The most effective therapy for non-alcoholic fatty liver disease (NAFLD) is
lifestyle modification and weight reduction. This can be achieved in the long term
in patients with morbid obesity through surgical intervention and thus lead to
significant improvement of fatty liver. Despite the outstanding improvement or
often even complete regression of fatty liver, and amelioration of inflammation
in the liver ("steatohepatitis" or NASH), an increase in liver fibrosis has been
described in up to 19% of patients after obesity surgery. Fibrosis is the most
important predictor of liver disease progression and is associated with increased
morbidity and mortality. The underlying mechanism why some patients have
progression of liver fibrosis despite successful weight loss, is not yet clear.
Increased intestinal permeability, and thus exposure of the body to bacteria and
bacterial components from the intestine, has been causally linked to
inflammation of the liver and progression of NAFLD, and is more common in
patients with morbid obesity. To date, however, there have been no studies
showing the course of intestinal permeability and its effect on the liver after
obesity surgery in particular in tissue samples.
The aim of the funded work is to investigate changes in intestinal permeability
after obesity surgery, as well as differences between patients with and without
an increase in liver fibrosis.
Based on this work, risk factors and predictors of fibrosis progression will be
investigated to identify patients at increased risk before surgery. In addition, new
therapeutic approaches to improve liver fibrosis will be investigated in an animal
model, which might allow the development of tailored treatment concepts for
patients with morbid obesity.