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Review
. 2024 Jun 13;46(6):5965-5983.
doi: 10.3390/cimb46060356.

MASLD-Related HCC: A Comprehensive Review of the Trends, Pathophysiology, Tumor Microenvironment, Surveillance, and Treatment Options

Yuming Shi  1 , Erfan Taherifard  1 , Ali Saeed  2 , Anwaar Saeed  1   3
Affiliations
Review

MASLD-Related HCC: A Comprehensive Review of the Trends, Pathophysiology, Tumor Microenvironment, Surveillance, and Treatment Options

Yuming Shi et al. Curr Issues Mol Biol. .

Abstract

Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, with MASLD replacing the hepatitis B virus as the primary contributor to new cases of HCC. MASLD-related HCC exhibits distinct characteristics compared to viral HCC, including unique immune cell profiles resulting in an overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, MASLD-related HCC is frequently identified in older age groups and among individuals with cardiometabolic comorbidities. Additionally, a greater percentage of MASLD-related HCC cases occur in noncirrhotic patients compared to those with viral etiologies, hindering early detection. However, the current clinical practice guidelines lack specific recommendations for the screening of HCC in MASLD patients. The evolving landscape of HCC management offers a spectrum of therapeutic options, ranging from surgical interventions and locoregional therapies to systemic treatments, for patients across various stages of the disease. Despite ongoing debates, the current evidence does not support differences in optimal treatment modalities based on etiology. In this study, we aimed to provide a comprehensive overview of the current literature on the trends, characteristics, clinical implications, and treatment modalities for MASLD-related HCC.

Keywords: MASLD; NAFLD; ablation techniques; hepatectomy; hepatocellular carcinoma; immune checkpoint inhibitors; immunotherapy; liver transplantation; metabolic dysfunction-associated steatotic liver disease; nonalcoholic fatty liver disease; population surveillance; protein kinase inhibitors; tumor microenvironment.

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Conflict of interest statement

A.S. (Anwaar Saeed) reports a leadership role with Autem Therapeutics, Exelixis, KAHR Medical, and Bristol-Myers Squibb; consulting or advisory board roles with AstraZeneca, Bristol-Myers Squibb, Merck, Exelixis, Pfizer, Xilio Therapeutics, Taiho, Amgen, Autem Therapeutics, KAHR Medical, and Daiichi Sankyo; institutional research funding from AstraZeneca, Bristol-Myers Squibb, Merck, Clovis, Exelixis, Actuate Therapeutics, the Incyte Corporation, Daiichi Sankyo, Five Prime Therapeutics, Amgen, Innovent Biologics, Dragonfly Therapeutics, Oxford Biotherapeutics, Arcus Therapeutics, and KAHR Medical; and participation as Chair of the Data Safety Monitoring Board for Arcus Therapeutics. The other authors have no relevant financial interests to disclose.

Figures

Figure 1
Figure 1
Overview of liver disease progression leading to HCC in patients with MASLD.
Figure 2
Figure 2
Timeline of the evolution of systemic therapies for patients with advanced HCC and current recommendations in NCCN Guidelines regarding first line and second line of treatment for patients with advanced HCC; order of treatment options does not imply priority.
See this image and copyright information in PMC

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