Evidence map›Paper›PMID 33055418›Full record

ArticleJCI insight2020

Quadruple mutation GCAC1809-1812TTCT acts as a biomarker in healthy European HBV carriers.

Kai-Henrik Peiffer, Catrina Spengler, Michael Basic, Bingfu Jiang, Lisa Kuhnhenn, Wiebke Obermann, Tobias Zahn, Mirco Glitscher, Alessandro Loglio, Floriana Facchetti and 14 more

Abstract read
In one paragraph

Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis.International journal of molecular sciences · 2023
    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

24 authors.

Kai-Henrik PeifferDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Catrina SpenglerPaul Ehrlich Institute, Division of Virology, Langen, Germany.
Michael BasicDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Bingfu JiangPaul Ehrlich Institute, Division of Virology, Langen, Germany.
Lisa KuhnhennDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Wiebke ObermannInstitute of Pharmaceutical Chemistry, Philipps-University Marburg, Marburg, Germany.
Tobias ZahnPaul Ehrlich Institute, Division of Virology, Langen, Germany.
Mirco GlitscherPaul Ehrlich Institute, Division of Virology, Langen, Germany.
Alessandro LoglioA.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Maggiore Hospital, University of Milan, Milan, Italy.
Floriana FacchettiA.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Maggiore Hospital, University of Milan, Milan, Italy.
Gert CarraPaul Ehrlich Institute, Division of Virology, Langen, Germany.
Alica KubeschDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Johannes VermehrenDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Viola KnopDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Christiana GrafDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Julia DietzDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Fabian FinkelmeierDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Eva HerrmannDepartment of Medicine, Institute of Biostatistics and Mathematical Modeling, J.W. Goethe University, Frankfurt, Germany.
Jonel TrebickaDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Arnold GrünwellerInstitute of Pharmaceutical Chemistry, Philipps-University Marburg, Marburg, Germany.
Stefan ZeuzemDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Christoph SarrazinDepartment of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Pietro LamperticoA.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Maggiore Hospital, University of Milan, Milan, Italy.
Eberhard HildtPaul Ehrlich Institute, Division of Virology, Langen, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many mutation analyses of the HBV genome have been performed in the search for new prognostic markers. However, the Kozak sequence preceding precore was covered only infrequently in these analyses. In this study, the HBV core promoter/precore region was sequenced in serum samples from European inactive HBV carriers. Quadruple mutation GCAC1809-1812TTCT was found with a high prevalence of 42% in the Kozak sequence preceding precore among all HBV genotypes. GCAC1809-1812TTCT was strongly associated with coexistence of basal core promoter (BCP) double mutation A1762T/G1764A and lower HBV DNA levels. In vitro GCAC1809-1812TTCT lead to drastically diminished synthesis of pregenomic RNA (pgRNA), precore mRNA, core, HBsAg, and HBeAg. Calculation of the pgRNA secondary structure suggests a destabilization of the pgRNA structure by A1762T/G1764A that was compensated by GCAC1809-1812TTCT. In 125 patients with HBV-related cirrhosis, GCAC1809-1812TTCT was not detected. While a strong association of GCAC1809-1812TTCT with inactive carrier status was observed, BCP double mutation was strongly correlated with cirrhosis, but this was only observed in absence of GCAC1809-1812TTCT. In conclusion, our data reveal that GCAC1809-1812TTCT is highly prevalent in inactive carriers and acts as a compensatory mutation for BCP double mutation. GCAC1809-1812TTCT seems to be a biomarker of good prognosis in HBV infection.

Indexed as

MutationAdultBiomarkersDNA, ViralEuropeFemaleGenotypeHepatitis BHepatitis B Surface AntigensHepatitis B virusHeterozygoteHumansLiver CirrhosisMaleMiddle AgedPromoter Regions, GeneticBiomarkersDNA, ViralHepatitis B Surface AntigensClinical practiceHepatologyMolecular biologyVirology

Identifiers

PMID33055418
PMCPMC7710305

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Registered trials

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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.