High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs

Sometani, Emi; Hikita, Hayato; Murai, Kazuhiro; Toyoda, Hidenori; Tanaka, Satoshi; Oze, Tsugiko; Sung, Jihyun; Shimoda, Akiyoshi; Fukuoka, Makoto; Shigeno, Satoshi; Fukutomi, Keisuke; Shirai, Kumiko; Tahata, Yuki; Saito, Yoshinobu; Nishio, Akira; Furuta, Kunimaro; Kodama, Takahiro; Sakamori, Ryotaro; Tatsumi, Tomohide; Mita, Eiji; Umezawa, Akihiro; Tanaka, Yasuhito; Takehara, Tetsuo

doi:https://doi.org/10.1111/hepr.14111

High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs

Sometani, Emi; Hikita, Hayato; Murai, Kazuhiro et al.

Hepatology Research, 2024, 55(1), 22-33

Number of Access:2,972（2025-07-18 13:12 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98305

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Title	High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs
Creator	CreatorName Sometani, Emi
	NRID 1000020623044 1000020623044 researchmap permalink hikitahayato hikitahayato Scopus Author ID 23667454900 23667454900 CreatorName Hikita, Hayato
	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 Toyoda, Hidenori
	CreatorName Tanaka, Satoshi
	CreatorName Oze, Tsugiko
	CreatorName Sung, Jihyun
	CreatorName Shimoda, Akiyoshi
	CreatorName Fukuoka, Makoto
	CreatorName Shigeno, Satoshi
	CreatorName Fukutomi, Keisuke
	NRID 1000020992267 1000020992267 researchmap permalink u987841f u987841f CreatorName Shirai, Kumiko
	NRID 1000000838047 1000000838047 researchmap permalink yuki.tahata yuki.tahata Scopus Author ID 56755390400 56755390400 CreatorName Tahata, Yuki
	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 1000050934907 1000050934907 ORCID 0000-0003-1668-0779 0000-0003-1668-0779 researchmap permalink akira.nishio akira.nishio Scopus Author ID 57192072189 57192072189 CreatorName Nishio, Akira
	NRID 1000050773834 1000050773834 researchmap permalink knmrfrt knmrfrt CreatorName Furuta, Kunimaro
	NRID 1000010623275 1000010623275 ORCID 0000-0002-6250-1324 0000-0002-6250-1324 researchmap permalink takahirokodama takahirokodama Scopus Author ID 35193885800 35193885800 CreatorName Kodama, Takahiro
	NRID 1000010644685 1000010644685 ORCID 0000-0002-1580-607X 0000-0002-1580-607X researchmap permalink sakamori sakamori CreatorName Sakamori, Ryotaro
	NRID 1000020397699 1000020397699 researchmap permalink read0140669 read0140669 Scopus Author ID 7202112131 7202112131 CreatorName Tatsumi, Tomohide
	CreatorName Mita, Eiji
	NRID 1000070213486 1000070213486 CreatorName Umezawa, Akihiro
	NRID 1000090336694 1000090336694 CreatorName Tanaka, Yasuhito
	NRID 1000070335355 1000070335355 researchmap permalink takeharatetsuo takeharatetsuo Scopus Author ID 7103332258 7103332258 CreatorName Takehara, Tetsuo
Subject	cccDNA
	CHB
	NUC
Description	Sometani E., Hikita H., Murai K., et al. High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs. Hepatology Research, (2024); https://doi.org/10.1111/hepr.14111.
Abstract	Aim: Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core-related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C. Methods: We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.0 log IU/mL. We measured the serum levels of HBV RNA and GDF15. Results: Among 242 CHB patients, 57 had detectable HBV RNA, and GDF15 was quantified in all patients. The median GDF15 level was 0.86 ng/mL. Cox proportional hazards analysis revealed that male sex and higher GDF15, FIB-4 index, alpha-fetoprotein and gamma-glutamyl transpeptidase were independent risk factors for HCC. The presence of HBV RNA above the lower limit of quantification was not a risk factor. When we set cutoff values based on the Youden index, the cumulative incidence of HCC was significantly higher in the male, AFP ≥3.0 ng/mL, gamma-glutamyl transpeptidase ≥22 U/L, FIB-4 index ≥1.93, and GDF-15 ≥1.17 ng/mL groups. In patients with no or more than three of these five risk factors, the 10-year HCC cumulative incidence rates were 0% and 41.0%, respectively. Conclusions: High serum GDF15 is an independent risk factor for the occurrence of HCC in CHB patients treated with nucleos(t)ide analogs.
