Evidence map›Paper›PMID 18571815›Full record

ArticleHepatology (Baltimore, Md.)2008

Defective hepatitis B virus DNA is not associated with disease status but is reduced by polymerase mutations associated with drug resistance.

Scott Preiss, Margaret Littlejohn, Peter Angus, Alex Thompson, Paul Desmond, Sharon R Lewin, Joe Sasadeusz, Gail Matthews, Gregory J Dore, Tim Shaw and 9 more

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

Article in Hepatology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 25% 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

8 citing papers in PubMed, 28 citations in OpenAlex.

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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

19 authors at 9 institutions in 4 countries.

Scott PreissVictorian Infectious Diseases Reference Laboratories, Research and Molecular Development, North Melbourne, Victoria, Australia.
Margaret Littlejohn
Peter Angus
Alex Thompson
Paul Desmond
Sharon R Lewin
Joe Sasadeusz
Gail Matthews
Gregory J Dore
Tim Shaw
Vitini Sozzi
Lilly Yuen
George Lau
Anna Ayres
Chloe Thio
Anchalee Avihingsanon
Kiat Ruxrungtham
Stephen Locarnini
Peter A Revill
Victorian Infectious Diseases Reference Laboratory · AUHIV Netherlands Australia Thailand Research Collaboration · THJohns Hopkins University · USMonash University · AUNational Centre for Clinical Research on Emerging Drugs · AUSt Vincent's Hospital · AUThe Royal Melbourne Hospital · AUUniversity of Hong Kong · HKUNSW Sydney · AU

Funding

Liver Disease and HIV-HBV Coinfection in the HAART eraR01AI060449 · NIAID · JOHNS HOPKINS UNIVERSITY · PI THIO, CHLOE L · 2004 to 2008
$3.0M
Liver Disease and HIV-HBV co-infection in the HAART eraR56AI060449 · NIAID · JOHNS HOPKINS UNIVERSITY · PI THIO, CHLOE L · 2010 to 2010
$306k
NIAID NIH HHS AI060449NIAID NIH HHS R01 AI060449NIAID NIH HHS R56 AI060449
6 · The paper itself

Abstract

unlabelledDefective hepatitis B virus DNA (dDNA) is reverse-transcribed from spliced hepatitis B virus (HBV) pregenomic messenger RNA (pgRNA) and has been identified in patients with chronic HBV (CH-B). The major 2.2-kb spliced pgRNA encodes a novel HBV gene product, the hepatitis B splice protein (HBSP) via a deletion and frame shift within the polymerase. Although spliced RNA and HBSP expression have been associated with increased HBV DNA levels and liver fibrosis, the role of dDNA in HBV-associated disease is largely undefined. Our aims were to (1) compare the relative proportions of dDNA (% dDNA) in a range of HBV-infected serum samples, including patients with human immunodeficiency virus (HIV)/HBV coinfection and HBV-monoinfected persons with differing severities of liver disease, and (2) determine the effect of mutations associated with drug resistance on defective DNA production. Defective DNA was detected in 90% of persons with CH-B. There was no significant difference in the relative abundance of dDNA between the monoinfected and HIV/HBV-coinfected groups. We also found no association between the % dDNA and alanine aminotransferase, hepatitis B e antigen status, HBV DNA levels, fibrosis levels, compensated or decompensated liver cirrhosis, genotype, or drug treatment. However, the % dDNA was significantly lower in individuals infected with lamivudine-resistant (LMV-R) HBV compared with wild-type HBV (P < 0.0001), indicating that antiviral drug resistance alters the balance between defective and genomic length DNA in circulation. Experiments in vitro using HBV encoding LMV-R mutations confirmed these results.

conclusionOur results identified no association between dDNA and parameters associated with disease status and suggested that the relative abundance of dDNA is largely dependent on the integrity of the HBV polymerase and is unrelated to the severity of liver disease.

Indexed as

Alanine TransaminaseAntiviral AgentsCell Line, TumorDNA, ViralDrug Resistance, ViralFemaleFrameshift MutationGene Products, polGenotypeHepatitis B, ChronicHepatitis B e AntigensHepatitis B virusHIV InfectionsHumansMaleMiddle AgedAlanine TransaminaseAntiviral AgentsDNA, ViralGene Products, polHepatitis B e AntigensP protein, Hepatitis B virus

Identifiers

PMID18571815
PMCPMC2669111
OpenAlexW2065208744

What OpenQuestion holds

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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.