Evidence map›Paper›PMID 35073596›Full record

ArticleHepatology (Baltimore, Md.)2022

Quantified integrated hepatitis B virus is related to viral activity in patients with chronic hepatitis B.

Robin Erken, Vladimir Loukachov, Karel van Dort, Anne van den Hurk, R Bart Takkenberg, Anniki de Niet, Louis Jansen, Sophie Willemse, Henk Reesink, Neeltje Kootstra

Open access · hybridAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. [Clinical significance and occurrence mechanism of hepatitis B virus DNA integration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. [Expert recommendations on screening, testing and management for hepatitis B virus infection in adults].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024
    Article
  12. Review
  13. Article
  14. [Research progress on the effect of hepatitis B virus DNA integration on antiviral therapy].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024
    Review
  15. [Predictive factors for HBsAg-negative seroconversion in chronic hepatitis B after antiviral therapy].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024
    Review
  16. [Research progress on the role of hepatitis B virus DNA integration in chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024
    Review
  17. Article
  18. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022).Journal of clinical and translational hepatology · 2023
    Article
  19. Phenolic Compounds inMolecules (Basel, Switzerland) · 2023
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Robin ErkenDepartment of Experimental Immunology, Amsterdam UMC, location AMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, the Netherlands.
Vladimir LoukachovDepartment of Experimental Immunology, Amsterdam UMC, location AMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, the Netherlands.
Karel van DortDepartment of Experimental Immunology, Amsterdam UMC, location AMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, the Netherlands.
Anne van den HurkDepartment of Experimental Immunology, Amsterdam UMC, location AMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, the Netherlands.
R Bart TakkenbergDepartment of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, location AMC, Amsterdam, the Netherlands.
Anniki de NietDepartment of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, location AMC, Amsterdam, the Netherlands.
Louis JansenDepartment of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, location AMC, Amsterdam, the Netherlands.
Sophie WillemseDepartment of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, location AMC, Amsterdam, the Netherlands.
Henk ReesinkDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
Neeltje KootstraDepartment of Experimental Immunology, Amsterdam UMC, location AMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, the Netherlands.
University of Amsterdam · NLAmsterdam University Medical Centers · NLInstitute of Infection and Immunity · CAAmsterdam Neuroscience · NLLeiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsHBV can integrate in the host genome of the hepatocyte and recent findings suggest that integrated HBV contributes to the persistent production of viral proteins. Here, we quantified the levels of integrated HBV in patients with chronic hepatitis B (CHB) and analyzed the relation between HBV integration, virological activity (plasma HBV DNA and HBsAg levels), and clinical outcomes. APPROACH AND

resultsWe developed and validated a multistep Arthrobacter luteus (Alu)-PCR that specifically amplifies integrated HBV and RT-Alu-PCR detecting mRNA transcripts derived from integrated HBV. Pretreatment liver biopsy samples and baseline characteristics of 124 patients with CHB either treated for 48 weeks with pegylated interferon plus adefovir or tenofovir or receiving no treatment were available for analysis. Integrated HBV sequences containing open reading frame S and X (but not C) and S and X mRNA transcripts derived from integrated HBV could be detected and quantified in liver biopsies. Integrated HBV levels correlated with HBV DNA, HBsAg, alanine aminotransferase plasma levels, and the liver histology activity index but not to levels of intrahepatic covalently closed circular DNA (cccDNA), plasma pregenomic RNA, or hepatitis B core-related antigen. Multivariable logistic regression analysis showed that lower baseline HBV integration levels were independently associated with HBsAg loss (functional cure) within 5 years follow-up.

conclusionsIntegrated HBV levels are strongly correlated with surrogate markers for virological activity but not to cccDNA levels and are predictive for HBsAg loss. Our data suggest that integrated HBV is closely related to HBV replication and may therefore be an important tool in the evaluation and development of treatment modalities aiming to cure CHB.

Indexed as

Hepatitis B, ChronicHepatitis B virusAntiviral AgentsDNA, CircularDNA, ViralHepatitis B Core AntigensHepatitis B e AntigensHepatitis B Surface AntigensHumansLiverRNA, MessengerAntiviral AgentsDNA, CircularDNA, ViralHepatitis B Core AntigensHepatitis B e AntigensHepatitis B Surface AntigensRNA, Messenger

Identifiers

PMID35073596
PMCPMC9305117
OpenAlexW4206970776

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.