic hepatitis B during nucleos(t)ide analog therapy BMC Gastroenterology Hepatitis B virus Hepatitis B surface antigen O-Glycan Pregenomic RNA Virion |
| title | Serum O-glycosylated hepatitis B surface antigen levels in patients with chronic hepatitis B during nucleos(t)ide analog therapy |
| title_full | Serum O-glycosylated hepatitis B surface antigen levels in patients with chronic hepatitis B during nucleos(t)ide analog therapy |
| title_fullStr | Serum O-glycosylated hepatitis B surface antigen levels in patients with chronic hepatitis B during nucleos(t)ide analog therapy |
| title_full_unstemmed | Serum O-glycosylated hepatitis B surface antigen levels in patients with chronic hepatitis B during nucleos(t)ide analog therapy |
| title_short | Serum O-glycosylated hepatitis B surface antigen levels in patients with chronic hepatitis B during nucleos(t)ide analog therapy |
| title_sort | serum o glycosylated hepatitis b surface antigen levels in patients with chronic hepatitis b during nucleos t ide analog therapy |
| topic | Hepatitis B virus Hepatitis B surface antigen O-Glycan Pregenomic RNA Virion |
| url | https://doi.org/10.1186/s12876-022-02352-4 |
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