Pressure in the biliary system leads to tissue changes in the liver

The liver produces bile, which is needed in the intestine for digestion. A network of microscopic bile ducts runs through the liver and drains the bile. If the outflow of bile into the intestine is blocked, it accumulates in the liver and can lead to serious liver diseases. Researchers from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, together with experts from the University Hospital Carl-Gustav-Carus (UKD) and Oslo University Hospital in Norway, have discovered that high pressure in the bile ducts alters the structure of liver tissue. They found that increased pressure leads to the disappearance of „apical bulkheads“ - structures that reinforce the ducts. As a result, the bile canaliculi enlarge to form hepatocellular rosettes, which are seen in many liver diseases. This study shows that pressure is a possible common cause of various liver diseases with biliary obstruction and thus contributes to a better understanding of liver diseases.

The research groups led by Prof. Marino Zerial at the MPI-CBG and Prof. Jochen Hampe at the UKD in Dresden in collaboration with the University Hospital in Oslo have found initial indications in their studies that bile stasis in the microscopically small bile ducts can lead to overpressure in the system. In the long term, this overpressure could lead to pathological changes in the liver tissue and thus to liver diseases such as primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC).

A close look into the bile ducts with high-resolution microscopes shows how the microcirculatory system of a liver reacts to pressure: Hepatocytes form transverse connections known as "apical bulkheads", which stabilise the bile ducts. However, if the pressure in the bile ducts becomes too high, these stabilising supports of the hepatocytes begin to give way. This leads to the expansion of the ducts and the formation of new structures, the liver cell rosettes.

For decades, so-called liver rosettes have been used in the diagnosis of cholestatic liver diseases in order to recognise these diseases. These liver cell rosettes - pathologically altered liver cells that are arranged like rose petals around a small opening - can be recognised in tissue samples. However, it was previously unclear why these structures form.

Thanks to state-of-the-art fluorescence microscopy methods, the researchers have now been able to recognise that the liver cell rosettes are cross-sections of the bile ducts in which the overpressure arises due to bile stasis. The scientists have thus solved a riddle about the causes of the formation of these structures, which are considered a recognisable feature of bile stasis in liver tissue. This indicates a direct link between increased pressure in the bile ducts and cholestatic liver diseases and contributes to a better understanding of these diseases.

Carlotta Mayer, first author of the study, explains: "We see liver cell rosettes in the tissue even in the early stages of PSC. This makes them a potential marker structure that can be used for the early diagnosis of PSC and other liver diseases.
The research results suggest that overpressure in the bile ducts may also play a role in other liver diseases, such as hepatitis. This could open up new perspectives for research into these diseases.

„This work is an excellent example of the need for interdisciplinary collaboration between medicine and cell biology. We will now investigate the molecular mechanisms that lead to the formation of these liver rosettes in order to find new perspectives for treatment," emphasises the head of the research group, Prof Marino Zerial.

Article from "idw - Informationsdienst Wissenschaft" from 06/09/2023