MHH research team investigates the consequences of HEV infection for patients with pre-existing liver damage.
Tested blood samples from patients with liver cirrhosis for hepatitis E viruses and virus-specific antibodies: Dr. Katja Dinkelborg, PhD (right), and Birgit Bremer, medical technologist for laboratory analysis. Copyright: Karin Kaiser/MHH
Infections with the hepatitis E virus (HEV) are very common in Europe, with more than two million cases annually. In Germany alone, up to 400,000 people become infected with genetically slightly different HEV strains during this period, often through the consumption of contaminated pork. There are no specific drugs to treat the virus. In most cases, the infections go unnoticed because they cause no symptoms, and the liver inflammation heals without any lasting effects. However, it can be dangerous for people with a weakened immune system or pre-existing liver damage. A research team from the Clinical Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology at Hannover Medical School (MHH) has now conducted a study to investigate how an HEV infection affects patients with liver cirrhosis—that is, with scarred liver tissue. The result: About half of the patients developed what is known as acute-on-chronic liver failure (ACLF), a severe and life-threatening complication. In half of these cases, the outcome was either fatal or the patients required a liver transplant. The findings have been published in the journal “Liver International.”
HEV infection is underdiagnosed
HEV infections are the most common cause of acute viral hepatitis worldwide. “Nevertheless, even in Clinical Departments of tertiary care hospitals, they are frequently underdiagnosed and go unnoticed,” says Dr. Katja Dinkelborg, PhD, first author of the study. The reason: HEV infections are often simply not considered, and diagnostic tools are not readily available everywhere. However, as a secondary infection, they can place a heavy burden on the liver. For patients with advanced liver cirrhosis, such an infection can have particularly serious consequences. In their study, the researchers examined, among other things, 249 blood samples from patients who were hospitalized at the MHH. They analyzed how HEV influences the course of the disease. In addition to ACLF, the researchers also identified cases of acute liver decompensation, a rapidly developing complication of liver cirrhosis. At this stage, the scarred liver can no longer maintain its functions. This failure can lead to fluid accumulation in the abdominal cavity, the development of varices in the esophagus, or the entry of toxic metabolic byproducts into the brain, resulting in impaired consciousness and confusion. The most severe form of decompensation leads to acute liver failure.
“Our observations suggest that HEV can trigger clinical deterioration in patients with liver cirrhosis,” notes Dr. Dinkelborg, PhD. “At MHH, we therefore monitor HEV closely and test blood for viral RNA when an infection is suspected.” However, even a negative test result does not necessarily mean that an HEV infection is absent. This is because, in some cases, patients do not arrive at the Clinical Department until the viral RNA is no longer detectable in their blood, but the liver damage only becomes apparent at that point. According to the physician, this observation also suggests that HEV is frequently underdiagnosed.
Lack of HEV immune defense
In a subsequent step, the researchers investigated the state of the immune response against the virus in patients with liver cirrhosis. To do this, they tested the patients’ blood serum for a virus-specific antibody. Only one-third of those tested had the appropriate immune response. Two-thirds, on the other hand, had no HEV antibodies in their blood. “These patients with advanced liver cirrhosis remain susceptible to infection,” the physician emphasizes. She therefore hopes to raise greater awareness of the risk of HEV infections among both treating physicians and those affected. This would help prevent life-threatening complications and also facilitate the development of new preventive and therapeutic approaches. Although there is no officially approved treatment for hepatitis E, chronic infections can be successfully treated with the antiviral drug ribavirin.
New treatment approach using neutralizing antibodies
At MHH and TWINCORE, the Centre for Experimental and Clinical Infection Research, researchers are also working on a new treatment approach. In a previous study, they were able to show that neutralizing antibodies from the blood of recovered patients could be helpful. These antibodies could be used preventively and therapeutically to prevent severe courses of life-threatening hepatitis caused by HEV. “The results from our current study show that there is a need for this passive immunization to better protect those affected from HEV infection,” says Dr. Dinkelborg, PhD. However, the neutralizing antibodies must first undergo further development before they can eventually be used in the Clinical Department.
Key term: Hepatitis E
The hepatitis E virus (HEV) belongs to the group of RNA viruses. Normally, HEV has no envelope and, like all non-enveloped viruses, is highly resistant to chemical agents. In Germany and Europe, HEV has its natural reservoir in pigs. The infection can be transmitted from animals to humans; this is referred to as a zoonosis. This often occurs through undercooked or raw meat products, such as ground pork. In tropical regions of the world, infections occur via contaminated water, sometimes leading to major outbreaks.
The original paper, “Acute HEV Infection Is a Relevant Cause of Decompensation and ACLF in Patients With Liver Cirrhosis,” can be found here.
The publication on neutralizing antibodies from the journal *Nature Communications*, titled “Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice,” can be found here.
Text: Kirsten Pötzke