Assessing risks in acute decompensated cirrhosis

With the help of the Europe-wide PREDICT study, an international research association determined three forms of acute decompensated liver cirrhosis.

14 European countries are involved in PREDICT

With the help of the Europe-wide PREDICT study, an international research association determined three forms of acute decompensated liver cirrhosis.

If the body can no longer compensate for the gradual failure of the liver as a result of cirrhosis, there is a risk of acute decompensation of cirrhosis. In some patients, this quickly develops into an often fatal acute-on-chronic liver failure, in which other organs, like the kidneys or brain, fail.

An international team of researchers led by Prof. Jonel Trebicka from the Frankfurt University Hospital (in German: Universitätsklinikum Frankfurt) has conducted a study to find out which patients are particularly at risk. The scientists have thus laid the foundation for the development of preventive therapies for acute-to-chronic liver failure.

Compensatory mechanisms of the liver

The liver has many functions: It stores nutrients and vitamins, produces glucose, coagulation factors and hormones, and breaks down toxins, medicines, and alcohol. Chronic heavy alcohol consumption, viruses or other diseases can overload the liver and cause chronic illness. If left untreated, chronic liver disease in its final stage leads to cirrhosis of the liver, in which liver tissue is converted into connective tissue and the liver is less and less able to fulfill its tasks. The consequences: The blood's ability to coagulate is reduced, toxic metabolic by-products accumulate, the liver is no longer properly supplied with blood, and the blood pressure in the hepatic portal vein (HPV) rises.

The body tries to compensate for reduced liver functions. For example, as a result of the increased HPV pressure, bypass-circuits form through veins in the esophagus, stomach, and intestines, which dilate to form varicose veins. If, as the disease progresses, such compensation is no longer possible at some point, acute decompensation of the liver cirrhosis is present, and the situation becomes life-threatening: tissue fluid (ascites) builds up in the abdominal cavity, bacterial infections occur and internal bleeding develops, for example in the esophagus. Mental concentration difficulties, mood swings, or drowsiness are signs of brain poisoning (hepatic encephalopathy), which can lead to a hepatic coma.

The PREDICT study

A Europe-wide clinical study under the direction of Prof. Trebicka, conducted under the umbrella of the European Foundation for the Study of Chronic Liver Failure (EF-Clif), has for the first time determined three clinical variants of patients who were admitted to hospital with acute decompensation of liver cirrhosis.

The first clinical course variant is characterized by high levels of inflammation in the blood, which indicate inflammatory reactions throughout the body. Within three months of hospitalization, several organs of the body fail: acute decompensation becomes "acute-on-chronic liver failure" (ACLF). This is why physicians called this variant Pre-ACLF. More than half of the patients die from it, and after one year only a third of them are alive.

Patients in the second clinical variant do not develop ACLF and have moderate inflammatory values, but suffer from a significantly increased blood pressure in the HPV. About 20% of them die within the following three months and a further 15% within the following year. This variant is referred to as an "unstable decompensated cirrhosis”.

Patients in the third clinical variant do not show any severe inflammation or frequent complications. They do not develop ACLF in the first three months. Within a year, however, one in ten of these patients still dies. This variant is also referred to as a "stable decompensated cirrhosis".

Study leader Prof. Trebicka explained: "We are now working intensively on developing new diagnostic options, especially for the group of pre-ACLF patients, so that this group can be identified before they are admitted to hospital and countermeasures can be initiated at an early stage. The development of preventive therapies for the often fatal ACLF is one of our most important research tasks in this context".

Prof. Dr. Stefan Zeuzem, Dean of the Department of Medicine as well as Director of the Medical Clinic I at the Frankfurt University Hospital and co-author of the study, added: "Liver diseases are one of the main focuses of the Medical Clinic I, and we offer numerous specialist outpatient clinics for patients with acute and chronic liver diseases. On the one hand, this enabled us to observe patients for the study. On the other hand, the research results on improving ACLF prevention and therapies very quickly benefit all patients".