Evidence map›Paper›PMID 27222534›Full record

ArticleGut2016

In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome.

Daniel Todt, Anett Gisa, Aleksandar Radonic, Andreas Nitsche, Patrick Behrendt, Pothakamuri Venkata Suneetha, Sven Pischke, Birgit Bremer, Richard J P Brown, Michael P Manns and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 1 pooled it
12.3field-weighted citation impact, top 1% 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

106 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.

  1. Pooled it
  2. Extrahepatic Replication and Genomic Signatures of the Hepatitis E Virus in the Kidney.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Trial
  3. Trial
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Update on Hepatitis E Virus Infection 2025: Insights From an International Symposium.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  16. Article
  17. Differential miRNA signatures in Hepatitis E Virus Infection: Insights into acute, chronic, and pregnancy-related outcomes.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025
    Review
  18. Mycophenolic acid treatment drives the emergence of novel SARS-CoV-2 variants.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Hepatitis E virus: from innate sensing to adaptive immune responses.Nature reviews. Gastroenterology & hepatology · 2024
    Review

46 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 1 country.

Daniel TodtInstitute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Anett GisaDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Aleksandar RadonicDivision of Highly Pathogenic Viruses, Robert-Koch-Institut, Centre for Biological Threats and Special Pathogens, Berlin, Germany.
Andreas NitscheDivision of Highly Pathogenic Viruses, Robert-Koch-Institut, Centre for Biological Threats and Special Pathogens, Berlin, Germany.
Patrick BehrendtInstitute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Pothakamuri Venkata SuneethaDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Sven PischkeDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany First Medical Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Birgit BremerDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Richard J P BrownInstitute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Michael P MannsDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany German Center for Infectious Disease Research (DZIF), Partnersite Hannover-Braunschweig, Germany.
Markus CornbergDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany German Center for Infectious Disease Research (DZIF), Partnersite Hannover-Braunschweig, Germany.
C Thomas BockDivision of Viral Gastroenteritis, Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert-Koch-Institut, Berlin, Germany.
Eike SteinmannInstitute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Heiner WedemeyerDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany German Center for Infectious Disease Research (DZIF), Partnersite Hannover-Braunschweig, Germany.
Medizinische Hochschule Hannover · DERobert Koch Institute · DECenter for Experimental and Clinical Infection Research · DEHelmholtz Centre for Infection Research · DEUniversität Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveHepatitis E virus (HEV) infection can take chronic courses in immunocompromised patients potentially leading to liver cirrhosis and liver failure. Ribavirin (RBV) is currently the only treatment option for many patients, but treatment failure can occur which has been associated with the appearance of a distinct HEV polymerase mutant (G1634R). Here, we performed a detailed analysis of HEV viral intrahost evolution during chronic hepatitis E infections.

designIllumina deep sequencing was performed for the detection of intrahost variation in the HEV genome of chronically infected patients. Novel polymerase mutants were investigated in vitro using state-of-the-art HEV cell culture models.

resultsTogether, these data revealed that (1) viral diversity differed markedly between patients but did not show major intraindividual short-term variations in untreated patients with chronic hepatitis E, (2) RBV therapy was associated with an increase in viral heterogeneity which was reversible when treatment was stopped, (3) the G1634R mutant was detectable as a minor population prior to therapy in patients who subsequently failed to achieve a sustained virological response to RBV therapy and (4) in addition to G1634R further dominant variants in the polymerase region emerged, impacting HEV replication efficiency in vitro.

conclusionsIn summary, this first investigation of intrahost HEV population evolution indicates that RBV causes HEV mutagenesis in treated patients and that an emergence of distinct mutants within the viral population occurs during RBV therapy. We also suggest that next-generation sequencing could be useful to guide personalised antiviral strategies.

Indexed as

Hepatitis EHepatitis E virusMutagenesisRibavirinAdolescentAdultAgedAntiviral AgentsChronic DiseaseDrug MonitoringFemaleGenetic HeterogeneityGenome, ViralHumansMaleMiddle AgedAntiviral AgentsRibavirinANTIVIRAL THERAPYCHRONIC HEPATITISHEPATITIS E

Identifiers

PMID27222534
PMCPMC5036239
OpenAlexW2405561744

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.