Retrospective Cohort Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2023; 15(5): 828-842
Published online May 15, 2023. doi: 10.4251/wjgo.v15.i5.828
LipoCol Forte capsules reduce the risk of liver cancer: A propensity score-matched, nationwide, population-based cohort study
Hsiang-Chun Lai, Hung-Jen Lin, Ying-Hsiu Shih, Jen-Wei Chou, Kuan-Wen Lin, 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 40447, Taiwan
Hung-Jen Lin, School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Ying-Hsiu Shih, Management Office for Health Data, China Medical University Hospital, Taichung 40447, Taiwan
Jen-Wei Chou, Department of Internal Medicine, China Medical University Hospital, Taichung 40447, Taiwan
Kuan-Wen Lin, Department of Surgery, China Medical University Hospital, Taichung 40447, 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, Taichung 40447, Taiwan
Sheng-Teng Huang, Cancer Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan
Sheng-Teng Huang, An-Nan Hospital, China Medical University, Tainan 709204, Taiwan
Sheng-Teng Huang, School of Chinese Medicine, China Medical University, Taichung 40447, Taiwan
Author contributions: Lai HC contributed to the conceptualization, methodology, and writing-original draft; Lin HJ contributed to the resources, investigation, validation, and editing; Shih YH contributed to the software, formal analysis, visualization; Chou JW, Lin KW, and Jeng LB contributed to the resources and supervision; Huang ST contributed to the methodology, writing-reviewing and editing, project administration, and funding acquisition.
Supported by the Ministry of Science and Technology of Taiwan, No. NSTC111-2320-B-039-025; and China Medical University Hospital, No. DMR-111-013 and No. DMR-111-195.
Institutional review board statement: The study was approved by the Research Ethics Committee of China Medical University Hospital [CMUH109-REC2-031(CR-2)] and was in compliance with the Declaration of Helsinki.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The datasets generated for this study are available on request to the corresponding author.
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, Department of Chinese Medicine, China Medical University Hospital, No. 2 Yude Road, North District, Taichung 40447, Taiwan. sheng.teng@yahoo.com
Received: January 25, 2023
Peer-review started: January 25, 2023
First decision: February 28, 2023
Revised: March 3, 2023
Accepted: April 19, 2023
Article in press: April 19, 2023
Published online: May 15, 2023
Abstract
BACKGROUND

Liver cancer is among the top five most common cancers globally. Lipid-lowering drugs such as statins can lower the risk of liver cancer, but may also cause liver damage. LipoCol Forte capsules (LFC), a red yeast rice product, have demonstrated significant antihypercholesterolemic effects and a good safety profile in clinical studies.

AIM

To evaluate whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort study.

METHODS

We used data from Taiwan’s National Health Insurance Research Database, which includes electronic medical records for up to 99.99% of Taiwan’s population. LFC users and LFC non-users were matched 1:1 by propensity scores between January 2010 and December 2017. All had follow-up data for at least 1 year. Statistical analyses compared demographic distributions including sex, age, comorbidities, and prescribed medications. Cox regression analyses estimated adjusted hazard ratios (aHRs) after adjusting for potential confounders.

RESULTS

We enrolled 33231 LFC users and 33231 non-LFC users (controls). No significant differences between the study cohorts were identified regarding comorbidities and medications [standardized mean difference (SMD) < 0.05]. At follow-up, the overall incidence of liver cancer was significantly lower in the LFC cohort compared with controls [aHR 0.91; 95% confidence interval (CI): 0.86-0.95; P < 0.001]. The risk of liver cancer was significantly reduced in both females (aHR 0.87; 95%CI: 0.8-0.94; P < 0.001) and males (aHR 0.93; 95%CI: 0.87-0.98; P < 0.01) in the LFC cohort compared with their counterparts in the non-LFC cohort. The antitumor protective effects applied to patients with comorbidities (including hypertension, ischemic stroke, diabetes mellitus, hyperlipidemia, hepatitis B infection and hepatitis C infection). Those using LFC for more than 84 drug days had a 0.64-fold lower risk of liver cancer compared with controls (P < 0.001). Compared with controls, the risk of developing liver cancer in the LFC cohort progressively decreased over time; the lowest incidence of liver cancer occurred in LFC users followed-up for more than 6 years (27.44 vs 31.49 per 1,000 person-years; aHR 0.75; 95%CI: 0.68-0.82; P < 0.001).

CONCLUSION

This retrospective cohort study indicates that LFC has a significantly protective effect on lowering the risk of liver cancer, in a dose-dependent and time-dependent manner.

Keywords: LipoCol Forte capsules, Hyperlipidemia, Liver cancer, Hepatocellular carcinoma, Retrospective cohort study, Taiwan National Health Insurance Research Database

Core Tip: LipoCol Forte capsules (LFC), a red yeast rice product, have lipid-lowering effects and good safety reports. Lipid-lowering therapies such as statins can lower the risk of liver cancer, but may also cause liver damage. We evaluated whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort study. The LFC cohort had a 9% lower incidence of liver cancer compared with controls; this lower risk was dose-dependent and time-dependent, with a 0.64-fold lower risk found in those using LFC for more than 84 drug days. The lowest incidence of liver cancer occurred in LFC users followed-up for more than 6 years.