The tumor triggers systemic inflammation, leading to the recruitment and infiltration of innate immune cells into the liver

Following a cascade of molecular signaling in hepatocytes, there is almost a complete loss of the  transcription factor HNF4-α

The loss of HNF4-α disrupts key liver metabolic pathways, including the urea cycle, albumin production, and fatty acid synthesis, leading to cachexia

Increased plasma availability of nitrogen-rich metabolites (ammonia, glutamate, and aspartate) is consumed by the tumor, promoting its progression

Cancer cells survival and tumor progression

Elevated ammonia levels inhibit lymphocyte proliferation and activation, thereby further impairing the immune response against the tumor