The Risk of Developing Hepatocellular Carcinoma Persists in Chronic Hepatitis B Patients Even After the Long-Term Administration of Nucleos(t)ide Analogs

Murai, Kazuhiro; Hikita, Hayato; Yamada, Ryoko; Nishimura, Yuki; Miyazaki, Masanori; Ishida, Hisashi; Hosui, Atsushi; Sakamori, Ryotaro; Tatsumi, Nobuyuki; Ohkawa, Kazuyoshi; Doi, Yoshinori; Nawa, Takatoshi; Egawa, Satoshi; Yoshida, Yuichi; Nozaki, Yasutoshi; Imanaka, Kazuho; Nakahara, Masanori; Sakakibara, Mitsuru; Yakushijin, Takayuki; Ogawa, Hiroyuki; Usui, Takeo; Matsumoto, Kengo; Oze, Tsugiko; Kuriki, Shinji; Sometani, Emi; Sung, Jihyun; Shimoda, Akiyoshi; Shigeno, Satoshi; Maesaka, Kazuki; Shirai, Kumiko; Doi, Akira; Tahata, Yuki; Saito, Yoshinobu; Kodama, Takahiro; Tatsumi, Tomohide; Yamada, Tomomi; Takehara, Tetsuo

doi:https://doi.org/10.1111/hepr.14225

The Risk of Developing Hepatocellular Carcinoma Persists in Chronic Hepatitis B Patients Even After the Long-Term Administration of Nucleos(t)ide Analogs

Murai, Kazuhiro; Hikita, Hayato; Yamada, Ryoko et al.

Hepatology Research, 2025, 55(9), 1228-1238

Number of Access:94（2025-10-17 13:37 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102751

