Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis

Kumazaki, Shusuke; Hikita, Hayato; Tahata, Yuki; Sung, Ji Hyun; Fukumoto, Kenji; Myojin, Yuta; Sakane, Sadatsugu; Murai, Kazuhiro; Sasaki, Yoichi; Shirai, Kumiko; Saito, Yoshinobu; Kodama, Takahiro; Kakita, Naruyasu; Takahashi, Hirokazu; Toyoda, Hidenori; Suda, Goki; Morii, Eiichi; Kojima, Takashi; Ebihara, Takeshi; Shimizu, Kentaro; Sasaki, Yutaka; Tatsumi, Tomohide; Takehara, Tetsuo

doi:https://doi.org/10.1111/apt.18063

Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis

Kumazaki, Shusuke; Hikita, Hayato; Tahata, Yuki et al.

Alimentary Pharmacology and Therapeutics, 2024, 60(3), 327-339

Number of Access:3,399（2025-07-18 12:21 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/97149

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Title	Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis
Creator	CreatorName Kumazaki, Shusuke
	NRID 1000020623044 1000020623044 researchmap permalink hikitahayato hikitahayato Scopus Author ID 23667454900 23667454900 CreatorName Hikita, Hayato
	NRID 1000000838047 1000000838047 researchmap permalink yuki.tahata yuki.tahata Scopus Author ID 56755390400 56755390400 CreatorName Tahata, Yuki
	CreatorName Sung, Ji Hyun
	CreatorName Fukumoto, Kenji
	CreatorName Myojin, Yuta
	NRID 1000030817515 1000030817515 CreatorName Sakane, Sadatsugu
	NRID 1000050867314 1000050867314 ORCID 0000-0001-8634-2922 0000-0001-8634-2922 researchmap permalink murai_kazuhiro murai_kazuhiro Scopus Author ID 57202460806 57202460806 CreatorName Murai, Kazuhiro
	CreatorName Sasaki, Yoichi
	NRID 1000020992267 1000020992267 researchmap permalink u987841f u987841f CreatorName Shirai, Kumiko
	ORCID 0000-0002-0624-0449 0000-0002-0624-0449 researchmap permalink saito_yoshinobu saito_yoshinobu Scopus Author ID 55912459300 55912459300 NRID 1000060814598 1000060814598 CreatorName Saito, Yoshinobu
	NRID 1000010623275 1000010623275 ORCID 0000-0002-6250-1324 0000-0002-6250-1324 researchmap permalink takahirokodama takahirokodama Scopus Author ID 35193885800 35193885800 CreatorName Kodama, Takahiro
	CreatorName Kakita, Naruyasu
	NRID 1000020607783 1000020607783 CreatorName Takahashi, Hirokazu
	CreatorName Toyoda, Hidenori
	NRID 1000020447460 1000020447460 CreatorName Suda, Goki
	NRID 1000010283772 1000010283772 ORCID 0000-0001-8490-3650 0000-0001-8490-3650 researchmap permalink read0046454 read0046454 Scopus Author ID 7003914326 7003914326 CreatorName Morii, Eiichi
	CreatorName Kojima, Takashi
	NRID 1000010813975 1000010813975 ORCID 0000-0003-4101-0419 0000-0003-4101-0419 researchmap permalink ebihara830 ebihara830 CreatorName Ebihara, Takeshi
	NRID 1000060379203 1000060379203 researchmap permalink kentaroshimizu kentaroshimizu Scopus Author ID 55303276200 55303276200 CreatorName Shimizu, Kentaro
	CreatorName Sasaki, Yutaka
	NRID 1000020397699 1000020397699 researchmap permalink read0140669 read0140669 Scopus Author ID 7202112131 7202112131 CreatorName Tatsumi, Tomohide
	NRID 1000070335355 1000070335355 researchmap permalink takeharatetsuo takeharatetsuo Scopus Author ID 7103332258 7103332258 CreatorName Takehara, Tetsuo
Description	Kumazaki S., Hikita H., Tahata Y., et al. Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis. Alimentary Pharmacology and Therapeutics , (2024); https://doi.org/10.1111/apt.18063.