Publisher	John Wiley and Sons Inc
Source Title	Hepatology Research
Volume (Issue)	55(1)
Page	22-33
Date of Issued	2024-09-18
Language	English
Handle URL	https://hdl.handle.net/11094/98305
PISSN	13866346
eISSN	1872034X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1111/hepr.14111
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	Hepatology Research. 2024, 55(1), p. 22-33
DC.title	High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs
DC.creator	Sometani, Emi
	Hikita, Hayato
	Murai, Kazuhiro
	Toyoda, Hidenori
	Tanaka, Satoshi
	Oze, Tsugiko
	Sung, Jihyun
	Shimoda, Akiyoshi
	Fukuoka, Makoto
	Shigeno, Satoshi
	Fukutomi, Keisuke
	Shirai, Kumiko
	Tahata, Yuki
	Saito, Yoshinobu
	Nishio, Akira
	Furuta, Kunimaro
	Kodama, Takahiro
	Sakamori, Ryotaro
	Tatsumi, Tomohide
	Mita, Eiji
	Umezawa, Akihiro
	Tanaka, Yasuhito
	Takehara, Tetsuo
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-09-18
DC.identifier	https://doi.org/10.1111/hepr.14111
DC.subject	cccDNA
	CHB
	NUC
DC.description	Sometani E., Hikita H., Murai K., et al. High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs. Hepatology Research, (2024); https://doi.org/10.1111/hepr.14111.
DCTERMS.abstract	Aim: Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core-related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C. Methods: We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.0 log IU/mL. We measured the serum levels of HBV RNA and GDF15. Results: Among 242 CHB patients, 57 had detectable HBV RNA, and GDF15 was quantified in all patients. The median GDF15 level was 0.86 ng/mL. Cox proportional hazards analysis revealed that male sex and higher GDF15, FIB-4 index, alpha-fetoprotein and gamma-glutamyl transpeptidase were independent risk factors for HCC. The presence of HBV RNA above the lower limit of quantification was not a risk factor. When we set cutoff values based on the Youden index, the cumulative incidence of HCC was significantly higher in the male, AFP ≥3.0 ng/mL, gamma-glutamyl transpeptidase ≥22 U/L, FIB-4 index ≥1.93, and GDF-15 ≥1.17 ng/mL groups. In patients with no or more than three of these five risk factors, the 10-year HCC cumulative incidence rates were 0% and 41.0%, respectively. Conclusions: High serum GDF15 is an independent risk factor for the occurrence of HCC in CHB patients treated with nucleos(t)ide analogs.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	98305
citation_title	High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs
citation_author	Sometani, Emi
	Hikita, Hayato
	Murai, Kazuhiro
	Toyoda, Hidenori
	Tanaka, Satoshi
	Oze, Tsugiko
	Sung, Jihyun
	Shimoda, Akiyoshi
	Fukuoka, Makoto
	Shigeno, Satoshi
	Fukutomi, Keisuke
	Shirai, Kumiko
	Tahata, Yuki
	Saito, Yoshinobu
	Nishio, Akira
	Furuta, Kunimaro
	Kodama, Takahiro
	Sakamori, Ryotaro
	Tatsumi, Tomohide
	Mita, Eiji
	Umezawa, Akihiro
	Tanaka, Yasuhito
	Takehara, Tetsuo
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2024-09-18
citation_journal_title	Hepatology Research
citation_volume	55
citation_issue	1
citation_firstpage	22
citation_lastpage	33
citation_doi	https://doi.org/10.1111/hepr.14111
citation_public_url	https://hdl.handle.net/11094/98305

High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs

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