Author information

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.

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.