Evidence map›Paper›PMID 32382723›Full record

ArticleJHEP reports : innovation in hepatology2020

TNF-alpha inhibition ameliorates HDV-induced liver damage in a mouse model of acute severe infection.

Carla Usai, Sheila Maestro, Gracian Camps, Cristina Olague, Lester Suárez-Amaran, Africa Vales, Tomas Aragon, Mirja Hommel, Rafael Aldabe, Gloria Gonzalez-Aseguinolaza

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

Article in JHEP reports : innovation in hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

17 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Review
  3. Viral etiologies of acute liver failure.World journal of virology · 2024
    Review
  4. Article
  5. Hepatitis Delta Virus and Hepatocellular Carcinoma.Pathogens (Basel, Switzerland) · 2024
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
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  13. Article
  14. Review
  15. Article
  16. Review
  17. Innovative liver research continues during the current pandemic.JHEP reports : innovation in hepatology · 2020
    Article
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

10 authors at 2 institutions in 1 country.

Carla UsaiGene Therapy and Regulation of Gene Expression Program, CIMA, University of Navarra, Instituto de Investigacion Sanitaria de Navarra, IdisNA, Pamplona, Spain.
Sheila MaestroGene Therapy and Regulation of Gene Expression Program, CIMA, University of Navarra, Instituto de Investigacion Sanitaria de Navarra, IdisNA, Pamplona, Spain.
Gracian CampsGene Therapy and Regulation of Gene Expression Program, CIMA, University of Navarra, Instituto de Investigacion Sanitaria de Navarra, IdisNA, Pamplona, Spain.
Cristina OlagueGene Therapy and Regulation of Gene Expression Program, CIMA, University of Navarra, Instituto de Investigacion Sanitaria de Navarra, IdisNA, Pamplona, Spain.
Lester Suárez-AmaranGene Therapy and Regulation of Gene Expression Program, CIMA, University of Navarra, Instituto de Investigacion Sanitaria de Navarra, IdisNA, Pamplona, Spain.
Africa ValesGene Therapy and Regulation of Gene Expression Program, CIMA, University of Navarra, Instituto de Investigacion Sanitaria de Navarra, IdisNA, Pamplona, Spain.
Tomas AragonGene Therapy and Regulation of Gene Expression Program, CIMA, University of Navarra, Instituto de Investigacion Sanitaria de Navarra, IdisNA, Pamplona, Spain.
Mirja HommelGene Therapy and Regulation of Gene Expression Program, CIMA, University of Navarra, Instituto de Investigacion Sanitaria de Navarra, IdisNA, Pamplona, Spain.
Rafael AldabeGene Therapy and Regulation of Gene Expression Program, CIMA, University of Navarra, Instituto de Investigacion Sanitaria de Navarra, IdisNA, Pamplona, Spain.
Gloria Gonzalez-AseguinolazaGene Therapy and Regulation of Gene Expression Program, CIMA, University of Navarra, Instituto de Investigacion Sanitaria de Navarra, IdisNA, Pamplona, Spain.
Navarre Institute of Health Research · ESUniversidad de Navarra · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsHDV infection induces the most severe form of human viral hepatitis. However, the specific reasons for the severity of the disease remain unknown. Recently, we developed an HDV replication mouse model in which, for the first time, liver damage was detected.

methodsHDV and HBV replication-competent genomes and HDV antigens were delivered to mouse hepatocytes using adeno-associated vectors (AAVs). Aminotransferase elevation, liver histopathology, and hepatocyte death were evaluated and the immune infiltrate was characterized. Liver transcriptomic analysis was performed. Mice deficient for different cellular and molecular components of the immune system, as well as depletion and inhibition studies, were employed to elucidate the causes of HDV-mediated liver damage.

resultsAAV-mediated HBV/HDV coinfection caused hepatocyte necrosis and apoptosis. Activated T lymphocytes, natural killer cells, and proinflammatory macrophages accounted for the majority of the inflammatory infiltrate. However, depletion studies and the use of different knockout mice indicated that neither T cells, natural killer cells nor macrophages were necessary for HDV-induced liver damage. Transcriptomic analysis revealed a strong activation of type I and II interferon (IFN) and tumor necrosis factor (TNF)-α pathways in HBV/HDV-coinfected mice. While the absence of IFN signaling had no effect, the use of a TNF-α antagonist resulted in a significant reduction of HDV-associated liver injury. Furthermore, hepatic expression of HDAg resulted in the induction of severe liver damage, which was T cell- and TNF-α-independent.

conclusionsBoth host (TNF-α) and viral (HDV antigens) factors play a relevant role in HDV-induced liver damage. Importantly, pharmacological inhibition of TNF-α may offer an attractive strategy to aid control of HDV-induced acute liver damage. LAY SUMMARY: Chronic hepatitis delta constitutes the most severe form of viral hepatitis. There is limited data on the mechanism involved in hepatitis delta virus (HDV)-induced liver pathology. Our data indicate that a cytokine (TNF-α) and HDV antigens play a relevant role in HDV-induced liver damage.

Indexed as

AAT, alpha-1-antitrypsinAAV, adeno-associated virusALT, alanine aminotransferaseAntigensAST, aspartate aminotransferasedpi, days post infectionEAlb, albumin enhancerEtanerceptHCC, hepatocellular carcinomaHDVHepatitis BHepatitis Delta virusIFN, interferonIHC, immunohistochemistryIHL, Intrahepatic leukocytesKO, knockoutL-HDAg, large hepatitis D antigenliver injuryMAIT, mucosal-associated invariant T cellsMAVS, mitochondrial antiviral signaling proteinNK, natural killerNKT, natural killer TRag1, recombination activating gene 1S-HDAg, short hepatitis D antigenTg, transgenicTNF, tumor necrosis factorTNF-αULN, upper limit of normal

Identifiers

PMID32382723
PMCPMC7200939
OpenAlexW3011299510

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.