Disease
Liver cancer is the fourth most common cause of cancer-related death worldwide.
In Belgium, liver cancer is the 8th most frequent cause of cancer-related deaths in females and the 10th in males (Belgian Cancer Registry). Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers and is refractory to almost all currently available anticancer therapies, with a 5-year survival rate of approximately 15%.
The liver is essential for maintaining homeostasis in nearly every system in the body, and its function is compromised in obese patients. Because of its close interaction with the gastrointestinal and endocrine systems, the liver participates in the digestion, metabolization, and storage of nutrients. The functional hepatic unit, or lobule, is composed of hepatocytes, which are parenchymal cells that constitute between 70-80% of the liver mass. The remainder of the liver contains nonparenchymal cells, including Kupffer cells, sinusoidal endothelial cells, stellate cells, and cholangiocytes. These highly specialised cells coordinate several functions such as metabolism, drug detoxification, cholesterol homeostasis, blood protein synthesis, bilirubin metabolism, urea cycle, immunity, and other functions. Hepatocytes perform a dynamic range of reactions in response to nutrient availability and hormones, adjusting their rates according to the metabolic status of the organism.
Obesity is a major cause of metabolic dysfunction-associated steatotic liver disease (MASLD), which comprises steatosis, an excessive accumulation of lipid droplets, mostly triglycerides, in hepatocytes. This can progress to inflammation and cell damage, generating metabolic dysfunction-associated steatohepatitis (MASH). Patients with MASH are substantially more likely to develop liver failure, clinically severe cirrhosis, and eventually hepatocellular carcinoma (HCC).
Despite the high prevalence of both HCC and MASH, the different mechanisms of malignant hepatic cell reprograming in obesity remain unclear. This precludes the early identification of obese patients with a risk of developing HCC and consequently reduces overall survival.