MAFLD: an optimal framework for understanding liver cancer phenotypes

Abstract

Hepatocellular carcinoma has a substantial global mortality burden which is rising despite advancements in tackling the traditional viral risk factors. Metabolic (dysfunction) associated fatty liver disease (MAFLD) is the most prevalent liver disease, increasing in parallel with the epidemics of obesity, diabetes and systemic metabolic dysregulation. MAFLD is a major factor behind this sustained rise in HCC incidence, both as a single disease entity and often via synergistic interactions with other liver diseases. Mechanisms behind MAFLD-related HCC are complex but is crucially underpinned by systemic metabolic dysregulation with variable contributions from interacting disease modifiers related to environment, genetics, dysbiosis and immune dysregulation. MAFLD-related HCC has a distinct clinical presentation, most notably its common occurrence in non-cirrhotic liver disease. This is just one of several major challenges to effective surveillance programmes. The response of MAFLD-related HCC to immune-checkpoint therapy is currently controversial, and is further complicated by the high prevalence of MAFLD in individuals with HCC from viral aetiologies. In this review, we highlight the current data on epidemiology, clinical characteristics, outcomes and screening controversies. In addition, concepts that have arisen because of the MAFLD paradigm such as HCC in MAFLD/NAFLD non-overlapping groups, dual aetiology tumours and MAFLD sub-phenotypes is reviewed.

Chronic stress alters hepatic metabolism and thermodynamic respiratory efficiency affecting epigenetics in C57BL/6 mice

“… 3 , 4 , 5 The elevated cC18:2 levels observed in our study are in line with those in NAFLD. 41 We previously found an increase in liver fat after the recovery phase in our Cvs model, but not acutely following stress. 27 The gene expression data indicate suppressed lipid synthesis during the longitudinal observation of Cvs.…”

Obesity and harmful alcohol consumption are predictors for advanced liver disease in the disease management program for type 2 diabetes

“… 19 Metabolic risk factors are also known to augment the risk of progression independent of the liver disease etiology. 25 Although a previous analysis showed a lower prevalence of fibrosis and liver cirrhosis in T2DM, participants with other liver disease etiologies than MASLD have been excluded. 19 However, the role of harmful alcohol consumption in liver disease cannot be underestimated and even moderate alcohol intake was associated with a higher risk of fibrosis progression and cirrhosis‐related complications in those identified with MASLD.…”

Body Composition in Chronic Liver Disease

“…Although NAFLD has served as an anchor point for clinical practice and trials, substantial concerns have been raised about its use due to the inherent drawbacks of being exclusionary and stigmatizing, prompting a search for new nomenclature. In April 2020, distinguished hepatologists from all over the world met and discussed the new disease concept of metabolic dysfunction-associated fatty liver disease (MAFLD) [38], which is now becoming more common in the medical community [39]. The diagnostic criteria for MAFLD are FL and one or more of the following three conditions (with or without a history of alcohol or other causes of liver disease): (1) overweight and obesity (BMI ≥ 23 kg/m 2 in Japanese);…”