Evidence map›Paper›PMID 27002005›Full record

ArticleGut2017

Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease.

Timothy Hardy, Mujdat Zeybel, Christopher P Day, Christian Dipper, Steven Masson, Stuart McPherson, Elsbeth Henderson, Dina Tiniakos, Steve White, Jeremy French and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Gut, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed
15.7field-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

132 citing papers in PubMed, 211 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Article
  5. Review
  6. Review
  7. PlasmaHepatology forum · 2026
    Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Toxics · 2025
    Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Timothy HardyFibrosis Laboratories, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Mujdat ZeybelSchool of Medicine, Koç University, Istanbul, Turkey.
Christopher P DayFibrosis Laboratories, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Christian DipperDepartment of Gastroenterology and Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Steven MassonDepartment of Gastroenterology and Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Stuart McPhersonDepartment of Gastroenterology and Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Elsbeth HendersonDepartment of Gastroenterology and Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Dina TiniakosFibrosis Laboratories, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Steve WhiteDepartment of Hepatobiliary Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Jeremy FrenchDepartment of Hepatobiliary Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Derek A MannFibrosis Laboratories, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Quentin M AnsteeFibrosis Laboratories, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Jelena MannFibrosis Laboratories, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Newcastle University · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GBKoç University · TR

Funding

Epigenetic Regulation of Alcoholic Liver FibrosisU01AA018663 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KISSELEVA, TATIANA, MANN, DEREK · 2010 to 2019
$3.7M
Medical Research Council L016354Medical Research Council MR/K001949/1Medical Research Council MR/L002094/1NIAAA NIH HHS U01 AA018663
6 · The paper itself

Abstract

objectiveLiver biopsy is currently the most reliable way of evaluating liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Its inherent risks limit its widespread use. Differential liver DNA methylation of peroxisome proliferator-activated receptor gamma (PPARγ) gene promoter has recently been shown to stratify patients in terms of fibrosis severity but requires access to liver tissue. The aim of this study was to assess whether DNA methylation of circulating DNA could be detected in human plasma and potentially used to stratify liver fibrosis severity in patients with NAFLD.

designPatients with biopsy-proven NAFLD and age-matched controls were recruited from the liver and gastroenterology clinics at the Newcastle upon Tyne Hospitals NHS Foundation Trust. Plasma cell-free circulating DNA methylation of PPARγ was quantitatively assessed by pyrosequencing. Liver DNA methylation was quantitatively assessed by pyrosequencing NAFLD explant tissue, subjected to laser capture microdissection (LCM). Patients with alcoholic liver disease (ALD) were also subjected to plasma DNA and LCM pyrosequencing.

results26 patients with biopsy-proven NAFLD were included. Quantitative plasma DNA methylation of PPARγ stratified patients into mild (Kleiner 1-2) and severe (Kleiner 3-4) fibrosis (CpG1: 63% vs 86%, p<0.05; CpG2: 51% vs 65% p>0.05). Hypermethylation at the PPARγ promoter of plasma DNA correlated with changes in hepatocellular rather than myofibroblast DNA methylation. Similar results were demonstrated in patients with ALD cirrhosis.

conclusionsDifferential DNA methylation at the PPARγ promoter can be detected within the pool of cell-free DNA of human plasma. With further validation, plasma DNA methylation of PPARγ could potentially be used to non-invasively stratify liver fibrosis severity in patients with NAFLD. Plasma DNA methylation signatures reflect the molecular pathology associated with fibrotic liver disease.

Indexed as

DNA MethylationSeverity of Illness IndexCase-Control StudiesFemaleGenetic MarkersHigh-Throughput Nucleotide SequencingHumansLiver CirrhosisMaleMiddle AgedNon-alcoholic Fatty Liver DiseasePPAR gammaGenetic MarkersPPAR gammaHEPATIC FIBROSISMOLECULAR GENETICSMOLECULAR PATHOLOGYNONALCOHOLIC STEATOHEPATITISPPAR GAMMA

Identifiers

PMID27002005
PMCPMC5031527
OpenAlexW2306606423

What Socratic 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 Socratic graph.