Harry Crane, Guy D. Eslick, Cameron Gofton, Anjiya Shaikh, George Cholankeril, Mark Cheah, Jian-Hong Zhong, Gianluca Svegliati-Baroni, Alessandro Vitale, Beom Kyung Kim, Sang Hoon Ahn, Mi Na Kim, Simone I Strasser, Jacob George
Clin Mol Hepatol 2024;30(3):436-448. Published online April 16, 2024
Background/Aims The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD).
Methods This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity-specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD, and non-MAFLD HCC.
Results 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% confidence interval [CI] 34.5–63.0%) and 12.4% (95% CI 8.3–17.3%), respectively. In HCC due to chronic hepatitis B, C, and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI 30.2–50.3%), 54.1% (95% CI 40.4–67.6%) and 64.3% (95% CI 52.7–75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC.
Conclusions MAFLD is common as a sole aetiology, but more so as a co-factor in mixed-aetiology HCC, supporting the use of positive diagnostic criteria.
Citations
Citations to this article as recorded by
Astragaloside IV alleviates metabolic associated fatty liver disease by regulating ferroptosis via the SLC7A11/GPX4 pathway Sitong CHEN, Hanying XU, Zipei ZHANG, Xiaonan LI, Xiaolei TANG, Dashi YING Chinese Journal of Analytical Chemistry.2026; 54(2): 100625. CrossRef
Obstructive sleep apnea is associated with greater MASH and significant fibrosis severity in patients with obesity: A prospective clinicopathological study Jia Feng, Wenhui Chen, Zunhao Zhang, Fuqing Zhou, Yang Liu, Zhirui Qiu, Yan Liu, Zhiyong Dong, Cunchuan Wang, Hao Wang, Yi Ma Diabetes, Obesity and Metabolism.2026; 28(3): 1972. CrossRef
Rising burden of MASLD and CKM syndrome in Asia: A decade of trends and future projections Tianqi Duo, Yun Wen, Yu Bian, Yizheng Wang, Xiaofang Zhang, Jin Ju, Yanjie Lu, Zhiguo Wang, Jinghao Wang, Baofeng Yang Metabolism.2026; 178: 156549. CrossRef
Integrating body composition analysis and machine learning for non-invasive identification of metabolic dysfunction-associated fatty liver disease: a large-scale health examination-based study Yaxuan He, Yu Cao, Zekai Chen, Rong Xiang, Fang Wang Scientific Reports.2026;[Epub] CrossRef
Comparison of patients with HCC with and without MASLD after surgical resection Chia-Jung Ho, Hao-Jan Lei, Chun-Ting Ho, Gar-Yang Chau, Shu-Cheng Chou, Elise Chia-Hui Tan, Pei-Chang Lee, Yi-Hsiang Huang, Ying-Ying Yang, Teh-Ia Huo, Ming-Chih Hou, Jaw-Ching Wu, Chien-Wei Su JHEP Reports.2026; 8(4): 101768. CrossRef
Diagnosis and management of metabolic dysfunction-associated steatohepatitis in patients with chronic hepatitis B infection Talal K Bhatti, Joseph K Lim World Journal of Gastroenterology.2026;[Epub] CrossRef
Comparison of the efficacy of transarterial chemoembolization combined with radiofrequency ablation or sintilimab and bevacizumab for unresectable hepatocellular carcinoma Tingting Li, Hongyi Zhao, Chengbin Dong, Yang Song, Miaomiao Li BMC Gastroenterology.2026;[Epub] CrossRef
Integrative Multiomics Analysis Reveals the Ameliorative Effects of Astragalus membranaceus Extract on Metabolic Dysfunction-Associated Steatotic Liver Disease Jiayi An, Yi Li, Zunhan Zhang, Yaru Chang, Guanxiu Xiao Molecules.2026; 31(7): 1120. CrossRef
