Retrospective Cohort Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2024; 16(3): 716-731
Published online Mar 15, 2024. doi: 10.4251/wjgo.v16.i3.716
Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management
Hsiang-Chun Lai, Ju-Chien Cheng, Hei-Tung Yip, Long-Bin Jeng, Sheng-Teng Huang
Hsiang-Chun Lai, Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404328, Taiwan
Ju-Chien Cheng, Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan
Hei-Tung Yip, Management Office for Health Data, China Medical University Hospital, Taichung 404327, Taiwan
Long-Bin Jeng, Organ Transplantation Center, China Medical University Hospital, Taichung 40447, Taiwan
Sheng-Teng Huang, Department of Chinese Medicine, China Medical University Hospital; School of Chinese Medicine, China Medical University, Taichung 40447, Taiwan
Author contributions: Lai HC contributed to conceptualization, methodology, writing - original draft; Cheng JC contributed to resources, investigation, validation, editing; Yip HT contributed to software, formal analysis, visualization; Jeng LB contributed to resources, supervision, editing; Huang ST contributed to methodology, writing-reviewing and editing, project administration, funding acquisition.
Supported by the National Science and Technology Council of Taiwan, No. NSC112-2320-B-039-045-; China Medical University Hospital, No. DMR-111-013, No. DMR-111-195, No. DMR-112-004 and No. DMR-112-177; and Department of Chinese Medicine and Pharmacy and Ministry of Health and Welfare, No. MOHW-112-CMC-03.
Institutional review board statement: This study was approved by the Institutional Review Board of China Medical University Hospital Research Ethics Committee, No. CMUH109-REC2-031 (CR-3).
Informed consent statement: In the study, all available data were extracted from NHIRD. All records and personal information were anonymized prior to analysis, thus the requirement for written informed consent was waived.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets generated for this study are available upon request by the corresponding authors at sheng.teng@yahoo.com.
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: Sheng-Teng Huang, MD, PhD, Doctor, Professor, Department of Chinese Medicine, China Medical University Hospital; School of Chinese Medicine, China Medical University, No. 2 Yude Road, North District, Taichung 40447, Taiwan. sheng.teng@yahoo.com
Received: October 10, 2023
Peer-review started: October 10, 2023
First decision: December 6, 2023
Revised: December 31, 2023
Accepted: February 1, 2024
Article in press: February 1, 2024
Published online: March 15, 2024
Processing time: 153 Days and 18.1 Hours
Abstract
BACKGROUND

Type 2 diabetes mellitus (DM) is an independent risk factor for hepatocellular carcinoma (HCC), while insulin is a potent mitogen. Identifying a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for researchers.

AIM

To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control.

METHODS

We used data acquired from the Taiwanese National Health Insurance research database between 2000 and 2017. We identified patients with DM who were prescribed insulin for > 3 months. The herb user group was further defined as patients prescribed herbal medication for DM for > 3 months per annum during follow-up. We matched the herb users to nonusers at a 1:3 ratio according to age, sex, comorbidities and index year by propensity score matching. We analyzed HCC incidence, HCC survival rates, and the herbal prescriptions involved.

RESULTS

We initially enrolled 657144 DM patients with regular insulin use from 2000 to 2017. Among these, 46849 patients had used a herbal treatment for DM, and 140547 patients were included as the matched control group. The baseline variables were similar between the herb users and nonusers. DM patients with regular herb use had a 12% decreased risk of HCC compared with the control group [adjusted hazard ratio (aHR) = 0.88, 95%CI = 0.80–0.97]. The cumulative incidence of HCC in the herb users was significantly lower than that of the nonusers. Patients with a herb use of > 5 years cumulatively exhibited a protective effect against development of HCC (aHR = 0.82, P < 0.05). Of patients who developed HCC, herb users exhibited a longer survival time than nonusers (aHR = 0.78, P = 0.0001). Additionally, we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the constituents. Our analysis indicated that Astragalus propinquus (Huang Qi) plus Salvia miltiorrhiza Bunge (Dan Shen), and Astragalus propinquus (Huang Qi) plus Trichosanthes kirilowii Maxim. (Tian Hua Fen) were the most frequent combination of single herbs. Meanwhile, Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and formulas.

CONCLUSION

This large-scale retrospective cohort study reveals that herbal medicine may decrease HCC risk by 12% in DM patients with regular insulin use.

Keywords: Hepatocellular carcinoma; Diabetes mellitus; Insulin; Herb; Taiwanese National health insurance research database

Core Tip: Type 2 diabetes mellitus (DM) is an independent risk factor for hepatocellular carcinoma (HCC), while insulin is a potent mitogen. In this propensity-score-matched population-based cohort study, we investigated whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control. DM patients with regular herb use had a 12% decreased risk of HCC compared to the control group. The cohort with herb use of > 5 years cumulatively exhibited a protective effect against development of HCC. Moreover, among patients who developed HCC, herb users exhibited a longer survival time than non-users (adjusted hazard ratio = 0.78).