Home Health Liver failure caused by attack on blood vessel cells

Liver failure caused by attack on blood vessel cells

Hepatitis: liver failure attributable to the compromised blood supply.

A disease of the liver with viral hepatitis, for example, the hepatitis B virus can advance in very different ways: the liver inflammation (hepatitis) can heal again with no issues; become chronic and require lifelong medication, or take a fulminant – i.e. possibly deadly – course. In the last case, the immune-intervened harm to the liver is severe to the point that the organ fails, leaving a liver transplant as the final treatment alternative.

Hepatitis infections focus on liver cells or hepatocytes. The immune system attempts to bring the disease under control by assaulting and obliterating the tainted liver cells with the assistance of certain immune cells, known as killer T-cells. It was recently accepted that this procedure was additionally in charge of the serious organ damage that goes with intense hepatitis.

Now, scientists at the Technical University of Munich (TUM) comes with a completely different explanation that- the organ failure is not in fact caused by the death of liver cells, but by defects in the vascular (blood vessel) system.

The liver is home to important cells called liver sinusoidal endothelial cells, or LSECs for short. These connect the cells of the liver to the vascular system and direct the trading of nutrients and oxygen with the blood. They additionally can display little parts of infections on their external membrane, likewise to immune system cells.

The specialists say that the killer T-cells explicitly identified these viral particles, mistaking the LSECs for infected liver cells and annihilating them. To this end, they utilized proteins that incorporate into the cell membrane of the target cell and shape a pore. Known as perforins, these proteins perforate the layer and wreck the cell.

Dr. Dirk Wohlleber, Research Group Leader at TUM said, “We observed that the elimination of LSECs by the immune cells has an enormous impact on the liver tissue. Blood flow within the liver is hugely disrupted, with large numbers of liver cells – even those not infected – dying as a result.”

“This immune response has a much more dramatic effect than the attack on liver cells that are actually infected. This discovery was made possible by a new mouse model specially developed by the researchers to replicate the fulminant course of viral hepatitis.”

Percy Knolle, Professor of Molecular Immunology said, “Only now that we have pinpointed the actual destructive mechanism in acute hepatitis can we consider new treatment strategies and specifically target this process. Using their mouse model, the researchers were able to show that a new active substance can prevent fulminant hepatitis.”

“This is a perforin inhibitor, which stops the killer T-cells from forming pores and thus safeguards the LSECs from attack. This agent successfully protected the mice from developing fulminant hepatitis, since the LSECs remained intact, preserving the blood supply to the liver cells.”

The study is published in the journal Nature Communications.

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