Association of the Number of Concurrent Metabolic Syndrome Risk Factors with Textbook Outcomes Following Liver Resection for Patients with Hepatocellular Carcinoma: A Multicenter Study Zhan-Cheng Qiu, Jun-Long Dai, Yu Zhang, Fei Xie, Yu Yu, Shu-Sheng Leng, Tian-Fu Wen, Chuan Li Annals of Surgical Oncology.2025; 32(1): 399. CrossRef
Deciphering the roles of neddylation modification in hepatocellular carcinoma: Molecular mechanisms and targeted therapeutics Wenxin Wu, Xuanyi Wang, Ruijie Ma, Shuhong Huang, Hongguang Li, Xinxing Lyu Genes & Diseases.2025; 12(4): 101483. CrossRef
Alterations of Krüppel-like Factor Signaling and Potential Targeted Therapy for Hepatocellular Carcinoma Rongfei Fang, Chunxiu Sha, Qun Xie, Dengfu Yao, Min Yao Anti-Cancer Agents in Medicinal Chemistry.2025; 25(2): 75. CrossRef
Associations of MAFLD subtypes and air pollutants with multi-system morbidity and all-cause mortality: A prospective cohort study Jingyi Zhang, Shanshan Ran, Shengtao Wei, Fei Tian, Lan Chen, Zijun Yang, Ge Chen, Hualiang Lin Ecotoxicology and Environmental Safety.2025; 291: 117893. CrossRef
Global burden and international disparities in NASH-associated liver Cancer: mortality trends (1990–2021) and future projections to 2045 Qilong Nie, Yongwen Jiang, Mingyang Li, Qiuyan Liang, Xiaoai Mo, Tengyu Qiu, Qunfang Jiang, Kaizhou Huang, Youqing Xie, Ying Chen, Xiaojun Ma, Jianhong Li, Kaiping Jiang Frontiers in Public Health.2025;[Epub] CrossRef
Exploring emerging frontiers in hepatology: iLIVER's continuing journey Ming-Da Wang, Xin-Fei Xu, Lei Cai, Tian Yang iLIVER.2025; 4(1): 100148. CrossRef
A review of image guidance and localization methods for liver puncture robots Yongde Zhang, Jiabin Yang, Xuequan Huang, Chuang He Journal of Robotic Surgery.2025;[Epub] CrossRef
Comparative Hepatic Outcomes of SGLT2i or DPP4i Compared to GLP‐1RA in CHB and T2DM Patients Byungyoon Yun, Juyeon Oh, Heejoo Park, Jian Lee, Beom Kyung Kim, Jin‐Ha Yoon Liver International.2025;[Epub] CrossRef
Cardiovascular implications of metabolic dysfunction-associated fatty liver disease and type 2 diabetes mellitus: A meta-analysis Sahana Shetty, Renuka Suvarna, Vanessa Ambrose Fistus, Shivam Modi, Joseph M Pappachan World Journal of Hepatology.2025;[Epub] CrossRef
Characterisation of non-cirrhotic MAFLD-related hepatocellular carcinoma: a retrospective cohort study Shadi Zerehpooshnesfchi, Fatema Safri, Ziyan Pan, Romario Nguyen, Lawrence Yuen, Vincent Lam, Christopher Nahm, Tony Pang, Golo Ahlenstiel, Jacob George, Mohammed Eslam, Liang Qiao Therapeutic Advances in Chronic Disease.2025;[Epub] CrossRef
Case Report: Amelioration of severe metabolic dysfunction-associated steatohepatitis after switching from conventional GLP-1RAs to tirzepatide Yuki Oe, Takashi Omori, Eriko Aimono, Shin Furukawa, Hirohiko Kitakawa, Masatoshi Tateno, Kiyoshi Sakai, Kyu Yong Cho Frontiers in Endocrinology.2025;[Epub] CrossRef
Trends and visualization analysis of research on MASLD-Related hepatocellular carcinoma: a bibliometric analysis Hongkun Yin, Xusheng Zhang, Qi Wang Discover Oncology.2025;[Epub] CrossRef
