Effects of Nutritional Supplementation With Eicosapentaenoic Acid (EPA) on Body Composition and Systemic Pro-inflammatory and Pro-resolving Mediators in Patients Diagnosed With Unresectable Hepatocellular Carcinoma.

Cancer-associated cachexia is a debilitating and potentially life-threatening syndrome characterized by progressive loss of body weight, skeletal muscle, and adipose tissue, leading to functional impairment and reduced response to oncologic therapy. It is driven in part by systemic inflammation and increased pro-inflammatory cytokines, and it cannot always be reversed with conventional support.

Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid (PUFA), has anti-inflammatory properties and is rapidly incorporated into cell membranes, modulating lipid mediator pathways. EPA supplementation may help to attenuate systemic inflammation, alleviate cachexia symptoms, and promote the production of specialized pro-resolving mediators. A daily dose of 3 grams appears sufficient to achieve maximal incorporation into cell membranes without significant adverse events.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, with most patients diagnosed at advanced stages. Cachexia is common in advanced HCC and contributes to functional decline, increased treatment toxicity, and poorer outcomes. Preclinical studies suggest that omega-3 PUFAs may also exert anti-tumor effects through modulation of COX-2 and Wnt/beta-catenin signaling pathways.

For these reasons, in this proposal, the investigators aim to determine wheter supplementation with EPA in combination with chemotherapy will modify the blood profile of pro-inflammatory and pro-resolving mediators, promoting the resolution of inflammation associated with HCC, and, in turn, mitigate muscle mass loss during oncologic treatment.