Evidence map›Paper›PMID 34105780›Full record

ArticleHepatology (Baltimore, Md.)2021

Transcriptomics Identify Thrombospondin-2 as a Biomarker for NASH and Advanced Liver Fibrosis.

Kazuhiro Kozumi, Takahiro Kodama, Hiroki Murai, Sadatsugu Sakane, Olivier Govaere, Simon Cockell, Daisuke Motooka, Naruyasu Kakita, Yukinori Yamada, Yasuteru Kondo and 10 more

Open access · hybridAbstract readMulticenter Study
In one paragraph

Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 4 pooled it
19.4field-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

89 citing papers in PubMed, 4 syntheses or guidelines pooled it, 165 citations in OpenAlex.

  1. Pooled it
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  5. Article
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  7. Review
  8. Gene-Based Clustering Identifies QSOX1 and IL1RAP as Biomarkers of Metabolic Dysfunction-Associated Steatotic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
  9. Intrahepatic Platelets Orchestrate Microenvironmental Remodelling and Cellular Crosstalk in Liver Fibrosis.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Review
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  19. F13A1-Mediated Macrophage Activation Promotes MASH Progression via the PKM2/HIF1A Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 2 countries.

Kazuhiro Kozumi *Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Takahiro Kodama *Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.ORCID 0000-0002-6250-1324
Hiroki MuraiDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Sadatsugu SakaneDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Olivier GovaereTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Simon CockellTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Daisuke MotookaGenome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Naruyasu KakitaDepartment of Gastroenterology and Hepatology, Kaizuka City Hospital, Osaka, Japan.
Yukinori YamadaDepartment of Gastroenterology and Hepatology, Kaizuka City Hospital, Osaka, Japan.
Yasuteru KondoDepartment of Hepatology, Sendai Kousei Hospital, Sendai, Japan.ORCID 0000-0001-5935-4346
Yuki TahataDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Ryoko YamadaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Hayato HikitaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Ryotaro SakamoriDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.ORCID 0000-0002-1580-607X
Yoshihiro KamadaDepartment of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Ann K DalyTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Quentin M AnsteeTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom.ORCID 0000-0002-9518-0088
Tomohide TatsumiDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Eiichi MoriiDepartment of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.
Tetsuo TakeharaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
The University of Osaka · JPNewcastle University · GBTakarazuka City Hospital · JPNational Health Service · GBOsaka City University · JPSendai Kousei Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsNAFLD is the most common liver disease worldwide. NASH, the progressive form of NAFLD, and advanced fibrosis are associated with poor outcomes. We searched for their noninvasive biomarkers. APPROACH AND

resultsGlobal RNA sequencing of liver tissue from 98 patients with biopsy-proven NAFLD was performed. Unsupervised hierarchical clustering well distinguished NASH from nonalcoholic fatty liver (NAFL), and patients with NASH exhibited molecular abnormalities reflecting their pathological features. Transcriptomic analysis identified proteins up-regulated in NASH and/or advanced fibrosis (stage F3-F4), including matricellular glycoprotein thrombospondin-2 (TSP-2), encoded by the thrombospondin 2 (THBS2) gene. The intrahepatic THBS2 expression level showed the highest areas under the receiver operating characteristic curves (AUROCs) of 0.915 and 0.957 for diagnosing NASH and advanced fibrosis, respectively. THBS2 positively correlated with inflammation and ballooning according to NAFLD activity score, serum aspartate aminotransferase and hyaluronic acid (HA) levels, and NAFLD Fibrosis Score (NFS). THBS2 was associated with extracellular matrix and collagen biosynthesis, platelet activation, caspase-mediated cleavage of cytoskeletal proteins, and immune cell infiltration. Serum TSP-2 expression was measured in 213 patients with biopsy-proven NAFLD, was significantly higher in NASH than in NAFL, and increased parallel to fibrosis stage. The AUROCs for predicting NASH and advanced fibrosis were 0.776 and 0.856, respectively, which were comparable to Fibrosis-4 index, serum HA level, and NFS in advanced fibrosis diagnosis. Serum TSP-2 level and platelet count were independent predictors of NASH and advanced fibrosis. Serum TSP-2 levels could stratify patients with NAFLD according to the risk of hepatic complications, including liver cancer and decompensated cirrhotic events.

conclusionsTSP-2 may be a useful biomarker for NASH and advanced fibrosis diagnosis in patients with NAFLD.

Indexed as

AdultAgedArea Under CurveAspartate AminotransferasesBiomarkersBiopsyFemaleFollow-Up StudiesGene Expression ProfilingHumansHyaluronic AcidLiverLiver CirrhosisMaleMiddle AgedNon-alcoholic Fatty Liver DiseaseAspartate AminotransferasesBiomarkersHyaluronic AcidThrombospondin 2Thrombospondins

Identifiers

PMID34105780
PMCPMC8596693
OpenAlexW3160822742

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.