Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2021 Aug 17;11(1):16663.
doi: 10.1038/s41598-021-96089-x.

Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study

Atsushi Hiraoka  1 , Takashi Kumada  2 , Toshifumi Tada  3 , Joji Tani  4 , Kazuya Kariyama  5 , Shinya Fukunishi  6 , Masanori Atsukawa  7 , Masashi Hirooka  8 , Kunihiko Tsuji  9 , Toru Ishikawa  10 , Koichi Takaguchi  11 , Ei Itobayashi  12 , Kazuto Tajiri  13 , Noritomo Shimada  14 , Hiroshi Shibata  15 , Hironori Ochi  16 , Kazuhito Kawata  17 , Satoshi Yasuda  18 , Hidenori Toyoda  18 , Tomoko Aoki  19 , Takaaki Tanaka  20 , Hideko Ohama  6 , Kazuhiro Nouso  5 , Akemi Tsutsui  11 , Takuya Nagano  11 , Norio Itokawa  7 , Taeang Arai  7 , Tomomi Okubo  7 , Michitaka Imai  10 , Yohei Koizumi  8 , Shinichiro Nakamura  3 , Koji Joko  16 , Yoichi Hiasa  8 , Masatoshi Kudo  19 ; Real-life Practice Experts for HCC (RELPEC) Study Group and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)
Affiliations
Multicenter Study

Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study

Atsushi Hiraoka et al. Sci Rep. .

Abstract

It was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child-Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.

PubMed Disclaimer

Conflict of interest statement

Atsushi Hiraoka, MD, PhD—Lecture fees: Bayer, Eisai, Eli Lilly, Otsuka. Takashi Kumada, MD, PhD—Lecture fees: Eisai. Masatoshi Kudo, MD, PhD—Advisory role: Eiasi, Ono, MSD, Bristol-Myers Squibb, Roche; Lecture fees: Eisai, Bayer, MSD, Bristol-Myers Squibb, Eli Lilly, EA Pharma; Research funding: Gilead Sciences, Taiho, Sumitomo Dainippon Pharma, Takeda, Otsuka, EA Pharma, Abbvie, Eisai. None of the other authors have potential conflicts of interest to declare.

