The metabolic liver disease NAFLD (non-alcoholic fatty liver disease): an underestimated health problem

LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH). (NASH), the inflammatory form of NAFLD can follow NAFLD if it goes undetected. LiSyM scientists also investigate liver disease caused by exposure to selected harmful chemicals, drugs and other toxins.

What is NAFLD?

Experts speak of the metabolic liver disease NAFLD when more than five percent of hepatocytes, liver cells in which important metabolic processes take place, have stored fat, and when alcohol consumption has not played a role. Estimates suggest between 20 and 30 percent of the population in Europe suffers from NAFLD. The causes are primarily an unfavorable genetic predisposition and an unhealthy lifestyle characterized by a poor diet and lack of exercise. Weight loss can correct NAFLD in early stages. Failing that, it progresses slowly until the non-inflammatory form (simple or bland fatty liver) develops into the inflammatory non-alcoholic steatohepatitis, or NASH form. Statistically this occurs in up to 20% of those with NAFLD. At this stage, the function of the hepatocytes is already partially disturbed. Between 10-20% of those patients suffering from NASH develop more severe fibrosis, some a pronounced cirrhosis. In some cases, liver cancer develops.

LiSyM wants to improve diagnosis and treatment for patients

The incidence of NAFLD is increasing significantly and represents an underestimated health problem. This is particularly so in industrialized countries where people suffering from common conditions such as obesity, diabetes and high blood pressure are prone to developing NAFLD.

LiSyM researchers focus on ways to improve the diagnosis and treatment of NAFLD in these patients. They want to ensure that fewer people with the lifestyle disorders mentioned above contract liver disease, and otherwise prevent it from worsening in patients who already have it.

LiSyM researchers study NAFLD, and in particular NASH, to identify how and why NAFLD develops, and how NAFLD progresses to NASH. With this knowledge, doctors will be able to prevent its development or diagnose the disease earlier and prescribe effective therapies.

Many liver patients visit the doctor late

Therapies are most effective during the early stages of NAFLD. Unfortunately, patients with liver disease often visit the doctor quite late. Those in the early stage of the disease do not feel any symptoms or pain, and results of blood tests often reveal no signs for a long time. Furthermore, early on, the liver can compensate for the functional changes arising from liver damage; another reason why early damage goes unnoticed.

Yet, at some point, patients tire easily and recognize they have a health problem. Blood test results indicate slightly higher liver enzyme levels, which become higher still over time. Although, at this point, doctors can detect NAFLD easily, treatments are significantly less effective. Whereas the liver can completely recover from the disease if it is diagnosed in the early stages, doctors cannot reverse advanced liver damage. In the worst case, NAFLD can ultimately lead to liver failure, liver cancer and death. In selected patients liver transplantation can be performed but organs are scarce.

How does lifestyle cause liver disorders?

People should be able to protect themselves better from liver diseases like NAFLD. To do so, we need to identify what causes it in a particular patient. Therefore, LiSyM researchers examine the impact of being overweight, of physical inactivity due to a sedentary life style, an imbalanced nutrition, diabetes mellitus type 2 and other risk factors.

As the disease can impair the breakdown of drugs in the liver, standard doses of certain medication can become harmful in patients with liver disease adding new injury to an already damaged organ. For some patients this tips the scale from a stage called ‘compensated’ liver disease to ‘decompensated’ liver disease, a disease stage with high mortality.

LiSyM aims to understand the liver at all levels

For these goals, LiSyM needs to gain as much knowledge as possible about the liver – about its structure, function, disorders and interactions with other organs. Only a sound understanding of the underlying processes will lead to effective new concepts for prevention, diagnosis and therapy. That is why the holistic approach of systems biology offers the best and most comprehensive strategy. In particular the use of disease models, based on existing and new data, shows promise in obtaining novel insights and facilitates drug development without the lengthy animal experimentation of more traditional strategies. These new models reconstruct disease processes and underpin experimental results or uncover relationships and gaps in knowledge. Before they can be applied in single patients, the quality of these simulations is verified with experiments in the laboratory or in clinical studies.