Obesity paradox role in the immunosuppressive treatment of hepatocellular carcinoma

The “obesity paradox” in hepatocellular carcinoma (HCC) suggests patients with obesity may experience better treatment outcomes compared to patients without obesity. Wang et al highlighted this paradox in HCC immunotherapy, demonstrating superior progression-free survival and overall survival in patients with overweight and obesity treated with lenvatinib and camrelizumab, focusing on hepatitis B virus-related HCC. Mechanisms such as better nutritional reserves, leptin-mediated immune modulation, and reduced protein breakdown may explain these outcomes. Obesity’s role in anti-programmed cell death protein-1 therapy appears could have a benefit, while its effects on other treatments, such as anti-vascular endothelial growth factor therapy, may reduce efficacy. Further research is needed to explore how obesity influences the effectiveness of other most common immunotherapies like nivolumab, pembrolizumab, and bevacizumab, and whether weight loss as well as weight-loss related sarcopenia impacts these benefits.