Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 27, 2022; 14(7): 1480-1494
Published online Jul 27, 2022. doi: 10.4254/wjh.v14.i7.1480
Pre-sarcopenia and Mac-2 binding protein glycosylation isomer as predictors of recurrence and prognosis of early-stage hepatocellular carcinoma
Masato Nakai, Kenichi Morikawa, Shunichi Hosoda, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Masatsugu Ohara, Takuya Sho, Goki Suda, Koji Ogawa, Naoya Sakamoto
Masato Nakai, Kenichi Morikawa, Shunichi Hosoda, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Masatsugu Ohara, Takuya Sho, Goki Suda, Koji Ogawa, Naoya Sakamoto, Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
Author contributions: Nakai M and Morikawa K planned the contents of manuscript; Nakai M, Morikawa K, Hosoda S, Yoshida S, Kubo A, Tokuchi Y, Kitagataya T, Yamada R, Ohara M, Sho T, Suda G, Ogawa K, and Sakamoto N collected the data; Nakai M and Morikawa K analyzed the data and drafted the manuscript; all authors revised the manuscript.
Institutional review board statement: The study protocol was approved by the Institutional Ethics Committee of Hokkaido University (IRB no. 015-1412) and conformed to the ethical guidelines of the Declaration of Helsinki.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kenichi Morikawa, MD, PhD, Associate Professor, Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Kita 15 Nishi 7, Kita-ku, Sapporo 0608638, Hokkaido, Japan. kenichi.morikawa@med.hokudai.ac.jp
Received: February 25, 2022
Peer-review started: February 25, 2022
First decision: April 8, 2022
Revised: April 20, 2022
Accepted: June 22, 2022
Article in press: June 22, 2022
Published online: July 27, 2022
Processing time: 152 Days and 7.8 Hours
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is prone to recurrence, even if cured at an early stage. In recent years, many studies have demonstrated that sarcopenia is a poor prognostic factor in patients with chronic liver disease and HCC, because it is related to frailty, loss of function, and low quality of life. Pre-sarcopenia is defined as muscle volume loss without muscle power loss and is a poor prognostic factor in the elderly population. In addition, the usefulness of the Mac-2 binding protein glycosylation isomer (M2BPGi), or Wisteria floribunda agglutinin-positive M2BP, which was first reported as a fibrosis marker in hepatitis C virus (HCV) patients, to treat HCC has recently attracted attention.

Research motivation

The M2BPGi, a fibrosis marker in various liver diseases, is reportedly a prognostic marker in patients with HCC who underwent hepatectomy. In recent years, many studies have demonstrated that sarcopenia is a poor prognostic factor in patients with chronic liver disease and HCC, because it is related to frailty, loss of function, and low quality of life. Sarcopenia is diagnosed using both muscle power loss and muscle volume loss. Pre-sarcopenia is defined as muscle volume loss without muscle power loss and is a poor prognostic factor in the elderly population.

Research objectives

To investigate the usefulness of pre-sarcopenia, M2BPGi, and M2BP as recurrence and prognostic factors in patients who underwent RFA for early-stage HCC.

Research methods

In this study, 202 patients underwent radiofrequency ablation (RFA) for primary HCCs. Of these, 160 cases were classified as BCLC stage 0 or A, and the data were analyzed. Eighty-three patients were classified into the HCV-positive group, and 77 patients were classified into the HCV-negative group.

Research results

In HCV-positive patients, only des-γ-carboxy-prothrombin (DCP) ≥ 23 mAU/mL was a significant poor prognostic factor affecting survival after RFA. In HCV-negative patients, M2BPGi ≥ 1.86 cutoff index was significantly associated with tumor recurrence, but M2BP was not. M2BPGi ≥ 1.86 cutoff index (hazard ratio, 4.89; 95% confidence interval: 1.97-12.18; P < 0.001) and pre-sarcopenia (hazard ratio, 3.34, 95% confidence interval: 1.19-9.37; P = 0.022) were independent significant poor prognostic factors in HCV-negative patients.

Research conclusions

In HCV-negative patients with primary HCC treated with RFA, lower M2BPGi contributed to a lower tumor recurrence rate and longer survival period. Pre-sarcopenia contributed to the poor prognosis independently in HCV-negative patients.

Research perspectives

In the near future, almost all HCVs will be eradicated by DAA treatment. Almost no HCC cases were derived from the current HCV infection. Pre-sarcopenia and M2BPGi, but not M2BP, might be useful tools to predict survival in early-stage HCC in the era of HCV eradication.