Impact of Immunonutrition in Patients Undergoing Hepatectomies for Liver Tumors: A Randomized Controlled Phase II Trial

Major hepatectomy remains a cornerstone in the curative management of primary and secondary liver tumors. Despite substantial advances in surgical techniques, anesthesia, and perioperative care, hepatectomy continues to be associated with considerable postoperative morbidity and mortality. Reported morbidity rates range from 22% to 40%, while mortality rates vary between 4% and 11%, largely driven by postoperative infectious complications, liver failure, and systemic inflammatory responses. Optimization of preoperative patient status, particularly nutritional and immune function, has therefore emerged as a critical area of interest to improve postoperative outcomes.

Immunonutrition, defined as nutritional supplementation enriched with specific substrates such as arginine, omega-3 fatty acids, and nucleotides, has demonstrated beneficial effects in patients undergoing major gastrointestinal surgery, pancreatic resections, and liver transplantation. These formulations are thought to modulate immune response, attenuate postoperative inflammation, improve protein synthesis, and enhance wound healing. However, evidence supporting the routine use of immunonutrition in patients undergoing hepatectomy remains limited and inconsistent. Existing meta-analyses suggest reductions in postoperative infectious complications and length of hospital stay, but uncertainty persists regarding its overall clinical benefit, particularly in relation to objective nutritional and immunological markers.

The prognostic nutritional index (PNI), calculated using serum albumin levels and total lymphocyte count, is a validated composite marker reflecting both nutritional and immune status. Multiple studies and meta-analyses have shown that a higher preoperative PNI is associated with improved postoperative outcomes and survival following hepatectomy. Furthermore, recent evidence indicates that inflammatory and nutritional biomarkers, including dynamic changes in albumin-based indices, are strong predictors of postoperative morbidity. These findings suggest that targeted immunonutritional interventions capable of improving PNI may translate into meaningful clinical benefits.

Against this background, the present study is designed to evaluate whether preoperative immunonutrition can improve PNI in patients undergoing major hepatectomy for liver tumors. The central hypothesis is that short-term preoperative immunonutrition leads to a measurable improvement in PNI compared with standard nutritional care.

The aim of the study is to assess the effect of preoperative immunonutrition on the prognostic nutritional index in patients planned for major hepatectomy.