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Title	The Risk of Developing Hepatocellular Carcinoma Persists in Chronic Hepatitis B Patients Even After the Long-Term Administration of Nucleos(t)ide Analogs
Creator	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
	NRID 1000020623044 1000020623044 researchmap permalink hikitahayato hikitahayato Scopus Author ID 23667454900 23667454900 ORCID 0000-0003-2488-7315 0000-0003-2488-7315 CreatorName Hikita, Hayato
	CreatorName Yamada, Ryoko
	CreatorName Nishimura, Yuki
	CreatorName Miyazaki, Masanori
	CreatorName Ishida, Hisashi
	NRID 1000010536882 1000010536882 CreatorName Hosui, Atsushi
	NRID 1000010644685 1000010644685 CreatorName Sakamori, Ryotaro
	CreatorName Tatsumi, Nobuyuki
	NRID 1000080432540 1000080432540 CreatorName Ohkawa, Kazuyoshi
	CreatorName Doi, Yoshinori
	CreatorName Nawa, Takatoshi
	CreatorName Egawa, Satoshi
	CreatorName Yoshida, Yuichi
	CreatorName Nozaki, Yasutoshi
	CreatorName Imanaka, Kazuho
	CreatorName Nakahara, Masanori
	CreatorName Sakakibara, Mitsuru
	CreatorName Yakushijin, Takayuki
	CreatorName Ogawa, Hiroyuki
	CreatorName Usui, Takeo
	CreatorName Matsumoto, Kengo
	NRID 1000030623582 1000030623582 CreatorName Oze, Tsugiko
	CreatorName Kuriki, Shinji
	CreatorName Sometani, Emi
	CreatorName Sung, Jihyun
	CreatorName Shimoda, Akiyoshi
	NRID 1000090997321 1000090997321 researchmap permalink satoshi_shigeno satoshi_shigeno Scopus Author ID 57438756400 57438756400 CreatorName Shigeno, Satoshi
	NRID 1000080974857 1000080974857 ORCID 0009-0007-5642-9470 0009-0007-5642-9470 researchmap permalink maesaka maesaka Scopus Author ID 57205239322 57205239322 CreatorName Maesaka, Kazuki
	NRID 1000020992267 1000020992267 researchmap permalink u987841f u987841f CreatorName Shirai, Kumiko
	CreatorName Doi, Akira
	NRID 1000000838047 1000000838047 ORCID 0000-0002-9116-7054 0000-0002-9116-7054 researchmap permalink yuki.tahata yuki.tahata Scopus Author ID 56755390400 56755390400 CreatorName Tahata, Yuki
	NRID 1000060814598 1000060814598 ORCID 0000-0002-0624-0449 0000-0002-0624-0449 researchmap permalink saito_yoshinobu saito_yoshinobu Scopus Author ID 55912459300 55912459300 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
	NRID 1000020397699 1000020397699 researchmap permalink read0140669 read0140669 Scopus Author ID 7202112131 7202112131 CreatorName Tatsumi, Tomohide
	NRID 1000060363371 1000060363371 researchmap permalink ymd ymd Scopus Author ID 35254679600 35254679600 CreatorName Yamada, Tomomi
	NRID 1000070335355 1000070335355 CreatorName Takehara, Tetsuo
Subject	CHB
	cirrhosis
	HBV
	HCC
	NUC
Description	Murai K., Hikita H., Yamada R., et al. The Risk of Developing Hepatocellular Carcinoma Persists in Chronic Hepatitis B Patients Even After the Long-Term Administration of Nucleos(t)ide Analogs. Hepatology Research 55, 1228 (2025); https://doi.org/10.1111/hepr.14225.
Abstract	Background and Aim: Nucleos(t)ide analogs (NUCs) are used in the treatment of chronic hepatitis B (CHB). It is still uncertain whether the risk of incident hepatocellular carcinoma (HCC) continues beyond 5 or 10 years after the initiation of NUC treatment. We aimed to elucidate this in CHB patients receiving long-term NUC treatment. Methods: This was a multicenter, observational study that included patients who began NUC treatment between July 2000 and March 2019; patients were retrospectively enrolled up to March 2019 and followed up until August 2024. Results: Among 737 CHB patients (156 with cirrhosis) who started NUC treatment, 147 developed HCC during a median follow-up period of 144.2 months. The 5-, 10-, and 15-year cumulative HCC rates were 11.2%, 18.4%, and 23.1%, respectively. Independent risk factors for subsequent HCC occurrence included older age, male sex, cirrhosis, low platelet count, low ALT levels, and high γ-GTP levels at NUC initiation. After 5 years, the risk factors were cirrhosis, high γ-GTP levels, and high AFP levels, whereas after 10 years, they were cirrhosis and diabetes. Landmark analysis revealed that the 5-year cumulative HCC incidence was 8.1% at 5 years and 5.8% at 10 years after NUC initiation. In noncirrhotic patients, cumulative HCC incidence at 5 years was 5.8%, whereas 5-year cumulative incidences starting at 5 and 10 years were 4.1% and 4.8%, respectively, remaining stable over time. Conclusion: The risk of HCC persists long after NUC initiation. In noncirrhotic patients, the risk remains stable more than 10 years after NUC treatment initiation.
Publisher	John Wiley and Sons Inc
Source Title	Hepatology Research
Volume (Issue)	55(9)
