ArticleJournal of hepatology2017
Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA.
Article in Journal of hepatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01088009 (A Prospective, Randomised, Open-label, Multi-centre Study to Compare Three Chronic Hepatitis B), which is not on this map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Prospective, Randomised, Open-label, Multi-centre Study to Compare Three Chronic Hepatitis B (CHB) Treatment Strategies Over a 2year Period in Chinese HBeAg Positive CHB Patients
Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- Structure-guided discovery and engineering of miniature CRISPR-Cas12m for epigenome editing.Nature structural & molecular biology · 2026Article
- Occult hepatitis B virus infection.Nature reviews. Gastroenterology & hepatology · 2026Review
- Understanding Basic Concepts of Viral Quasispecies: From Evolutionary Dynamics to Clinical Relevance.Pathogens (Basel, Switzerland) · 2026Review
- Article
- Dual defects in HBsAg antigenicity and secretion caused by the C138R mutation in the S gene trigger occult hepatitis B virus infection.Journal of translational medicine · 2025Article
- Characterization of genetic mutations in hepatitis B virus isolated from HBsAg+/HBcAb+/HBsAb-/HBV DNA + Japanese blood donors.Scientific reports · 2025Article
- Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway.Open life sciences · 2025Article
- Transfusion-transmitted occult hepatitis B virus infection: current understanding, challenges, and its implication in blood safety.Frontiers in immunology · 2025Review
- Comparison of Clinical Manifestations and Related Factors of Hepatocellular Carcinoma with Chronic Hepatitis B.International journal of general medicine · 2024Article
- Host immunity and HBV S gene mutation in HBsAg-negative HBV-infected patients.Frontiers in immunology · 2023Article
- Small Hepatitis B Virus Surface Antigen Promotes Hepatic Gluconeogenesis via Enhancing Glucagon/cAMP/Protein Kinase A/CREB Signaling.Journal of virology · 2022Article
- Article
- In vitro investigation of HBV clinical isolates from Chinese patients reveals that genotype C isolates possess higher infectivity than genotype B isolates.Virologica Sinica · 2022Article
- 5' preS1 Mutations To Prevent Large Envelope Protein Expression from Hepatitis B Virus Genotype A or Genotype D Markedly Increase Polymerase-Envelope Fusion Protein.Journal of virology · 2022Article
- Analysis of S gene characteristic sequences and changes in properties of protein expression in HBV ASCs with low-level HBsAg.Frontiers in medicine · 2022Article
- The Relationship Between Collagen Proportionate Area and Hepatitis B Surface Antigen Levels in E Antigen Positive Hepatitis B Cirrhosis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Article
- Hepatitis B Virus Pregenomic RNA Reflecting Viral Replication in Distal Non-tumor Tissues as a Determinant of the Stemness and Recurrence of Hepatocellular Carcinoma.Frontiers in microbiology · 2022Article
- Research Progress on the Mechanism of Persistent Low-Level HBsAg Expression in the Serum of Patients with Chronic HBV Infection.Journal of immunology research · 2022Review
- In silico analysis of mutations associated with occult hepatitis B virus (HBV) infection in South Africa.Archives of virology · 2021Article
- Drug-resistant and immune-escape hepatitis B virus mutants, occult hepatitis B infection and coinfections in public hospital patients from Argentina.Virus genes · 2021Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsAs important virological markers, serum hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels show large fluctuations among chronic hepatitis B patients. The aim of this study was to reveal the potential impact and mechanisms of amino acid substitutions in small hepatitis B surface proteins (SHBs) on serum HBsAg and HBV DNA levels.
methodsSerum samples from 230 untreated chronic hepatitis B patients with genotype C HBV were analyzed in terms of HBV DNA levels, serological markers of HBV infection and SHBs sequences. In vitro functional analysis of the identified SHBs mutants was performed.
resultsAmong 230 SHBs sequences, there were 39 (16.96%) sequences with no mutation detected (wild-type) and 191 (83.04%) with single or multiple mutations. SHBs consist of 226 amino acids, of which 104 (46.02%) had mutations in our study. Some mutations (e.g., sE2G, sL21S, sR24K, sT47A/K, sC69stop (sC69∗), sL95W, sL98V, and sG145R) negatively correlated with serum HBsAg levels. HBsAg and HBV DNA levels from this group of patients had a positive correlation (r=0.61, p<0.001). In vitro analysis showed that these mutations reduced extracellular HBsAg and HBV DNA levels by restricting virion secretion and antibody binding capacity. Virion secretion could be rescued for sE2G, sC69∗, and sG145R by co-expression of wild-type HBsAg.
conclusionThe serum HBsAg levels were lower in untreated CHB patients with novel SHBs mutations outside the major antigenic region than those without mutations. Underlying mechanisms include impairment of virion secretion and lower binding affinity to antibodies used for HBsAg measurements. LAY SUMMARY: The hepatitis B surface antigen (HBsAg) is a major viral protein of the hepatitis B virus (HBV) secreted into patient blood serum and its quantification value serves as an important marker for the evaluation of chronic HBV infection and antiviral response. We found a few new amino acid substitutions in HBsAg associated with lower serum HBsAg and HBV DNA levels. These different substitutions might impair virion secretion, change the ability of HBsAg to bind to antibodies, or impact HBV replication. These could all result in decreased detectable levels of serum HBsAg. The factors affecting circulating HBsAg level and HBsAg detection are varied and caution is needed when interpreting clinical significance of serum HBsAg levels. Clinical trial number: NCT01088009.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.