Liver tumor, watch out for metabolism. Obesity and insulin resistance are a lethal mix

2024-04-12 10:43:00

Liver cancer, watch out for metabolic syndrome. Obesity and insulin resistance are a lethal mix

Those suffering from metabolic syndrome have a greater risk of developing cancer. On the report, the XXX National Congress of Digestive Diseases which sees the large presence of the Italian Society of Gastroenterology and Digestive Endoscopy (SIGE), underway in Rome until tomorrow, dedicates a session to illustrate the evidence acquired so far, the drugs being tested, the endoscopic techniques for weight reduction and the numerous studies on the Mediterranean diet and the microbiome. Among the components of metabolic syndrome, in particular, “obesity increases the availability of insulin-stimulating factors which, in turn, increase inflammation and the risk of incurring neoplasms of the gastro-intestinal tract. As has been demonstrated, patients who combine obesity and insulin resistance are exposed to a high risk of developing liver cancer, but also colon cancer and other tracts of the digestive system“, explains Luca Miele, researcher at the Catholic University of the Sacred Heart of Rome.

Weight loss for patients with metabolic syndrome is confirmed to be the best strategy to lower cancer risk. “New drugs for weight reduction could also be effective in the medium and long term in the prevention of liver cancer,” explains Professor Miele. “Furthermore, bariatric surgery techniques have already been shown to lower the risk of liver cancer, thus confirming their long-term effectiveness in reducing the chances of liver cancer.”

The most frequent tumors of the digestive system, linked to metabolic syndrome, are liver, colorectal and pancreatic cancer. “Less frequent – ​​he comments Filomena MoriscoFull Professor of Gastroenterology at the University of Naples Federico II – are those of the stomach and esophagus, although there is still a correlation. Metabolic syndrome presents a set of various components, such as obesity, dyslipidemia, diabetes and arterial hypertension, and each of them has a different weight, in relation to the different tumors. For example, in the case of colorectal cancer, the most important component is linked to obesity, low HDL cholesterol level and diabetes. In liver cancer, diabetes plays a major role, but also obesity and hepatic steatosis. It is clear that patients, given the correlation, must be periodically monitored. What should emerge, especially in the field of general medicine, is that the risk of colorectal and liver cancer is high in obese and diabetic subjects, linked to the presence of hepatic steatosis and steatohepatitis, and it is advisable, at least for subjects at higher risk maintain a surveillance regime, via an ultrasound”.

NEW DRUGS. Last year the nomenclature Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) replaced the old one Non-alcoholic fatty liver disease (NAFLD), in order to highlight the metabolic root of this liver disease. “With the new nomenclature – he explains Elisabetta Bugianesi, Full professor of Gastroenterology at the University of Turin – the condition in which the patient has a systemic disease is described, with dysmetabolic alterations in various organs and the possibility of experiencing different outcomes, such as the risk of cardiovascular as well as hepatic mortality. The new nomenclature – he adds – highlights the need for a multidisciplinary approach: in fact, it is not only the liver that can be treated, but also the comorbidities present, such as diabetes and dyslipidemia. The first step of therapy is therefore to control the metabolic factors that caused it”.

“As hepatologists – underlines the professor Bugianese – we are working to stop or slow down the progression of fibrosis in MASLD and in particular MASH (Metabolic-dysfunction associated steatohepatitis), which could lead to cirrhosis and increase the risk of hepatocarcinoma. So far – he continues – the pharmacological trials have been carried out on non-cirrhotic patients and, when the drugs are approved, the treatable patients will be those with MASH, characterized by hepatocyte necrosis accompanied by moderate or severe fibrosis”.

Of the most promising drugs being tested, which act on metabolic causes, “there are GLP-1 receptor agonists, in particular semaglutide (in phase III), and dual GLP-1/GIP or GLP-1/GCGR receptor agonists (in phase II)”, recalls the professor from the University of Turin. “They are very powerful drugs – she observes – because they not only reduce weight and reduce histological damage in the liver, but also have a cardio-protective action. However, they have not yet been approved for MASH. The only drug approved so far by the FDA is resmetirom, an agonist of the beta receptor of thyroid hormones on the liver, which has a very powerful action on steatosis as it increases fat oxidation at the organ level and improves activity mitochondrial in liver cells. In phase III, it showed resolution of MASH, but also of fibrosis in 25% of cases”.

Another class of drugs that act on metabolic causes is represented by pioglitazone, recommended in previous guidelines for the treatment of MASH (although not approved for MASH but only for the treatment of type 2 diabetes). Pioglitazone eliminates visceral and hepatic fat, returning it to the subcutaneous adipose tissue. “At the moment – ​​comments the professor – a drug of the same class (pan-PPAR-agonist), lanifibranor, which acts in terms of resolution of MASH and improvement of fibrosis, is being tested in phase III”.

THE RIGHT SYNERGY. Also the scientific evidence of the preventive activity of tumors of the gastrointestinal system by the Mediterranean diet they are multiple. “The traditional Mediterranean diet was described for the first time in a scientific work in 1957”, recalls Ludovico Abenavoli, associate professor of Gastroenterology at the “Magna Grecia” University of Catanzaro. Since then, “a series of important studies have been developed to demonstrate effectiveness in the prevention of chronic non-communicable diseases. Today we know that a diet highly rich in fruit, vegetables and functional foods rich in antioxidants has an effective preventive action on chronic pathologies, including tumors of the digestive system. It is a winning diet due to the synergistic action of all foods.” Some foods have demonstrated excellent properties in studies. For example, the peel of Apple announces contains chlorogenic acid, effective in preventing tumors of the gastrointestinal system. The bergamot contains the bergamottinaa very powerful antioxidant, which reduces the development of tumor cell clones including those of the breast, endometrium and gastrointestinal system. Extra virgin olive oil it has a high concentration of saturated fatty acids (omega 3 and 6) which prevent cardiovascular risk, but it is also rich in antioxidants which act on the digestive system. The Red wine it contains a powerful antioxidant, resveratrol, but “the important thing – recalls Professor Abenavoli – is not to exceed two glasses a day (one per meal) and only if you have no pathologies”. Finally, a curiosity: lo stockfishwhen treated with the spring waters of the southern areas, rich in microelements (magnesium, zinc and potassium), takes on important nutritional properties.

Regarding the action of the Mediterranean diet on microbiotathat is, on the billions of bacteria that populate the intestine (in particular the small intestine), studies reveal that when it is altered and a dysfunction occurs, called dysbiosis, the risk of developing polyposis and colon cancer increases, which has increased more in recent years. “In order not to alter the microbiota – concludes the expert -, it is necessary to follow a Mediterranean diet rich in fruit and vegetables with the integration of probiotics, administered in cycles and never continuously. The bacterial strains that have the greatest scientific validity are in particular the lactobacilli”.