Keywords
Cardiovascular disease
Hepatocellular carcinoma
FIB-4 index
Metabolic syndrome
Steatotic liver
Systemic inflammation
Resmetirom
How to Cite
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has surpassed viral hepatitis as the primary driver of chronic liver disease globally. While traditionally viewed through the lens of hepatic progression, its clinical trajectory is increasingly defined by extrahepatic complications.
Objective: This narrative review evaluates MASLD as a manifestation of systemic metabolic failure, specifically analyzing its role in accelerating cardiovascular dysfunction and extrahepatic carcinogenesis—the two principal causes of mortality in this population.
Methods: A comprehensive literature synthesis was conducted from 2020 to December 2025, using databases including PubMed, Scopus, and the Egyptian Knowledge Bank (EKB) to identify high-impact studies and international guidelines.
Results: The pathophysiology involves a metabolic cascade whereby hepatic lipid accumulation and insulin resistance trigger systemic inflammatory signaling. Disrupted lipid handling and genetic determinants promote pro-atherogenic and pro-oncogenic environments. The review advocates a transition to risk-stratified approaches using noninvasive biomarkers, such as the FIB-4 index.
Conclusion: Addressing the bidirectional relationship between hepatic steatosis and systemic comorbidities requires a multidisciplinary therapeutic strategy. This framework provides a basis for early intervention to reduce the burden of cardiovascular events and malignancy among patients with MASLD.
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