Overweight and Helicobacter pylori infection: a correlation in metabolic dysfunction-associated fatty liver disease Xu Chen, Jiayue Fu, Kejia Jin, Zixuan Yang, Yidan Qian, Kehan Mei, Yihan Wang, Jialei Min, Yilin Du, Zaisheng Zhu, Shengcun Li Frontiers in Cellular and Infection Microbiology.2025;[Epub] CrossRef
Hemostatic alterations in metabolic dysfunction-associated steatotic liver disease (MASLD) and their link to venous thromboembolism (VTE) David E. González-Mendoza, Francisco Fernández-Nogueira, Misael Uribe, Norberto C. Chávez-Tapia, Natalia Nuño-Lámbarri Thrombosis Research.2025; 253: 109395. CrossRef
Rewriting the MASLD‐associated hepatocellular carcinoma script: Targeting epigenetics and metabolism Chiara Aiello, Eric Felli, Teresa Musarra, Lorenzo Nevi, Annamaria Altomare, Jordi Gracia‐Sancho, Andrea Baiocchini, Simone Carotti International Journal of Cancer.2025; 157(10): 1991. CrossRef
Role of mac-2 binding protein glycosylation isomer in predicting fibrosis in patients with metabolic dysfunction-associated steatotic liver disease Thuy Thi Thu Pham, Dat Tan Ho, Chanh Pham, Hoan Phan, Bieu Phu, Toan Nguyen, Dang Nguyen, Hai Thanh Phan, Khue Minh Nguyen World Journal of Hepatology.2025;[Epub] CrossRef
The triadic relationship between nonalcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease: From molecular mechanisms to clinical management Yuxi Jin, Mohammed Alissa, Ahmed Ezzat Ahmed, Amin A. Al-Doaiss, Naif Asiri, Yasser Assiri, Shahid Ullah Khan, Munir Ullah Khan, Samuel Joseph Current Problems in Cardiology.2025; 50(11): 103170. CrossRef
Exploring the Link Between Irritable Bowel Syndrome and Chronic Diseases: A Narrative Overview Sneha Reddy, Savithri C. Veluri Academic Medicine & Surgery.2025;[Epub] CrossRef
Fibrosis Severity in MASLD Determines the Predictive Value of Lp-PLA2 for Carotid Atherosclerosis in Type 2 Diabetes: A Cross-Sectional Study Junzhao Ye, Rui Song, Xiaorong Gong, Xin Li, Congxiang Shao, Bihui Zhong Biomedicines.2025; 13(10): 2431. CrossRef
Even Lower Alcohol Intake Might Be Harmful for East Asian Males With MASLD Spectrum Byungyoon Yun, Juyeon Oh, Heejoo Park, Jian Lee, Beom Kyung Kim, Jin-Ha Yoon Clinical Gastroenterology and Hepatology.2025;[Epub] CrossRef
Lipid metabolism in cancer cells: Its role in hepatocellular carcinoma progression and therapeutic resistance Tin Lok Wong, Yanshu Kong, Stephanie Ma Hepatology Communications.2025;[Epub] CrossRef
Hepatocellular carcinoma: modern aspects of interdisciplinary management. Part 1. Epidemiology, risk factors, diagnosis Yu.M. Stepanov, N.Yu. Zavhorodnia, O.M. Vlasova GASTROENTEROLOGY.2025; 59(3): 206. CrossRef
Protective effect and mechanisms of puerarin in metabolic dysfunction-associated steatotic liver disease: A systematic review and meta-analysis of animal studies Xiang-yun Zou, Yu-cheng Yang, Xue-han Liu, Wen-ying Qi, Xiao-bin Zao, Xiao-ke Li, Yong’an Ye Pharmacological Research.2025; 222: 108024. CrossRef
A comprehensive bibliometric and visual analysis of tumor-associated macrophages in hepatocellular carcinoma GuanBo Zhang, Gang Li, JinSong Li, Jie Zhang, Zhi Yang, Lin Yang, ShiJie Jiang, ShiFan Zhu, JiaXing Wang Discover Oncology.2025;[Epub] CrossRef
Targeting Ferroptosis: New Insights and Therapeutic Advances in MAFLD Complicating T2DM Fang Yao, Gaochao Wang, Fan Ning, Yanbo Shi Frontiers in Bioscience-Landmark.2025;[Epub] CrossRef
