Essential phospholipids in the treatment of metabolic dysfunction-associated steatotic liver disease: From molecular mechanisms to clinical efficacy (a literature review)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an umbrella term encompassing a spectrum of conditions ranging from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, and cirrhosis associated with systemic metabolic dysfunction. The prevalence of MASLD continues to rise steadily and is closely linked to cardiovascular morbidity and mortality, making it one of the most relevant chronic noncommunicable diseases. This review analyzes data from clinical trials on the efficacy of essential phospholipids (EPL) as monoand adjuvant therapy for MASLD, taking into account the characteristics of their mechanisms of action, effects, and potential for pharmacological enhancement. The review was conducted using a narrative (non-systematic) approach based on a literature search performed in Russian and international specialized databases and clinical trial registries. EPL and their principal active component, 1,2-dilinoleoylphosphatidylcholine, enhance the stability and fluidity of cell membranes, support the transmembrane processes, reduce the severity of mitochondrial dysfunction and oxidative stress, inhibit lipogenesis, facilitate bile acid efflux, slow the activation of hepatic stellate cells, and reduce local inflammation and hepatocyte apoptosis. In addition to their own hepatotropic activity, EPL may also act as a pharmacological enhancer by increasing bioavailability, prolonging systemic circulation, and potentiating the effects of other drugs. When used as monotherapy for MASLD/MASH, EPL exert an anti-cytolytic effect, may reduce hepatic steatosis (assessed by ultrasonography), and improve lipid profile parameters; however, the available evidence is limited by the small statistical power and design flaws of the clinical trials. Special attention has been directed toward the potential use of EPL as part of combination pharmacotherapy for MASLD in comorbid patients. As evidenced by clinical trials, the addition of EPL to standard treatment regimens can enhance therapeutic efficacy regarding morphological liver changes, marker enzyme levels, lipid metabolism parameters, and patients’ quality of life.

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