Liver disease can progress to cancer if unche

image: Lifestyle diseases like obesity are closely linked to non-alcoholic fatty liver disease.
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Credit: Photo credits: “Obesity Health Risk” by Mike Licht, is licensed under CC BY 2.0

Although non-alcoholic fatty liver disease (NAFLD) affects many people worldwide, only a small proportion of patients progress beyond the initial stages of the disease to more serious conditions, the onset of stage-stage liver disease terminal affecting less than 13% of NAFLD. the patients. Disease progression begins with the transformation of NAFLD into non-alcoholic steatohepatitis (NASH), which in turn progresses to fibrosis and eventually cirrhosis. Following this pathway, after cirrhosis, patients develop hepatocellular carcinoma (HCC) and end-stage liver disease.

A New Chinese medical journal to study fills this gap by exploring the risks, potential markers, and strategies for monitoring and treating NASH-related HCC. Dr. Ming-Hua Zheng, lead researcher of the study, says: “The absence of disturbing symptoms makes the early development of the disease relatively imperceptible. And in the absence of any interference from the patient, it becomes easier for simple steatosis to progress to NASH and eventually to HCC.

So, what are the aspects that facilitate this progression? Several metabolic disturbances are thought to play a vital role in the development of NAFLD.

Insulin resistance, whereby your body does not respond to insulin, the hormone that manages blood sugar levels, leads to the generation of excess free fatty acids (FFAs) which interfere with normal functioning of mitochondria in hepatocytes, the main functional cells of the liver that play a key role in the progression of NAFLD to HCC. This means that monitoring diabetes and insulin resistance is crucial in predicting cirrhosis and HCC.

GLA-induced changes can also trigger a condition called lipotoxicity, where high levels of free fatty acids interfere with the glucose metabolism pathway. Lipotoxicity can increase the production of toxic by-products and the likelihood of tumor formation in the liver. A better understanding of the effects of lipotoxicity on NASH would provide additional options for the treatment of the disease and prevent its progression to HCC.

Oxidative stress, a phenomenon where there is an increase in the production of free radicals like reactive oxygen species (ROS), which damage tissues and cellular components due to unregulated oxidation, is another factor responsible for the progression of NASH. Excessive FFAs present in patients lead to overproduction of ROS, which can lead to mutations in mitochondria, increasing the risk of NASH-related HCC.

In addition, hereditary or acquired genetic characteristics of DNA repair enzymes, which differ between individuals, may also be a factor in variation in HCC susceptibility and worsening of NAFLD.

Aging and menopause have an impact on the development and severity of the disease. Thyroid hormone levels can also influence NAFLD. Levels of these hormones can be measured to determine disease progression.

Another important risk factor that critically affects the progression of NASH is an unhealthy lifestyle. Consuming processed foods, an unbalanced diet high in fat, and lack of regular exercise can all contribute to the development of NAFLD.

How to manage this disease then?

Until now, there have been important guidelines for the management of NAFLD/NASH-related HCC. The HCC treatment strategy traditionally follows the format of other diseases like the Barcelona Clinic Liver Cancer. However, the management of HCC has made great progress by improving its methods of diagnosis and screening. This would establish methods to treat the tumor in its early stages, thereby increasing the survivability of the patient.

This study paves the way for future studies to better understand the development of NASH-related HCC and its exact causes. It also highlights the need for early diagnosis of the disease in order to introduce the necessary interventions to prevent its progression. “The continued increase in the prevalence of patients with NAFLD worldwide justifies the need to coordinate appropriate healthcare measures and update existing guidelines for the disease,” said Dr. Zheng.




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