What is the Origin of MASLD?

The term was recently introduced by international liver disease societies to reflect a more accurate and positive-framing understanding of the disease's underlying etiology. The shift from "Non-Alcoholic" to "Metabolic Dysfunction-Associated" explicitly recognizes that the primary driver of this pathology is a systemic metabolic derangement, making the diagnosis more precise and aligning it with the pathophysiological mechanisms. This renaming aids in global communication and research efforts.

What is the Mechanism of MASLD?

The core mechanism, often referred to as the "multiple-hit" hypothesis, begins with peripheral insulin resistance, leading to excessive delivery of free fatty acids to the liver and increased de novo lipogenesis. This fat accumulation overwhelms the hepatocyte's capacity for lipid processing, leading to oxidative stress, mitochondrial dysfunction, and the release of inflammatory cytokines. The resulting hepatic inflammation can progress to Metabolic Dysfunction-Associated Steatohepatitis (MASH) and eventually cirrhosis, creating a profound hormonal environment that further exacerbates insulin resistance.

MASLD

Meaning

MASLD stands for Metabolic Dysfunction-Associated Steatotic Liver Disease, a newly established nomenclature replacing the former term NAFLD (Non-Alcoholic Fatty Liver Disease). This chronic liver condition is characterized by the accumulation of excess fat (steatosis) in the liver cells, not primarily caused by excessive alcohol consumption, and is fundamentally linked to metabolic dysfunction. Clinically, MASLD is strongly associated with insulin resistance, obesity, type 2 diabetes, and dyslipidemia, highlighting the liver’s central role in metabolic-endocrine crosstalk.

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What Do Elevated Liver Enzymes Indicate during Hormone Optimization?

Elevated liver enzymes on hormone therapy often signal the liver's metabolic adaptation to processing new hormones.

∞ IGF-1
∞ Sermorelin
∞ Metabolic Adaptation

HRTioAugust 3, 2025

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