Global prevalence of MAFLD-related hepatocellular carcinoma: A systematic review and meta-analysis

Crane, Harry; Eslick, Guy D.; Gofton, Cameron; Shaikh, Anjiya; Cholankeril, George; Cheah, Mark; Zhong, Jian-Hong; Svegliati-Baroni, Gianluca; Vitale, Alessandro; Kim, Beom Kyung; Ahn, Sang Hoon; Kim, Mi Na; Strasser, Simone; George, Jacob

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Original Article

Global prevalence of MAFLD-related hepatocellular carcinoma: A systematic review and meta-analysis

Harry Crane¹, Guy D. Eslick², Cameron Gofton^1,3, Anjiya Shaikh⁴, George Cholankeril⁵, Mark Cheah⁶, Jian-Hong Zhong⁷, Gianluca Svegliati-Baroni⁸, Alessandro Vitale⁹, Beom Kyung Kim¹⁰, Sang Hoon Ahn¹⁰, Mi Na Kim¹⁰, Simone Strasser¹¹, Jacob George¹

¹Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, New South Wales, Australia
²NHMRC Centre for Research Excellence in Digestive Diseases, Hunter Medical Research Institute (HMRI), The University of Newcastle, Newcastle, New South Wales, Australia
³Department of Gastroenterology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
⁴Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA
⁵Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
⁶Department of Gastroenterology and Hepatology, Singapore General Hospital
⁷Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
⁸Liver Injury and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
⁹Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
¹⁰Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
¹¹AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, Australia

Correspondence :

Jacob George ,
Tel: +61-2-8890-7705, Fax: +61-2-96357582, Email: jacob.george@sydney.edu.au

Received: February 15, 2024 Revised: April 11, 2024 Accepted: April 15, 2024

ABSTRACT

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% 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.
CONCLUSION
MAFLD is common as a sole aetiology, but more so and as a co-factor in mixed-aetiology HCC, supporting the use of a positive diagnostic criteria.

KeyWords: MAFLD, hepatocellular carcinoma, epidemiology, prevalence, dual-aetiology