Evidence map›Paper›PMID 25772035›Full record

ArticleJournal of hepatology2015

Liver-directed gene therapy of chronic hepadnavirus infection using interferon alpha tethered to apolipoprotein A-I.

Pedro Berraondo, Marianna Di Scala, Kyle Korolowicz, Linta M Thampi, Itziar Otano, Lester Suarez, Jessica Fioravanti, Fernando Aranda, Nuria Ardaiz, Junming Yang and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. EfficientJHEP reports : innovation in hepatology · 2020
    Article
  9. Inhibition of eIF2BioMed research international · 2020
    Article
  10. Review
  11. Review
  12. In Situ Liver Expression of HBsAg/CD3-Bispecific Antibodies for HBV Immunotherapy.Molecular therapy. Methods & clinical development · 2017
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
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

16 authors at 3 institutions in 2 countries.

Pedro BerraondoDivision of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain. Electronic address: pberraondol@unav.es.
Marianna Di ScalaDivision of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain.
Kyle KorolowiczDepartment of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, USA.
Linta M ThampiDepartment of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, USA.
Itziar OtanoDivision of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain.
Lester SuarezDivision of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain.
Jessica FioravantiDivision of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain.
Fernando ArandaDivision of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain.
Nuria ArdaizDivision of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain.
Junming YangDepartment of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, USA.
Bhaskar V KallakuryDepartment of Pathology, Georgetown University Medical Center, Washington, DC, USA.
Robin D TuckerDivision of Comparative Medicine, Georgetown University Medical Center, Washington, DC, USA.
Marcos VasquezDivision of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain.
Stephan MenneDepartment of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, USA.
Jesús PrietoDivision of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain.
Gloria González-AseguinolazaDivision of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain.
Universidad de Navarra · ESGeorgetown University · USGeorgetown University Medical Center · US

Funding

NIAID NIH HHS HHSN272201000011IPHS HHS HHSN27200002
6 · The paper itself

Abstract

BACKGROUND &

aimsCurrent hepatitis B virus (HBV) management is challenging as treatment with nucleos(t)ide analogues needs to be maintained indefinitely and because interferon (IFN)-α therapy is associated with considerable toxicity. Previously, we showed that linking IFNα to apolipoprotein A-I generates a molecule (IA) with distinct antiviral and immunostimulatory activities which lacks the hematological toxicity of IFNα.

methodsHere, we analyse the antiviral potential of an adeno-associated vector encoding IFNα fused to apolipoprotein A-I (AAV-IA) in comparison to a vector encoding only IFNα (AAV-IFN) in two animal models of chronic hepadnavirus infection.

resultsIn HBV transgenic mice, we found that both vectors induced marked reductions in serum and liver HBV DNA and in hepatic HBV RNA but AAV-IFN caused lethal pancytopenia. Woodchucks with chronic hepatitis virus (WHV) infection that were treated by intrahepatic injection of vectors encoding the woodchuck sequences (AAV-wIFN or AAV-wIA), experienced only a slight reduction of viremia which was associated with hematological toxicity and high mortality when using AAV-wIFN, while AAV-wIA was well tolerated. However, when we tested AAV-wIA or a control vector encoding woodchuck apolipoprotein A-I (AAV-wApo) in combination with entecavir, we found that AAV-wApo-treated animals exhibited an immediate rebound of viral load upon entecavir withdrawal while, in AAV-wIA-treated woodchucks, viremia and antigenemia remained at low levels for several weeks following entecavir interruption.

conclusionsTreatment with AAV-IA is safe and elicits antiviral effects in animal models with difficult to treat chronic hepadnavirus infection. AAV-IA in combination with nucleos(t)ide analogues represents a promising approach for the treatment of HBV infection in highly viremic patients.

Indexed as

AnimalsAntiviral AgentsApolipoprotein A-IDisease Models, AnimalDNA, ViralFemaleGenetic TherapyGenetic VectorsHepadnaviridaeHepatitis B, ChronicInterferon-alphaLiverMiceMice, Inbred C57BLMice, TransgenicAntiviral AgentsApolipoprotein A-IDNA, ViralInterferon-alphaAntiviralsChronic hepatitis BGenetic transferIFN-α hematological toxicityWoodchuck

Identifiers

PMID25772035
PMCPMC4508219
OpenAlexW2130850500

What OpenQuestion holds

Textmetadata
LicenceTDM
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.