Liver Treatment

Fatty liver disease can only be diagnosed with ultrasound

28.09.2021

Every fourth adult over 40 and every third overweight child in Germany have fatty liver disease. In most cases it is non-alcoholic fatty liver disease, which is mainly caused by obesity, an unhealthy diet and lack of exercise and, if left untreated, can lead to liver inflammation, cirrhosis or cancer. The German Society for Ultrasound in Medicine (DEGUM) emphasizes that a fatty liver can be recognized by ultrasound well before the onset of symptoms. The extent of liver damage can also be determined using a special ultrasound technique, elastography. With contrast-enhanced sonography (CEUS), a reliable liver cancer diagnosis is also possible. Ultrasound is therefore of great importance in the diagnosis and monitoring of liver diseases.

Often those affected do not notice the fat deposits for years. "A symptom like fatigue is rarely associated with the liver," explains DEGUM expert PD Dr. med. Thomas Karlas, head of the interdisciplinary central ultrasound unit at the Leipzig University Hospital. It is therefore all the more important to identify potential risk groups at an early stage.

Fatty liver can have different causes. These include, for example, liver inflammation caused by hepatitis viruses or excessive alcohol consumption. If these reasons can be ruled out, it is often a "non-alcoholic fatty liver disease" (NAFLD). "In most cases, it arises as a result of years of unhealthy diet and a lack of exercise," explains Karlas. Above all, being overweight - especially belly fat -, a permanently elevated blood sugar level, elevated blood lipid levels and high blood pressure are the risk factors. In addition to high-fat foods, high-sugar foods and drinks favor non-alcoholic fatty liver. "Since it is estimated that one in four adults worldwide lives with a fatty liver, an ultrasound examination should be carried out if the risk factors mentioned are present," advises the expert. Also in overweight children, a possible fatty liver must be considered.

If left untreated, fatty liver can lead to liver inflammation. "The liver tissue is increasingly scarred by chronic inflammation, and liver function decreases in advanced stages," says Karlas. In around five to ten percent of NAFLD patients, advanced scarring of the liver tissue, known as fibrosis, occurs in the course of the disease, which can progress to cirrhosis of the liver. "There are currently no specific drug therapy options available for NAFLD. The diagnosis and assessment of the course are therefore aimed in particular at the timely detection of complications," explains the DEGUM expert.

Ultrasound is also useful for showing the extent of liver damage. "So-called elastography is an ultrasound method that is used to determine the stiffness of the liver," explains Karlas. Because the more the liver scars, the stiffer it is and the more advanced the disease is. "If the fibrosis is already advanced, regular ultrasound examinations should be carried out due to the high likelihood of developing liver cancer," advises the expert. If a suspicious lump is detected, a contrast-enhanced ultrasound examination is suitable for correctly identifying liver cancer in up to 90 percent of cases.

"For the diagnosis, assessment and follow-up of the fatty liver disease, ultrasound is very important, also because tissue removal can often be dispensed with", concludes Dr. Karlas. There is an urgent need for doctors to be well trained in the use of modern ultrasound procedures. DEGUM offers numerous advanced training courses for this purpose. Because if the fatty liver is detected early, the organ can often recover completely with the help of a change in diet and lifestyle.

Contacts between cells control liver regeneration

22.09.2021

The molecular mechanisms by which adult liver cells trigger regeneration are still largely unknown. Around 29 million people in Europe suffer from chronic liver disease such as cirrhosis or liver cancer. They are a leading cause of illness and mortality, with liver disease accounting for around two million deaths worldwide each year. There is currently no cure and liver transplants are the only treatment for liver failure. Scientists are therefore exploring new ways of using the liver's ability to regenerate as an alternative to restoring its function.

