IMMUNE CELLS IN LIVER DRIVE FATTY LIVER DISEASE, LIVER CANCER
Fatty liver disease --
alongside fatty liver due to massive alcohol consumption -- is mainly caused by
excessive consumption of fat and sugar combined with a lack of exercise or a
sedentary life style. This is referred to as non-alcoholic fatty liver disease
(NAFLD). If NAFLD becomes chronic -- e.g. through the constant uptake of high
lipids and high sugar combined with lack of excercise a chronic inflammatory
response is triggered in the liver tissue in addition. This can lead to
non-alcoholic steatohepatitis (NASH) -- a liver disease with clear detectable
pathologic alteratons of the tissue.
These liver diseases
(NAFLD and NASH), along with chronic viral infections, are the most common
causes of liver cancer, or hepatocellular carcinoma (HCC). In the United
States, about 90 million people suffer from NAFLD. In Europe, the figure is
more than 40 million, and even in threshold countries like India and China, the
number of people affected is rising due to increasingly unhealthy lifestyles.
More worrying, in all of the above mentioned states the numbers of NAFLD and
NASH patients is constantly increasing. Consequently, the incidence of HCC
resulting from NASH and NAFLD is also rising worldwide. In the United States,
HCC is the fastest-growing form of cancer at the moment. No efficient causal
therapy exists for HCC patients of which approximately 800,000 die every year.
T cells involved in
the development of fatty liver disease, NASH and HCC
The mechanisms that
cause diseases such as fatty liver disease, steatohepatitis and HCC are still
not widely understood. However, immune cells, particularly CD8+ T cells and NK
T cells seem to play an important role. This finding was made by a team of
scientists led by Prof. Mathias Heikenwälder, Prof. Matthias Tschöp, Dr.
Kerstin Stemmer, Dr. Kristian Unger, Prof. Ulrike Protzer and the working group
of Dr. Hans Zischka from the Helmholtz Zentrum München together with a team
headed by Prof. Percy Knolle of the Technische Universität München (TUM), Prof.
Achim Weber from Zurich University Hospital and Dr. Monika Wolf, Institute of
Surgical Pathology, University Hospital Zurich. The animal model which was used
to examine the long-term effects of metabolic syndrome* enabled the scientists
to elucidate new mechanisms that cause fatty liver disease and also show how it
can develop into liver cancer.
Inflammatory events
offer starting point for prevention and treatment
The scientists assume
that an existing metabolic imbalance results in the activation and migration of
immune cells to the liver. There, the immune cells interact with liver cells
and trigger an inflammatory response that damages the liver tissue and also
destabilizes the metabolic activity of the liver cells. "Initially it
immune cells promote fatty liver degeneration. The inflammation, which is
triggered by specific immune cells, encourages the progression of fatty liver
pathology and causes NASH to develop. These processes are the basis for liver
cell degeneration, which can cause HCC," explains Prof. Heikenwälder, who
led the study. "Our results provide completely new insights into the
development of these serious liver diseases. Building on this knowledge, we now
want to develop new, preventive and therapeutic strategies to combat these
diseases." The initial studies are already under way in the preclinical
model.
*Metabolic syndrome: a
combination of obesity / abdominal adiposity, insulin resistance, raise levels
of lipids in the blood and raised blood pressure.
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