Abstract	Background and Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) patients with a Fib-4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high-risk populations requiring follow-up is needed. We explored the utility of serum levels of growth differentiation factor-15 (GDF15), a cell stress-responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. Methods: Serum GDF15 levels were measured in 518 biopsy-performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. Results: In the biopsy-MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib-4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high-GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib-4 index <1.3 or low-GDF15 rarely developed liver cancer, high-GDF15 patients with a Fib-4 index >1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high-GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low-GDF15 patients, whether limited to high-Fib-4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib-4 index >1.3, 2.7% had a Fib-4 index >1.3 and >1.75 ng/mL GDF15. Conclusions: Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance.
Publisher	John Wiley and Sons Inc
Source Title	Alimentary Pharmacology and Therapeutics
Volume (Issue)	60(3)
Page	327-339
Date of Issued	2024-06-03
Language	English
Handle URL	https://hdl.handle.net/11094/97149
PISSN	02692813
eISSN	13652036
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1111/apt.18063
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Alimentary Pharmacology and Therapeutics. 2024, 60(3), p. 327-339
DC.title	Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis
DC.creator	Kumazaki, Shusuke
	Hikita, Hayato
	Tahata, Yuki
	Sung, Ji Hyun
	Fukumoto, Kenji
	Myojin, Yuta
	Sakane, Sadatsugu
	Murai, Kazuhiro
	Sasaki, Yoichi
	Shirai, Kumiko
	Saito, Yoshinobu
	Kodama, Takahiro
	Kakita, Naruyasu
	Takahashi, Hirokazu
	Toyoda, Hidenori
	Suda, Goki
	Morii, Eiichi
	Kojima, Takashi
	Ebihara, Takeshi
	Shimizu, Kentaro
	Sasaki, Yutaka
	Tatsumi, Tomohide
	Takehara, Tetsuo
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-06-03
DC.identifier	https://doi.org/10.1111/apt.18063
DC.description	Kumazaki S., Hikita H., Tahata Y., et al. Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis. Alimentary Pharmacology and Therapeutics , (2024); https://doi.org/10.1111/apt.18063.
DCTERMS.abstract	Background and Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) patients with a Fib-4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high-risk populations requiring follow-up is needed. We explored the utility of serum levels of growth differentiation factor-15 (GDF15), a cell stress-responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. Methods: Serum GDF15 levels were measured in 518 biopsy-performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. Results: In the biopsy-MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib-4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high-GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib-4 index <1.3 or low-GDF15 rarely developed liver cancer, high-GDF15 patients with a Fib-4 index >1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high-GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low-GDF15 patients, whether limited to high-Fib-4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib-4 index >1.3, 2.7% had a Fib-4 index >1.3 and >1.75 ng/mL GDF15. Conclusions: Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	97149
citation_title	Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis
citation_author	Kumazaki, Shusuke
	Hikita, Hayato
	Tahata, Yuki
	Sung, Ji Hyun
	Fukumoto, Kenji
	Myojin, Yuta
	Sakane, Sadatsugu
	Murai, Kazuhiro
	Sasaki, Yoichi
	Shirai, Kumiko
	Saito, Yoshinobu
	Kodama, Takahiro
	Kakita, Naruyasu
	Takahashi, Hirokazu
	Toyoda, Hidenori
	Suda, Goki
	Morii, Eiichi
	Kojima, Takashi
	Ebihara, Takeshi
	Shimizu, Kentaro
	Sasaki, Yutaka
	Tatsumi, Tomohide
	Takehara, Tetsuo
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2024-06-03
citation_journal_title	Alimentary Pharmacology and Therapeutics
citation_volume	60
citation_issue	3
citation_firstpage	327
citation_lastpage	339
citation_doi	https://doi.org/10.1111/apt.18063
citation_public_url	https://hdl.handle.net/11094/97149

Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis

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