Page	1228-1238
Date of Issued	2025-06-16
Language	English
Handle URL	https://hdl.handle.net/11094/102751
PISSN	13866346
eISSN	1872034X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1111/hepr.14225
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
DCMI Type	Text
DCTERMS.bibliographicCitation	Hepatology Research. 2025, 55(9), p. 1228-1238
DC.title	The Risk of Developing Hepatocellular Carcinoma Persists in Chronic Hepatitis B Patients Even After the Long-Term Administration of Nucleos(t)ide Analogs
DC.creator	Murai, Kazuhiro
	Hikita, Hayato
	Yamada, Ryoko
	Nishimura, Yuki
	Miyazaki, Masanori
	Ishida, Hisashi
	Hosui, Atsushi
	Sakamori, Ryotaro
	Tatsumi, Nobuyuki
	Ohkawa, Kazuyoshi
	Doi, Yoshinori
	Nawa, Takatoshi
	Egawa, Satoshi
	Yoshida, Yuichi
	Nozaki, Yasutoshi
	Imanaka, Kazuho
	Nakahara, Masanori
	Sakakibara, Mitsuru
	Yakushijin, Takayuki
	Ogawa, Hiroyuki
	Usui, Takeo
	Matsumoto, Kengo
	Oze, Tsugiko
	Kuriki, Shinji
	Sometani, Emi
	Sung, Jihyun
	Shimoda, Akiyoshi
	Shigeno, Satoshi
	Maesaka, Kazuki
	Shirai, Kumiko
	Doi, Akira
	Tahata, Yuki
	Saito, Yoshinobu
	Kodama, Takahiro
	Tatsumi, Tomohide
	Yamada, Tomomi
	Takehara, Tetsuo
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-06-16
DC.identifier	https://doi.org/10.1111/hepr.14225
DC.subject	CHB
	cirrhosis
	HBV
	HCC
	NUC
DC.description	Murai K., Hikita H., Yamada R., et al. The Risk of Developing Hepatocellular Carcinoma Persists in Chronic Hepatitis B Patients Even After the Long-Term Administration of Nucleos(t)ide Analogs. Hepatology Research 55, 1228 (2025); https://doi.org/10.1111/hepr.14225.
DCTERMS.abstract	Background and Aim: Nucleos(t)ide analogs (NUCs) are used in the treatment of chronic hepatitis B (CHB). It is still uncertain whether the risk of incident hepatocellular carcinoma (HCC) continues beyond 5 or 10 years after the initiation of NUC treatment. We aimed to elucidate this in CHB patients receiving long-term NUC treatment. Methods: This was a multicenter, observational study that included patients who began NUC treatment between July 2000 and March 2019; patients were retrospectively enrolled up to March 2019 and followed up until August 2024. Results: Among 737 CHB patients (156 with cirrhosis) who started NUC treatment, 147 developed HCC during a median follow-up period of 144.2 months. The 5-, 10-, and 15-year cumulative HCC rates were 11.2%, 18.4%, and 23.1%, respectively. Independent risk factors for subsequent HCC occurrence included older age, male sex, cirrhosis, low platelet count, low ALT levels, and high γ-GTP levels at NUC initiation. After 5 years, the risk factors were cirrhosis, high γ-GTP levels, and high AFP levels, whereas after 10 years, they were cirrhosis and diabetes. Landmark analysis revealed that the 5-year cumulative HCC incidence was 8.1% at 5 years and 5.8% at 10 years after NUC initiation. In noncirrhotic patients, cumulative HCC incidence at 5 years was 5.8%, whereas 5-year cumulative incidences starting at 5 and 10 years were 4.1% and 4.8%, respectively, remaining stable over time. Conclusion: The risk of HCC persists long after NUC initiation. In noncirrhotic patients, the risk remains stable more than 10 years after NUC treatment initiation.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	102751
citation_title	The Risk of Developing Hepatocellular Carcinoma Persists in Chronic Hepatitis B Patients Even After the Long-Term Administration of Nucleos(t)ide Analogs
citation_author	Murai, Kazuhiro
	Hikita, Hayato
	Yamada, Ryoko
	Nishimura, Yuki
	Miyazaki, Masanori
	Ishida, Hisashi
	Hosui, Atsushi
	Sakamori, Ryotaro
	Tatsumi, Nobuyuki
	Ohkawa, Kazuyoshi
	Doi, Yoshinori
	Nawa, Takatoshi
	Egawa, Satoshi
	Yoshida, Yuichi
	Nozaki, Yasutoshi
	Imanaka, Kazuho
	Nakahara, Masanori
	Sakakibara, Mitsuru
	Yakushijin, Takayuki
	Ogawa, Hiroyuki
	Usui, Takeo
	Matsumoto, Kengo
	Oze, Tsugiko
	Kuriki, Shinji
	Sometani, Emi
	Sung, Jihyun
	Shimoda, Akiyoshi
	Shigeno, Satoshi
	Maesaka, Kazuki
	Shirai, Kumiko
	Doi, Akira
	Tahata, Yuki
	Saito, Yoshinobu
	Kodama, Takahiro
	Tatsumi, Tomohide
	Yamada, Tomomi
	Takehara, Tetsuo
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2025-06-16
citation_journal_title	Hepatology Research
citation_volume	55
citation_issue	9
citation_firstpage	1228
citation_lastpage	1238
citation_doi	https://doi.org/10.1111/hepr.14225
citation_public_url	https://hdl.handle.net/11094/102751

The Risk of Developing Hepatocellular Carcinoma Persists in Chronic Hepatitis B Patients Even After the Long-Term Administration of Nucleos(t)ide Analogs

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