Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update

Abstract

The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other's work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.

Keywords: Consensus statement; Diagnosis; Hepatocellular carcinoma; Japan Society of Hepatology; Pathology; Treatment.

Conflict of interest statement

M.K. received honoraria from Eisai, Bayer, MSD, Bristol-Myers Squibb, Lilly, and EA Pharma and grants from Gilead Sciences, Taiho, Sumitomo Dainippon Pharma, Takeda, Otsuka, EA Pharma, Abbvie, and Eisai and has had an advisory role in Eisai, Ono, MSD, Bristol-Myers Squibb, and Roche. Y.K. received honoraria from Esiai. K.H. received honoraria from Taiho, Chugai, and Takeda. R.T. received honoraria from Abbvie, Bayer, Chugai, Eisai, Fujifilm Wako, GE Healthcare, Gilead Sciences, Medtronic, MSD, Otsuka, Shionogi, and Sumitomo Dainippon. K.K. has no conflicts of interest to declare. S.S. has no conflicts of interest to declare. H.T. received honoraria from AbbVie, MSD, and Bayer. Y.I. has no conflicts of interest to declare. A.H. received honoraria from Eisai, Bayer, and Otsuka. M.I. received honoraria from Eisai, Bayer, and Lilly and research funding from Bayer, Eisai, Ono, Bristol Myers Squibb, AstraZeneca, Chugai, Merck Serono, Novartis Pharma, and MSD. N.I. received honoraria from Bayer and Eisai. M.M. received honoraria from Eisai, Bayer, and Lilly. S.O. received honoraria from Bayer, Eisai, and Eli Lilly; consulting or advisory fees from Bayer, Eisai, Merck & Co., Inc., Chugai Pharma, Eli Lilly, and AstraZeneca; and research grants from Bayer, Eisai, and Eli Lilly. Y.M. has no conflicts of interest to declare. K.U. received honoraria from Eisai and Eli Lilly. T.M. has no conflicts of interest to declare. S.M. received honoraria from Eisai, Bayer, Guerbet, Asahi Intecc, Philips, Canon, Piolax, Daiichi-Sankyo, Fujiyakuhin, and Eli Lilly. O.N. has no conflicts of interest to declare. H.Y. has no conflicts of interest to declare. M.S. received grants from Eisai, Olympus, Fujifilm, and CYTLIMIC. E.H. has no conflicts of interest to declare. M.S. received grants from EA Pharma, Eisai, Covidien Japan, Novartis Pharma, Taiho, Chugai, Bayer, Astellas, Ono, and Takeda. N.K. has no conflicts of interest to declare. S.M. has no conflicts of interest to declare. T.T. received honoraria from Gilead Sciences, AbbVie, and MAD and grant/research support from Gilead Sciences, AbbVie, MSD, Janssen, Eisai, EA Pharma, and Otsuka.

Copyright © 2021 by S. Karger AG, Basel.

Figures

Fig. 1

Schematic representation of gross pathological type of HCC. HCC, hepatocellular carcinoma. Reproduced with permission from the Liver Cancer Study Group of Japan [20].

Fig. 2

Surveillance and diagnostic algorithm of HCC. HCC, hepatocellular carcinoma; CT, computed tomography; MRI, magnetic resonance imaging; CTAP, CT during arterioportography; CTAH, CT during hepatic arteriography; US, ultrasound. Reproduced with permission from the Japan Society of Hepatology [8], Kokudo et al. [9], and the Japan Society of Hepatology [17].

Fig. 3

Treatment strategy after TACE failure/refractoriness. TACE, transarterial chemoembolization; MTA, molecular targeted agents; HAIC, hepatic arterial infusion chemotherapy. * BSC, best supportive care. + HAIC or ablation may be a choice of treatment. Reproduced with permission from the Japan Society of Hepatology [17].

Fig. 4

Effect of anti-VEGF on tumor vessels. VEGF, vascular endothelial growth factor; TACE, transarterial chemoembolization. Modified with permission from the Japan Society of Hepatology [17].

Fig. 5

Complementary role of TACE and lenvatinib. TACE, transarterial chemoembolization; VEGF, vascular endothelial growth factor. Reproduced with permission from the Japan Society of Hepatology [17].

Fig. 6

Changing paradigm of treatment strategy in TACE-unsuitable intermediate-stage HCC. HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization. Reproduced with permission from the Japan Society of Hepatology [17].

Fig. 7

New paradigm of treatment strategy for unresectable HCC. HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; BCLC, Barcelona Clinic Liver Cancer. Reproduced with permission from the Japan Society of Hepatology [17].

Fig. 8

Treatment strategy for bilobar multifocal intermediate-stage HCC (TACE-unsuitable HCC). HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization. Reproduced with permission from the Japan Society of Hepatology [17].

Fig. 10

Ongoing phase 3 trials in HCC. HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; PBO, placebo; LEN, lenvatinib; SOR, sorafenib. Reproduced with permission from the Japan Society of Hepatology [17].

Fig. 9

Possible sequential systemic therapy for HCC. HCC, hepatocellular carcinoma. Reproduced with permission from the Japan Society of Hepatology [17].

Fig. 11

Treatment algorithm. HCC, hepatocellular carcinoma; HAIC, hepatic arterial infusion chemotherapy; RFA, radiofrequency ablation; TACE, transarterial chemoembolization; RFA, radiofrequency ablation; Systemic Tx, molecular targeted therapy and/or combination immunotherapy. Reproduced with permission from the Japan Society of Hepatology [8], Kokudo et al. [9], and the Japan Society of Hepatology [17].