Analysis of prognosis and background liver disease in non-advanced hepatocellular carcinoma in two decades

Shun Kaneko, Yasuhiro Asahina, Miyako Murakawa, Seishin Azuma, Kento Inada, Tomohiro Mochida,Keiya Watakabe, Taro Shimizu, Jun Tsuchiya, Masato Miyoshi,F ukiko Kawai-Kitahata, Sayuri Nitta, Marie Takahashi, Tomoyuki Fujioka, Mitsuhiro Kishino, Tatsuhiko Anzai, Sei Kakinuma, Mina Nakagawa, Ryuichi Okamoto

Antiviral hepatitis and systemic therapies for hepatocellular carcinoma (HCC) remarkably progressed in the recent 10 years. This study aimed to reveal the actual transition and changes in the prognosis and background liver disease in non-advanced HCC in the past 20 years.

Liver cancer is the fourth leading cause of cancer-related death worldwide, and the World Health Organization estimates that more than 1 million people will die from the disease by 2030. Hepatocellular carcinoma (HCC) is leading cancer, accounting for 90% of liver cancer, and remains a global threat [1, 2]. The annual report of the national cancer institute reported the increased incidence rate of liver cancer in females [3].

Antiviral hepatitis therapy remarkably progressed, especially for hepatitis B and C. The effectiveness of direct-acting antivirals (DAAs) in eradicating the hepatitis C virus (HCV) is firmly established and is one of the greatest successes of medical therapeutics in the last 20 years [4].

Patients with HCC were retrospectively enrolled from 705 patients who were diagnosed at the Tokyo Medical and Dental University (TMDU) Hospital from February 2002 to February 2022. HCC diagnosis was based on pathologically proven HCC or radiologic findings, such as typical tumor arterial enhancement followed by a washout pattern in the portal venous phase or the equilibrium phase on dynamic computed tomography (CT) or magnetic resonance imaging (MRI), following the criteria of practice guidelines [16, 17, 19]. Angiography which included CT during hepatic arteriography and arterial portography was performed mainly prior to 2008 (EOB-MRI was not available) to obtain a definitive HCC diagnosis or in the course of TACE treatment.

This study analyzed 566 patients who were diagnosed with HCC through AG from February 2002 to February 2022. Patient characteristics were presented in Table 1. The median age was 72 (range: 30–95) years. Regarding background liver disease etiology, 64 (11.3%), 324 (57.2%), 95 (16.8%), 24 (4.2%), and 59 (10.4%) patients had HBV, HCV, alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), and others. The median ALBI score was −2.477. The number of males was 382 (67.5%), and C-P grades A and B were found in 452 (79.9%) and 109 (19.3%) patients, respectively. BCLC stages 0/A (early) and B (intermediate) were found in 404 (71.4%) and 162 (28.6%) patients, respectively.

This study revelated the actual transition and changes in the prognosis and background liver disease of non-advanced HCC in the past 2 decades. Patients with HCC were older, with lower ALBI, better liver function, lower AFP, and more antiviral therapy for viral hepatitis as time goes from period I to Ⅱ. Viral hepatitis (HBV and HCV) decreased and non-viral hepatitis increased as the etiology of HCC (Table 1).

The prognostic factors included age and ALBI (Table 4A), and were more dependent on the status of the background liver disease rather than the tumor status in BCLC stage 0/A. Some competing factors, such as older age, antiviral therapy, and better liver function, were observed through the transition from periods I to Ⅱ.

Citation: Kaneko S, Asahina Y, Murakawa M, Azuma S, Inada K, Mochida T, et al. (2024) Analysis of prognosis and background liver disease in non-advanced hepatocellular carcinoma in two decades. PLoS ONE 19(3): e0297882.

Editor: Satoru Hagiwara, Kindai University Faculty of Medicine, JAPAN

Received: July 7, 2023; Accepted: January 3, 2024; Published: March 7, 2024

Copyright: © 2024 Kaneko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The datasets generated and/or analyzed during the current study are available on reasonable request because of ethical reason. The point of contact is need for Ethical Committee of TMDU Hospital ( because the data of this study contains sensitive patient information.

Funding: This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Numbers 23fk0210106, 23fk0210104, 23fk0210113, 23fk0210102, 23fk0310501, 22ama221302, 23fk0210118, 23fk0210126, 23fk0210123 and Grant-in-Aid for Scientific Research (KAKENHI grant numbers 22K20910, 22K08005, 21K15942, 21K07939, 21K07977, 21H02896, 21K19476, 22H03054, 23K15066). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: NO authors have competing interests.