Liver fibrosis and MAFLD: the exploration of multi-drug combination therapy strategies

Qingfu Dong; Haolin Bao; Jiangang Wang; Wujiang Shi; Xinlei Zou; Jialin Sheng; Jianjun Gao; Canghai Guan; Haoming Xia; Jinglin Li; Pengcheng Kang; Yi Xu; Yunfu Cui; Xiangyu Zhong

doi:10.3389/fmed.2023.1120621

Liver fibrosis and MAFLD: the exploration of multi-drug combination therapy strategies

Front Med (Lausanne). 2023 Apr 20:10:1120621. doi: 10.3389/fmed.2023.1120621. eCollection 2023.

Authors

Qingfu Dong¹, Haolin Bao¹, Jiangang Wang², Wujiang Shi¹, Xinlei Zou¹, Jialin Sheng¹, Jianjun Gao¹, Canghai Guan¹, Haoming Xia¹, Jinglin Li¹, Pengcheng Kang¹, Yi Xu^{1

3

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10}, Yunfu Cui¹, Xiangyu Zhong¹

Affiliations

¹ Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
² Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
³ Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.
⁴ Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, Xiamen, Fujian, China.
⁵ Jiangsu Province Engineering Research Center of Tumor Targeted Nano Diagnostic and Therapeutic Materials, Yancheng Teachers University, Yancheng, Jiangsu, China.
⁶ Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, China.
⁷ Key Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.
⁸ State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, China.
⁹ Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
¹⁰ Key Laboratory of Intelligent Pharmacy and Individualized Therapy of Huzhou, Department of Pharmacy, Changxing People's Hospital, Changxing, Zhejiang, China.

Abstract

In recent years, the prevalence of metabolic-associated fatty liver disease (MAFLD) has reached pandemic proportions as a leading cause of liver fibrosis worldwide. However, the stage of liver fibrosis is associated with an increased risk of severe liver-related and cardiovascular events and is the strongest predictor of mortality in MAFLD patients. More and more people believe that MAFLD is a multifactorial disease with multiple pathways are involved in promoting the progression of liver fibrosis. Numerous drug targets and drugs have been explored for various anti-fibrosis pathways. The treatment of single medicines is brutal to obtain satisfactory results, so the strategies of multi-drug combination therapies have attracted increasing attention. In this review, we discuss the mechanism of MAFLD-related liver fibrosis and its regression, summarize the current intervention and treatment methods for this disease, and focus on the analysis of drug combination strategies for MAFLD and its subsequent liver fibrosis in recent years to explore safer and more effective multi-drug combination therapy strategies.

Keywords: cirrhosis; drug combination therapy; liver fibrosis; metabolic-associated fatty liver disease (MAFLD); non-alcoholic steatohepatitis (NASH).

Publication types

Review

Grants and funding

This study was supported by the National Natural Science Foundation of China (82270599 and 81902431), the Natural Science Foundation of Heilongjiang Province (LH2022H018), the Hong Kong Scholars Program (XJ2020012), the Marshal Initiative Funding of Harbin Medical University (HMUMIF-22008), the Beijing Xisike Clinical Oncology Research Foundation (YYoung2022-0188), the Medjaden Academy & Research Foundation for Young Scientists (MJR20220903), the Opening Research Fund of Key Laboratory of Gastrointestinal Cancer, Fujian Medical University, Ministry of Education (FMUGIC-202203), the Opening Project of Key Laboratory of Environment and Health, Ministry of Education (2022GWKFJJ01), the Opening Project of Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University (XMMC-FCTM202205), the Opening Project of Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province (KFJJ-2022002), the Opening Project of Guangxi Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer (GXEKL202204), the Opening Project of Jiangsu Province Engineering Research Center of Tumor Targeted Nano Diagnostic and Therapeutic Materials (JETNM202210), the Opening Project of Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medicial University (2022-449), the Opening Project of the State Key Laboratory of Chemical Oncogenomics, Thematic Research Support Scheme of State Key Laboratory of Liver Research, The University of Hong Kong (SKLLR/TRSS/2022/08), Opening Project of Key Laboratory of Intelligent Pharmacy and Individualized Therapy of Huzhou & Changxing Anti-cancer Association (NZKF-20230203), and Opening Project of Fujian Provincial Key Laboratory of Innovative Drug Target Research (FJ-YW-2022KF03).