Metabolic Associated Fatty Liver Disease (MAFLD), a terminology recently proposed to better reflect the current knowledge of fatty liver diseases associated with metabolic syndrome (MS), is an emerging chronic liver disease. MALFD encompasses a wide spectrum of liver injury, from steatosis to steato-hepatitis that may progress to fibrosis/cirrhosis, and ultimately hepatocellular carcinoma (HCC). Given the increasing prevalence of MS, MAFLD is becoming the leading risk factor of HCC worldwide.
Importantly, liver carcinogenesis associated with MAFLD is somehow peculiar, as, by contrast to other risk factors for chronic liver diseases, mostly hepatitis C virus infection or chronic alcohol consumption, may arise in absence of underlying cirrhosis in a significant proportion of patients (up to 40% in some studies). Such a picture suggests the involvement of specific oncogenic mechanisms. Although the molecular mechanisms are not fully elucidated, some of them may play a role, including low-grade chronic inflammation related to obesity and MS, hepatic metabolic reprogramming, dysregulated autophagy, gut microbiota, etc. Some specificities are also observed in HCC developed in patients with MS in the morphological and molecular aspects. For example, a specific HCC subtype (“steatohepatitic HCC”), characterized by morphological hallmarks recapitulating NASH picture, is more often observed in this context.
Finally, prognosis of patients with HCC associated with MS does not appear to be very different compared to those with HCC related to hepatitis C and alcohol-related liver diseases.
1. Jean-Charles Nault Service d'Hepatologie, Hopital Jean Verdier, Hopitaux universitaires Paris-Seine-Saint-Denis, Assistance publique Hopitaux de Paris, Bondy, France.
2. Helen Louise Reeves Northern Institute for Cancer Research, The Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
3. Michael Torbenson Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, USA.
4. Amon Asgharpour Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, Institute of liver medicine at Mount Sinai, New York, USA.
5. Nicolas Goossens Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, Institute of liver medicine at Mount Sinai, New York, USA.
6. François Cauchy Department of Hepatobiliary and Liver transplantation, Hospital Beaujon, Clichy, France.
7. Olivier Soubrane Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, Clichy, France.
8. Valérie Paradis Department of Pathology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France.
The list is arranged in no particular order and being updated.
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