Figures

Figure 1
Figure 1
Flow of patient enrollment. LEN lenvatinib, AIH autoimmune hepatitis, PBC primary biliary cirrhosis.
Figure 2
Figure 2
Progression-free and overall survival for all unresectable hepatocellular carcinoma patients with Child–Pugh class A (n = 557). (a) Progression-free survival (median 7.8 months, 95% CI 7.0–8.6). b. Overall survival (median 17.8 months, 95% CI 16.3–19.5).
Figure 3
Figure 3
Progression-free and overall survival according to modified ALBI grade. (a) Progression-free survival divided by mALBI grade. mALBI 1 (median 9.8 months, 95% CI 7.8–11.6), mALBI 2a (median 8.0 months, 95% CI 6.6–9.3), mALBI 2b (6.3 months, 95% CI 4.8–7.4) (P = 0.002). (b) Overall survival divided by mALBI grade. mALBI 1 (median 21.0 months, 95% CI 17.2–26.8), mALBI 2a (median 20.0 months, 95% CI 17.8–27.9), mALBI 2b (median 11.2 months, 95% CI 9.7–14.5) (P < 0.001).
Figure 4
Figure 4
Progression-free and overall survival according to basal liver disease etiology. (a) Progression-free survival divided by basal liver disease etiology. HCV (median 7.0 months, 95% CI 5.5–8.7), HBV (median 7.9 months, 95% CI 6.8–10.5), alcohol (median 7.4 months, 95% CI 5.8–8.6), NAFLD/NASH (median 9.3 months, 95% CI 7.8–13.5), cryptogenic (median 11.9 months, 95% CI 5.2–14.4) (P = 0.154). (b) Overall survival divided by basal liver disease etiology. HCV (median 18.3 months, 95% CI 14.3–20.4), HBV (median 16.3 months, 95% CI 11.4–19.3), alcohol (median 15.3 months, 95% CI 10.5–19.2), NAFLD/NASH (median 20.5 months, 95% CI 16.8–29.5), cryptogenic (median not reached, 95% CI 18.3-not reached) (P = 0.052). (c) Progression-free survival of Viral and Non-viral (NAFLD/NASH, Cryptogenic, Alcohol) groups. Viral (median 7.5 months, 95% CI 6.4–8.5), Non-viral (median 8.3 months, 95% CI 7.4–10.0) (P = 0.092). (d) Overall survival of Viral and Non-viral (NAFLD/NASH, Cryptogenic, Alcohol) groups. Viral (median 17.2 months, 95% CI 14.4–19.3), Non-viral (median 18.5 months, 95% CI 16.3–21.7) (P = 0.226). (e) Progression-free survival of Viral/Alcohol and NAFLD/NASH/Cryptogenic groups. Viral/Alcohol (median 7.5 months, 95% CI 6.8–8.0), NAFLD/NASH/Cryptogenic (median 9.3, 95% CI 7.8–13.4) (P = 0.012). (f) Overall survival of Viral/Alcohol and NAFLD/NASH/Cryptogenic groups. Viral/Alcohol (median 16.9 months, 95% CI 14.5–18.6), NAFLD/NASH/Cryptogenic (median 21.0 months, 95% CI 17.8–33.5) (P = 0.009).
Figure 4
Figure 4
Progression-free and overall survival according to basal liver disease etiology. (a) Progression-free survival divided by basal liver disease etiology. HCV (median 7.0 months, 95% CI 5.5–8.7), HBV (median 7.9 months, 95% CI 6.8–10.5), alcohol (median 7.4 months, 95% CI 5.8–8.6), NAFLD/NASH (median 9.3 months, 95% CI 7.8–13.5), cryptogenic (median 11.9 months, 95% CI 5.2–14.4) (P = 0.154). (b) Overall survival divided by basal liver disease etiology. HCV (median 18.3 months, 95% CI 14.3–20.4), HBV (median 16.3 months, 95% CI 11.4–19.3), alcohol (median 15.3 months, 95% CI 10.5–19.2), NAFLD/NASH (median 20.5 months, 95% CI 16.8–29.5), cryptogenic (median not reached, 95% CI 18.3-not reached) (P = 0.052). (c) Progression-free survival of Viral and Non-viral (NAFLD/NASH, Cryptogenic, Alcohol) groups. Viral (median 7.5 months, 95% CI 6.4–8.5), Non-viral (median 8.3 months, 95% CI 7.4–10.0) (P = 0.092). (d) Overall survival of Viral and Non-viral (NAFLD/NASH, Cryptogenic, Alcohol) groups. Viral (median 17.2 months, 95% CI 14.4–19.3), Non-viral (median 18.5 months, 95% CI 16.3–21.7) (P = 0.226). (e) Progression-free survival of Viral/Alcohol and NAFLD/NASH/Cryptogenic groups. Viral/Alcohol (median 7.5 months, 95% CI 6.8–8.0), NAFLD/NASH/Cryptogenic (median 9.3, 95% CI 7.8–13.4) (P = 0.012). (f) Overall survival of Viral/Alcohol and NAFLD/NASH/Cryptogenic groups. Viral/Alcohol (median 16.9 months, 95% CI 14.5–18.6), NAFLD/NASH/Cryptogenic (median 21.0 months, 95% CI 17.8–33.5) (P = 0.009).
Figure 5
Figure 5
Progression-free and overall survival of NAFLD/NASH and Viral/Alcohol groups. (a) Progression-free survival. Viral/Alcohol (median 7.5 months, 95% CI 6.8–8.0), NAFLD/NASH (median 9.3 months, 95% CI 7.8–13.5) (P = 0.012). (b) Overall survival. Viral/Alcohol (median 16.9 months, 95% CI 14.5–18.6), NAFLD/NASH (median 20.5 months, 95% CI 16.8–29.5). (P = 0.057).
See this image and copyright information in PMC

References

    1. Llovet JM, et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008;359:378–390. doi: 10.1056/NEJMoa0708857. - DOI - PubMed
    1. Cheng AL, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34. doi: 10.1016/s1470-2045(08)70285-7. - DOI - PubMed
    1. Kudo M, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163–1173. doi: 10.1016/s0140-6736(18)30207-1. - DOI - PubMed
    1. Finn RS, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N. Engl. J. Med. 2020;382:1894–1905. doi: 10.1056/NEJMoa1915745. - DOI - PubMed
    1. Pfister D, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature. 2021 doi: 10.1038/s41586-021-03362-0. - DOI - PMC - PubMed

Publication types