MAFLD: an optimal framework for understanding liver cancer phenotypes

Area of Science:

• Hepatology and Oncology
• Metabolic Syndrome Research

Background:

• Hepatocellular carcinoma (HCC) mortality remains high, with increasing incidence despite progress against viral factors.
• Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease, paralleling obesity and diabetes epidemics.
• MAFLD significantly contributes to HCC rise, both independently and synergistically with other liver conditions.

Purpose of the Study:

• To review current data on the epidemiology, clinical characteristics, and outcomes of MAFLD-related HCC.
• To discuss controversies in screening and treatment response for MAFLD-related HCC.
• To explore emerging concepts within the MAFLD paradigm, including non-overlapping groups, dual etiologies, and distinct sub-phenotypes.

Main Methods:

• Comprehensive literature review of epidemiological studies, clinical data, and treatment response analyses related to MAFLD and HCC.
• Analysis of mechanisms underlying MAFLD-related HCC, including systemic metabolic dysregulation and interacting factors.
• Examination of distinct clinical presentations and challenges in surveillance for MAFLD-related HCC.

Main Results:

• MAFLD is a primary driver of increasing HCC incidence, frequently presenting in non-cirrhotic livers.
• Mechanisms involve complex interplay of metabolic dysregulation, environmental, genetic, immune, and microbial factors.
• MAFLD-related HCC poses unique challenges for surveillance and has a controversial response to immune-checkpoint therapy.

Conclusions:

• MAFLD represents a critical, growing factor in hepatocellular carcinoma etiology and incidence.
• Distinct clinical features of MAFLD-related HCC necessitate tailored surveillance and management strategies.
• Further research into MAFLD sub-phenotypes and treatment responses is crucial for improving patient outcomes.