Lean Metabolic Dysfunction‐Associated Steatotic Liver Disease: A Wolf in Sheep's Clothing Xixi Fang, Chenhao Xu, Jun Lu, Runzhou Zhuang, Xiao Xu, Xuyong Wei Cell Biochemistry and Function.2025;[Epub] CrossRef
Glucagon‐Like Peptide‐1 Receptor Agonists and Hepatocellular Carcinoma Prevention: A Meta‐Analysis and Clinical Decision Framework Andrea Dalbeni, Marco Vicardi, Leonardo Antonio Natola, Filippo Cattazzo, Alessandra Auriemma, Rosa Lombardi, Felice Cinque, Luca Dalle Carbonare, Alessandro Mantovani, David Sacerdoti Cancer Medicine.2025;[Epub] CrossRef
Mechanistic roles and intervention strategies involving gut microbiota, amino acid metabolism, and the tumor immune microenvironment in MAFLD-HCC progression Ziwei Guo, Ziang Yao, Xiaohan Chen, Dongjie Wu, Yaqi Ouyang, Yaocun Shen, Yi Wang, Houyan Zhang, Yanping Lu, Wenliang Lv Clinical and Experimental Medicine.2025;[Epub] CrossRef
Splanchnic inflammatory syndrome and the not-so-silent risk of cancer Richard C Semelka MD, Miguel Ramalho MD Gastroenterology & Hepatology: Open access.2024; 15(3): 63. CrossRef
Metabolic dysfunction-associated fatty liver disease is a ubiquitous latent cofactor in viral- and alcoholic-related hepatocellular carcinoma: Editorial on “Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular c Toru Nakamura, Masahito Nakano, Tsubasa Tsutsumi, Keisuke Amano, Takumi Kawaguchi Clinical and Molecular Hepatology.2024; 30(4): 705. CrossRef
Unraveling the epidemiology of metabolic dysfunction-associated liver cancer: Insights from mixed etiologies, regional variations, and gender disparities Gong Feng, Ya-Fei Fan, Ru-Xin Li, Giovanni Targher, Christopher D. Byrne, Ming-Hua Zheng iLIVER.2024; 3(3): 100113. CrossRef
Impact of occult hepatitis B virus infection and high-fat diet on hepatocellular carcinoma development Kun Chen, Chunfeng Qu Hepatoma Research.2024;[Epub] CrossRef
Metabolic (dysfunction)-associated fatty liver disease metrics and contributions to liver research Maito Suoh, Saeed Esmaili, Mohammed Eslam, Jacob George Hepatology International.2024; 18(6): 1740. CrossRef
Metabolic dysfunction-associated fatty liver disease related hepatocellular carcinoma in China: An increasing problem: Letter to the edior on “Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma: A sy Xiangyu Wu, Wenjing Ni, Qianqian Chen, Junping Shi, Jie Li Clinical and Molecular Hepatology.2024; 30(4): 965. CrossRef
Risk of Hepatocellular Carcinoma with Glucagon-like Peptide-1 receptor agonist treatment in patients: a systematic review and meta-analysis Muhammed Shabil, Mahalaqua Nazli Khatib, Suhas Ballal, Pooja Bansal, Balvir S. Tomar, Ayash Ashraf, M. Ravi Kumar, Aashna Sinha, Pramod Rawat, Abhay M. Gaidhane, Sanjit Sah, Afukonyo Shidoiku Daniel, Ambanna Yappalparvi, Ganesh Bushi BMC Endocrine Disorders.2024;[Epub] CrossRef
APASL clinical practice guidelines on systemic therapy for hepatocellular carcinoma-2024 George Lau, Shuntaro Obi, Jian Zhou, Ryosuke Tateishi, Shukui Qin, Haitao Zhao, Motoyuki Otsuka, Sadahisa Ogasawara, Jacob George, Pierce K. H. Chow, Jianqiang Cai, Shuichiro Shiina, Naoya Kato, Osamu Yokosuka, Kyoko Oura, Thomas Yau, Stephen L. Chan, Min Hepatology International.2024; 18(6): 1661. CrossRef
First
Prev
