Association of baseline protein–energy malnutrition with mortality and healthcare utilization in patients with hepatocellular carcinoma treated with VEGF-based systemic therapy.

Abstract

e16166 Background: Patients with hepatocellular carcinoma (HCC) frequently have advanced liver disease and frailty at the time of systemic therapy initiation. Protein–energy malnutrition (PEM) is common in this population; however, whether PEM reflects acute illness at treatment initiation or is associated with persistent vulnerability after therapy begins remains unclear. We evaluated the association between baseline PEM and early clinical outcomes after excluding deaths and events within the first 30 days of VEGF-based therapy. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults with HCC treated with VEGF-based systemic therapies (bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib, or ramucirumab) were identified, excluding patients with prior liver transplantation. Baseline PEM was defined by ICD-10 codes for malnutrition, cachexia, or adult failure to thrive within 6 months prior to therapy initiation. Deaths and outcomes within the first 30 days after VEGF initiation were excluded to minimize bias from acute illness at treatment start. Baseline race and ethnicity differences were addressed through propensity score matching. Propensity score matching (1:1) was used to balance demographics, liver disease severity (including cirrhosis, ascites, portal hypertension, and varices), comorbidities, metastatic burden, and prior liver-directed therapies. Outcomes from days 30–90 included overall survival (OS), hospitalization, ICU admission, and gastrointestinal (GI) bleeding. Results: After propensity score matching, 957 patients with baseline PEM were compared with 957 patients without PEM, with well-balanced baseline characteristics. Between days 30 and 90 after VEGF initiation, patients with PEM had worse overall survival (80.6% vs 86.0%; hazard ratio [HR] 1.44, 95% CI 1.13–1.84; p = 0.003). PEM was also associated with higher hospitalization rates (14.3% vs 9.9%; risk ratio [RR] 1.44; p = 0.003). ICU admission rates were similar (4.0% vs 3.6%; p = 0.63), and GI bleeding did not differ between groups (7.1% vs 7.1%; RR 1.00, 95% CI 0.72–1.38). Conclusions: After excluding early deaths and events within the first 30 days of treatment, baseline protein–energy malnutrition remained associated with worse short-term survival and increased hospitalization among patients with HCC treated with VEGF-based systemic therapy. These findings suggest that PEM is not solely a marker of acute illness at treatment initiation but reflects persistent vulnerability during early therapy. Routine nutritional assessment and early supportive interventions may improve outcomes in this population.