It has been known since Aristotle that the human liver has the greatest regenerative capacity of all organs in the body and can grow back even after an amputation of 70%. This enables transplants from liver donors. Although the liver regenerates completely after an injury, the mechanisms that regulate how the regeneration process is activated or stopped are still unknown. Researchers at the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, the Gurdon Institute (Cambridge, United Kingdom) and the University of Cambridge, Department of Biochemistry, have now discovered that a regulating cell type - mesenchymal Cells - which can activate or stop liver regeneration. The mesenchymal cells do this via the number of contacts they make with the regenerating cells (epithelial cells). This study suggests that failures in the regeneration process that can lead to cancer or chronic liver disease are caused by an incorrect number of contacts between the two types of cells. The study has been published in the journal "Cell Stem Cell".

Scientists from the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, together with colleagues from the Gurdon Institute at Cambridge University, are researching the biological basis of liver regeneration in adults. In 2013, Meritxell Huch and Hans Clevers developed the first liver organoids - miniature liver tissue that was created from mouse liver cells in a Petri dish in the laboratory. The researchers even succeeded in transplanting the organoid into a mouse, where it could take over liver functions. In 2015, they successfully applied this liver organoid technology to the cultivation of a human liver in a Petri dish based on human liver samples. In 2017, they developed a similar system based on human liver cancer.

The two most important functional cells in the adult liver are the hepatocytes, which perform many functions in the liver, and the ductal cells, which form the network of tiny ducts that carry bile to the intestines. These work together with other supporting cells, such as the blood vessels or the mesenchymal cells. Initially, the research team only used ductal cells from the bile duct to build liver organoids.

To improve on this model and make it more similar to the real liver, PhD student Lucía Cordero-Espinoza and postdoctoral fellow Anna Dowbaj planned to build a more complex liver organoid that better mimicked the cellular interrelationships and architecture of adult liver tissue. To do this, they added liver mesenchyme - a kind of regulatory cell of connective tissue that supports the tubular structure of the bile duct. "We placed the mesenchymal cells in a Petri dish next to the organoid from the ductal cells and saw that they did not touch or connect, as is the case in natural tissue," says Anna Dowbaj.

The researchers turned to Florian Hollfelder from Cambridge University, who knew a method that made it possible to connect cells in tiny gels so that they can meet and make contact. Anna Dowbaj continues: "We were excited to see how our new and more complex organoid replicates the architecture of the tissue in the shell, so we decided to study the behavior of the cells and filmed them under the microscope. To our surprise, we got one completely Observe unexpected behavior: The tissue (organoid) shrank on contact with the mesenchymal cells, but grew when there was no contact. This strange behavior was very startling, but it could help us to clarify why the tissue grew or stopped growing during the regeneration process growth."

In a healthy liver there is a certain number of contacts between the ductal cells and the mesenchymal cells, which signal the ductal cells that they should not multiply and should simply remain as they are. Once the tissue is damaged, the mesenchymal cells reduce the number of contacts they make with the ductal cells so that they can multiply to repair the damage. From their observations, the researchers concluded that it is not the number of the two cell types but the number of cell contacts that determines how many cells are produced to repair the damaged tissue. Too many touches by mesenchymal cells mean fewer or no new ductal cells are formed, while fewer touches mean more cells are formed. This regulation is very important because if there is no signal for the ductal cells to stop multiplying in order to repair tissue, it can overpower and lead to cancer.

Meritxell Huch, who led the study, sums up: "It is the first time that we have been able to make these contacts visible, and we have proven for the first time that they exist. This was possible thanks to our organoid systems. Even if we have carried out our experiments in a Petri dish outside the living body, we assume that the same process takes place in the living organism. We have been able to observe this at certain times during the regeneration process. We have not yet been able to observe this in the living organism because the Technology for this does not exist.While our study focused on the ductal-mesenchymal interaction in the liver, we can imagine that similar mechanisms take place in any other system in which cell numbers change dynamically, such as in the lungs or breast tissue Of course, in the future we would like to produce a liver organoid with all cell types ll. Such an organoid could be used to test drugs and see whether they affect not only the regenerating cells but also their supportive environment. But for that we have to wait until the technology is available."