Evidence map›Paper›PMID 29851985›Full record

Trial reportPloS one2018

Reduced ITPase activity and favorable IL28B genetic variant protect against ribavirin-induced anemia in interferon-free regimens.

Aparna Vasanthakumar, Justin W Davis, Manal Abunimeh, Jonas Söderholm, Jiuhong Zha, Emily O Dumas, Daniel E Cohen, Jeffrey F Waring, Martin Lagging

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. 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

9 authors at 2 institutions in 2 countries.

Aparna VasanthakumarAbbVie Inc., North Chicago, Illinois, United States of America.
Justin W DavisAbbVie Inc., North Chicago, Illinois, United States of America.
Manal AbunimehAbbVie Inc., North Chicago, Illinois, United States of America.
Jonas SöderholmAbbVie Inc., North Chicago, Illinois, United States of America.
Jiuhong ZhaAbbVie Inc., North Chicago, Illinois, United States of America.
Emily O DumasAbbVie Inc., North Chicago, Illinois, United States of America.
Daniel E CohenAbbVie Inc., North Chicago, Illinois, United States of America.
Jeffrey F WaringAbbVie Inc., North Chicago, Illinois, United States of America.
Martin LaggingDepartment of Infectious Diseases/Virology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.ORCID 0000-0002-7995-3626
AbbVie (United States) · USUniversity of Gothenburg · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGenetic variants of inosine triphosphatase (ITPA) that confer reduced ITPase activity are associated with protection against ribavirin(RBV)-induced hemolytic anemia in peginterferon(IFN)/RBV-based treatment of hepatitis C virus (HCV). Patients with reduced ITPase activity showed improved treatment efficacy when treated with IFN/RBV. In addition, a genetic polymorphism near the IL28B gene is associated with an improved response to IFN/RBV treatment. RBV has been an important component of IFN-containing regimens, and is currently recommended in combination with several IFN-free regimens for treatment of harder to cure HCV infections.

aimTo evaluate whether genetic variations that reduce ITPase activity impact RBV-induced anemia in IFN-free/RBV regimens.

methodsIn this study, genetic analyses were conducted in the PEARL-IV trial to investigate the effect of activity-reducing ITPA variants as well as IL28B polymorphism on anemia, platelet (PLT) counts, and virologic response in HCV genotype1a-infected patients treated with the direct-acting antiviral (DAA) regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir±RBV.

resultsReduction in ITPase activity and homozygosity for the IL28Brs12979860 CC genotype protected against RBV-induced anemia. In patients receiving RBV, reduced ITPase activity was associated with reduced plasma RBV concentration and higher PLT counts. ITPase activity had no impact on response to DAA treatment, viral kinetics, or baseline IP-10 levels.

conclusionsOur study demonstrates that genetics of ITPA and IL28B may help identify patients protected from RBV-induced anemia when treated with IFN-free regimens. Our work demonstrates for the first time that IL28B genetics may also have an impact on RBV-induced anemia. This may be of particular significance in patients with difficult-to-cure HCV infections, such as patients with decompensated cirrhosis where RBV-containing regimens likely will continue to be recommended.

Indexed as

Polymorphism, GeneticAnemia, HemolyticAntiviral AgentsFemaleHumansInosine TriphosphataseInterferon LambdaInterferonsInterleukinsMalePyrophosphatasesRibavirinAntiviral AgentsInosine TriphosphataseInterferon Lambdainterferon-lambda, humanInterferonsInterleukinsPyrophosphatasesRibavirin

Identifiers

PMID29851985
PMCPMC5979032
OpenAlexW2805550386

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.