Evidence map›Paper›PMID 27789659›Full record

ArticleGut2018

Induction of IFN-λ3 as an additional effect of nucleotide, not nucleoside, analogues: a new potential target for HBV infection.

Kazumoto Murata, Mai Asano, Akihiro Matsumoto, Masaya Sugiyama, Nao Nishida, Eiji Tanaka, Taisuke Inoue, Minoru Sakamoto, Nobuyuki Enomoto, Takayoshi Shirasaki and 9 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 8 pooled it
7.2field-weighted citation impact, top 2% of its field
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

97 citing papers in PubMed, 8 syntheses or guidelines pooled it, 187 citations in OpenAlex.

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  17. [Effect of switching from entecavir to tenofovir amibufenamide on HBsAg levels in patients with chronic hepatitis B: a 96-week real-world study].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Article
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37 more citing papers are in PubMed but not listed here.

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

19 authors at 7 institutions in 2 countries.

Kazumoto MurataThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
Mai AsanoThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
Akihiro MatsumotoDepartment of Medicine, Shinshu University of Medicine, Matsumoto, Japan.
Masaya SugiyamaThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
Nao NishidaThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
Eiji TanakaDepartment of Medicine, Shinshu University of Medicine, Matsumoto, Japan.
Taisuke InoueFirst Department of Medicine, University of Yamanashi, Chuo, Japan.
Minoru SakamotoFirst Department of Medicine, University of Yamanashi, Chuo, Japan.
Nobuyuki EnomotoFirst Department of Medicine, University of Yamanashi, Chuo, Japan.
Takayoshi ShirasakiDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Masao HondaDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Shuichi KanekoDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Hiroyuki GatanagaAIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
Shinichi OkaAIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
Yuki I KawamuraDepartment of Gastroenterology, The Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Japan.
Taeko DohiDepartment of Gastroenterology, The Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Japan.
Yasutaka ShunoDivision of Colorectal Surgery, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.
Hideaki YanoDivision of Colorectal Surgery, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.
Masashi MizokamiThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
Center for Global Health · USNational Center for Global Health and Medicine · JPKanazawa University · JPUniversity of Yamanashi · JPNagoya City University · JPShinshu University · JPShinshu University Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe clinical significance of polymorphisms in the interleukin-28B gene encoding interferon (IFN)-λ3, which has antiviral effects, is known in chronic HCV but not in HBV infection. Thus, we measured IFN-λ3 levels in patients with HBV and investigated its clinical significance and association with nucleos(t)ide (NUC) analogue administration.

designSerum IFN-λ3 level was measured in 254 patients with HBV with varying clinical conditions using our own high sensitivity method. The resulting values were compared with various clinical variables. In addition, cell lines originating from various organs were cultured with NUCs, and the production of IFN-λ3 was evaluated.

resultsHigher serum IFN-λ3 levels were detected in the patients treated with nucleotide analogues (adefovir or tenofovir) compared with those treated with nucleoside analogues (lamivudine or entecavir). There were no other differences in the clinical background between the two groups. A rise in the serum IFN-λ3 levels was observed during additional administration of the nucleotide analogues. In vitro experiments showed that the nucleotide analogues directly and dose-dependently induced IFN-λ3 production only in colon cancer cells. Furthermore, the supernatant from cultured adefovir-treated colon cancer cells significantly induced IFN-stimulated genes (ISGs) and inhibited hepatitis B surface antigen (HBsAg) production in hepatoma cells, as compared with the supernatant from entecavir-treated cells.

conclusionsWe discovered that the nucleotide analogues show an additional pharmacological effect by inducing IFN-λ3 production, which further induces ISGs and results in a reduction of HBsAg production. These findings provide novel insights for HBV treatment and suggest IFN-λ3 induction as a possible target.

Indexed as

AdenineAdultAgedAged, 80 and overAntiviral AgentsAsymptomatic InfectionsCarcinoma, HepatocellularCulture Media, ConditionedDNA, ViralFemaleGene ExpressionGenotypeGuanineHepatitis B, ChronicHepatitis B Surface AntigensHepatitis B virusadefovirAdenineAntiviral AgentsCulture Media, ConditionedDNA, ViralentecavirGuanineHepatitis B Surface AntigensInterferon Lambdainterferon-lambda, humanInterferonsInterleukinsLamivudineOrganophosphonatesRecombinant ProteinsTenofovirANTIVIRAL THERAPYCHRONIC VIRAL HEPATITISINTERFERON

Identifiers

PMID27789659
PMCPMC5868296
OpenAlexW2544680672

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.