Evidence map›Paper›PMID 40645766›Full record

ArticleGut2025

Therapeutic inhibition of HBsAg and HBV cccDNA through a novel phased combination treatment: glycine and interferon-α.

Caorui Lin, Ying Huang, Ning Ran, Jie Liu, Linjie Luo, Xin Zhang, Xiaosang Zheng, Zhen Xun, Siyi Xu, Can Liu and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. [High expression of low-risk hpv in nasal inverted papilloma and its response to interferon therapy].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Caorui Lin *Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China ouqishui@fjmu.edu.cn caoruilin@email.sdu.edu.cn shiqingfeng@sdu.edu.cn maohaiting@sdu.edu.cn.ORCID 0000-0002-8680-3159
Ying Huang *Department of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Fujian Clinical Research Center for Laboratory Medicine of Immunology, Gene Diagnosis Research Center, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Ning Ran *Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.ORCID 0009-0007-9149-5940
Jie LiuDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Linjie LuoDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Fujian Clinical Research Center for Laboratory Medicine of Immunology, Gene Diagnosis Research Center, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Xin ZhangDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Fujian Clinical Research Center for Laboratory Medicine of Immunology, Gene Diagnosis Research Center, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Xiaosang ZhengDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Fujian Clinical Research Center for Laboratory Medicine of Immunology, Gene Diagnosis Research Center, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Zhen XunDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Fujian Clinical Research Center for Laboratory Medicine of Immunology, Gene Diagnosis Research Center, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Siyi XuDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Fujian Clinical Research Center for Laboratory Medicine of Immunology, Gene Diagnosis Research Center, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Can LiuDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Fujian Clinical Research Center for Laboratory Medicine of Immunology, Gene Diagnosis Research Center, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Xiaohong KongShandong University Orthopedic Research Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Shiqing FengShandong University Orthopedic Research Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China ouqishui@fjmu.edu.cn caoruilin@email.sdu.edu.cn shiqingfeng@sdu.edu.cn maohaiting@sdu.edu.cn.
Haiting MaoDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China ouqishui@fjmu.edu.cn caoruilin@email.sdu.edu.cn shiqingfeng@sdu.edu.cn maohaiting@sdu.edu.cn.
Qishui OuDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Fujian Clinical Research Center for Laboratory Medicine of Immunology, Gene Diagnosis Research Center, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China ouqishui@fjmu.edu.cn caoruilin@email.sdu.edu.cn shiqingfeng@sdu.edu.cn maohaiting@sdu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe elimination of HBV covalently closed circular DNA (cccDNA) remains a critical hurdle for chronic hepatitis B (CHB) management.

objectiveIn this investigation, we examined the efficacy of glycine administration and its potential enhancement in interferon-α (IFN-α) antiviral efficacy to stimulate hepatocyte proliferation to mitigate cccDNA levels.

designThe study cohort comprised 89 healthy individuals and 496 HBV-infected patients, with subgroups of 30 and 42 participants receiving randomised nucleos(t)ide analogue (NA) and PegIFN-α treatments, respectively. Glycine concentrations were quantified via liquid chromatography‒tandem mass spectrometry, and its diagnostic potential was assessed via receiver operating characteristic curve analysis. The therapeutic impact of glycine was evaluated in various HBV-infected cell lines and murine models via various methodologies including transcriptomic sequencing, metabolomics sequencing, flow cytometry, immunofluorescence and in situ hybridisation.

resultsElevated serum glycine levels with a robust positive correlation with serum alanine aminotransferase levels (R=0.7650) were observed in HBV-infected patients relative to healthy controls. The area under the curve for differentiating patients with HBeAg-expressing CHB from healthy controls was 0.9701. Glycine supplementation diminished HBV cccDNA levels by approximately 50% by promoting hepatocyte proliferation. Glycine is metabolised into a one-carbon unit, activating mTORC1 signalling via glycine transporter-1. Furthermore, glycine ameliorates hepatic inflammation by inhibiting the nuclear factor-kappa B signalling pathway through glycine receptors. Combination therapy with IFN-α effectively suppressed HBV replication, achieving a 60% reduction in HBsAg levels and sustained viral suppression in mice.

conclusionGlycine has the potential to reduce HBV cccDNA levels by stimulating hepatocyte proliferation. The phased administration of glycine and IFN-α significantly enhances its therapeutic efficacy. These findings suggest a novel and promising strategy for the treatment of CHB.

Indexed as

Antiviral AgentsDNA, CircularDNA, ViralGlycineHepatitis B, ChronicHepatitis B Surface AntigensHepatitis B virusInterferon-alphaAdultAnimalsCell ProliferationDrug Therapy, CombinationFemaleHepatocytesHumansMaleAntiviral AgentsDNA, CircularDNA, ViralGlycineHepatitis B Surface AntigensInterferon-alphaANTIVIRAL THERAPYCHRONIC VIRAL HEPATITISDIAGNOSTIC VIROLOGYHEPATITIS BNUTRITION

Identifiers

PMID40645766
PMCPMC12703313

What OpenQuestion holds

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Registered trials

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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.