Evidence map›Paper›PMID 40085416›Full record

ArticleHepatology international2025

Efficacy of measuring natural killer-activating receptor ligands to predict the pathogenesis of metabolic dysfunction-associated steatotic liver disease.

Jun Arai, Akinori Okumura, Satoshi Kimoto, Kazumasa Sakamoto, Tomoya Kitada, Rena Kitano, Tadahisa Inoue, Sayaka Nishimura, Noriko Inden, Yukiko Muraki and 2 more

Abstract read
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Article in Hepatology international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
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  4. 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

12 authors.

Jun AraiDepartment of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan. arai.jun.657@mail.aichi-med-u.ac.jp.ORCID http://orcid.org/0000-0001-5902-6246
Akinori OkumuraDepartment of Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi, Japan.
Satoshi KimotoDepartment of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Kazumasa SakamotoDepartment of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Tomoya KitadaDepartment of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Rena KitanoDepartment of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Tadahisa InoueDepartment of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Sayaka NishimuraDepartment of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Noriko IndenDepartment of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Yukiko MurakiDepartment of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Naoya KatoDepartment of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kiyoaki ItoDepartment of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.

Funding

Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology 23K06657Japan Agency for Medical Research and Development JP22fk0310502
6 · The paper itself

Abstract

objectiveThe proportion of non-B/non-C hepatocellular carcinoma cases is increasing, and the principal cause is metabolic dysfunction-associated steatotic liver disease (MASLD). The degree of intrahepatic natural killer (NK) cell infiltration has been reported to correlate with MASLD progression. However, reports on MASLD are limited. We aimed to investigate the involvement of NK cell-activating receptor ligands in MASLD pathogenesis.

methodsThis study cohort comprised 69 patients with biopsy-proven MASLD treated between 2012 and 2018 at our institute. The concentrations of major histocompatibility complex class I polypeptide-related sequences A and B (MICA and MICB, respectively) and B7H6 in patient sera were measured using enzyme-linked immunosorbent assay kits. Data were statistically compared between those with metabolic-associated steatotic liver (MASL, n = 25) and those with metabolic dysfunction-associated steatohepatitis (MASH, n = 44). The clinical characteristics related to higher concentrations of each NK cell-activating receptor ligand were also investigated.

resultsThe MASH group had a higher level of the ligands than the MASL group. Furthermore, the MASH group had a significantly higher level of the Mac-2-binding protein glycosylation isomer (M2BPGi) than the MASL group (p < 0.001). MICA and MICB were positively correlated, and all three ligands were strongly correlated with alpha-fetoprotein and protein induced by vitamin K absence 2. Although MICB levels positively correlated with aspartate transaminase and alanine transaminase levels (p < 0.005), patients with higher MICA and B7H6 levels had higher M2BPGi levels. Interestingly, concentrations of B7H6 were significantly correlated with portal inflammation (p < 0.001), rather than lobular inflammation.

conclusionThe three NK-activating receptor ligands were higher in the sera of the MASH group than those of the MASL group and strongly correlated with tumor markers, indicating the potential for hepatocarcinogenesis. Higher concentrations of serum B7H6 were correlated with advanced fibrosis and the degree of portal inflammation, which is a potential biomarker for predicting the pathogenesis of MASH.

Indexed as

B7 AntigensFatty LiverHistocompatibility Antigens Class IAdultAgedBiomarkersFemaleHumansKiller Cells, NaturalLigandsLiver NeoplasmsMaleMiddle AgedB7 AntigensBiomarkersHistocompatibility Antigens Class ILigandsMHC class I-related chain AMICB antigenB7H6, MICAMASHMASLDMICBNK cell

Identifiers

PMID40085416

What OpenQuestion holds

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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.