The INDIVO research network is looking for ways to diagnose bacterial infections in people with liver cirrhosis more accurately and treat them more effectively.
Damage to the liver increases the risk of bacterial infections. Copyright: Karin Kaiser/MHH/KI-generiert
Liver cirrhosis is the fourth leading cause of death in Europe, and the trend is rising. It involves the destruction of liver tissue, which is replaced by non-functional connective tissue. This transformation causes the liver to harden and scar, preventing it from performing its role as the body's central metabolic and detoxification organ. Infections are a particular problem. People with cirrhosis suffer from a complex immune system disorder known as cirrhosis-associated immune dysfunction (CAID). CAID makes them about seven times more likely to get bacterial infections and die from them. Antibiotics help, but they're getting harder to use because more and more multi-resistant germs are around. For targeted antibiotic treatment, it is important to know which bacterium is specifically responsible for the infection. However, conventional methods for detecting pathogens are time-consuming and often not sensitive enough, which is why broad-spectrum antibiotics are frequently used, further promoting the spread of resistance.
A research team led by Professor Benjamin Maasoumy, Senior Physician at the Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology at Hannover Medical School (MHH), is now using AI-based analysis methods to find new ways to make diagnoses more accurate and treatment more personalised, tailored precisely to the individual patient's risk of infection and the severity of the infection. The INDIVO project is being funded with around three million euros over five years as part of the programme to expand personalised medicine by the Lower Saxony Ministry of Science and Culture and the Volkswagen Foundation.
Intestinal bacteria are the most common source of infection
The exact mechanisms of CAID are not yet fully understood. However, various factors appear to play a key role, such as high blood pressure in the portal vein, which transports oxygen-poor and nutrient-rich blood to the liver. Inflammatory reactions caused by increased infections and an unfavourable change in the intestinal flora also allow bacteria from the gut microbiome to migrate through the intestinal wall into the bloodstream, worsening the course of the disease. ‘Intestinal bacteria are considered the most common source of infection and primarily cause urinary tract infections and peritonitis,’ says Professor Maasoumy, who also conducts research on liver infections in the RESIST Cluster of Excellence. "The latter are particularly problematic, as they can lead to further complications such as confusion and coma and are responsible for up to 30 percent of patients dying within the first month. Timely diagnosis and immediate initiation of appropriate antibiotic treatment are therefore crucial." And the clock is ticking, because with every hour of delay in initiating effective antibiotic treatment, mortality increases by three percent.
Fine-tuning the settings
‘The dilemma is that broad-spectrum antibiotics are often used because we don't have a second chance to control the infection in patients with severe cases,’ says the liver researcher. ‘At the same time, about 80 percent of those affected are overtreated.’ Professor Maasoumy and his team now want to fine-tune the parameters for diagnosis and treatment. They want to identify the immune system of cirrhosis patients and their general state of health on an individual basis, identify the infectious agents and combat them directly. They also want to determine which patients are eligible for prophylactic treatment with fluoroquinolones, for example. This antibiotic has been shown to reduce the risk of peritonitis and can improve overall survival. ‘However, the criteria originally proposed for selecting patients for primary prophylaxis remain controversial and do not appear to be sufficiently targeted,’ notes the hepatologist.
Improving the prognosis for cirrhosis
The researchers now want to determine the gut microbiome of those affected, examine their immune systems, carry out blood tests and analyse and evaluate all the data using AI-based methods. ‘The aim is to get the infections under control so that the liver can rest and recover,’ emphasises Professor Maasoumy. This is because the liver is the only organ in our body that can regenerate and grow back. And this even works when the tissue is permanently damaged. ‘It used to be thought that cirrhosis of the liver was the irreversible final stage of chronic liver disease,’ notes the hepatologist. "Today, we know that effective treatment of the underlying disease significantly improves the prognosis for cirrhosis of the liver.‘ Professor Maasoumy is certain that this approach helps even the most seriously ill patients who need a new organ. ’If we can spare them additional infections and inflammation, we also avoid unwanted complications and, above all, death while on the waiting list for a transplant."
The INDIVO project (Individualised Prevention and Treatment of Infections in Patients with Liver Cirrhosis), led by the Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, is linked to the MHH research focus ‘Infection and Immunity’. It is being carried out in cooperation with the MHH Institute for Medical Microbiology and Hospital Hygiene, the Helmholtz Centre for Infection Research (HZI) in Braunschweig and the Technical University of Braunschweig.
Text: Kirsten Pötzke