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

アクセス数:2,732件（2025-07-06 17:40 集計）

固定URL: https://hdl.handle.net/11094/98305

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タイトル	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
著者	著者名 Sometani, Emi
	NRID 1000020623044 1000020623044 researchmap permalink hikitahayato hikitahayato Scopus Author ID 23667454900 23667454900 著者名 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 著者名 Murai, Kazuhiro
	著者名 Toyoda, Hidenori
	著者名 Tanaka, Satoshi
	著者名 Oze, Tsugiko
	著者名 Sung, Jihyun
	著者名 Shimoda, Akiyoshi
	著者名 Fukuoka, Makoto
	著者名 Shigeno, Satoshi
	著者名 Fukutomi, Keisuke
	NRID 1000020992267 1000020992267 researchmap permalink u987841f u987841f 著者名 Shirai, Kumiko
	NRID 1000000838047 1000000838047 researchmap permalink yuki.tahata yuki.tahata Scopus Author ID 56755390400 56755390400 著者名 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 著者名 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 著者名 Nishio, Akira
	NRID 1000050773834 1000050773834 researchmap permalink knmrfrt knmrfrt 著者名 Furuta, Kunimaro
	NRID 1000010623275 1000010623275 ORCID 0000-0002-6250-1324 0000-0002-6250-1324 researchmap permalink takahirokodama takahirokodama Scopus Author ID 35193885800 35193885800 著者名 Kodama, Takahiro
	NRID 1000010644685 1000010644685 ORCID 0000-0002-1580-607X 0000-0002-1580-607X researchmap permalink sakamori sakamori 著者名 Sakamori, Ryotaro
	NRID 1000020397699 1000020397699 researchmap permalink read0140669 read0140669 Scopus Author ID 7202112131 7202112131 著者名 Tatsumi, Tomohide
	著者名 Mita, Eiji
	NRID 1000070213486 1000070213486 著者名 Umezawa, Akihiro
	NRID 1000090336694 1000090336694 著者名 Tanaka, Yasuhito
	NRID 1000070335355 1000070335355 researchmap permalink takeharatetsuo takeharatetsuo Scopus Author ID 7103332258 7103332258 著者名 Takehara, Tetsuo
キーワード等	cccDNA
	CHB
	NUC
内容	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.
抄録	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.
出版者	John Wiley and Sons Inc
収録物名	Hepatology Research
巻(号)	55(1)
ページ	22-33
刊行年月	2024-09-18
言語	英語
ハンドルURL	https://hdl.handle.net/11094/98305
PISSN	13866346
eISSN	1872034X
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1111/hepr.14111
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
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	英語
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	英語
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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