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The hepatitis E virus infects some 70 million people every year. “This infection is the most common form of acute hepatitis and a major global health problem,” says Achim Weber, professor of pathology at the University of Zurich (UZH) and the University Hospital Zurich. In the majority of cases, the infection is asymptomatic or mild. However, sometimes it not only involves serious damage to the liver, but also to the kidneys.
“We’ve known this for a long time, but no one understood exactly why,” says Weber. Now, the two renal pathology specialists Birgit Helmchen and Ariana Gaspert, and molecular biologist Anne-Laure Leblond from Weber’s team – in collaboration with researchers from France and colleagues from various hospitals in Switzerland – have gained an insight into the underlying disease mechanism based on tissue samples from patients.
The infected liver cells produce an excess of a viral protein that can bind with other viral proteins to form a viral envelope. Because the virus’s genetic material replicates to a far lesser extent, the vast majority of the envelopes remain empty when they are secreted by the liver cells. This is how they enter the bloodstream, where they are detected by the immune system, which then forms antibodies that stick to the viral proteins.
These viral envelope-antibody complexes are then deposited in the filter structures of the kidneys, known as the glomeruli. If the complexes accumulate more quickly than they are removed, they can damage the glomeruli, triggering what is known as glomerulonephritis – a pattern of damage that in the worst case can lead to kidney failure.
Weber’s team of researchers discovered this mechanism when they were examining the cause of death of a patient who had received a new kidney years earlier. “From the patient’s medical record, it was clear that his chronic hepatitis E had not been diagnosed straight away,” says Weber. This is not uncommon, explains Weber, as the disease still receives too little attention here in Europe.
“When I was a medical student, we were taught that hepatitis E only affects people in Asia, Africa and Central America,” says Weber. There is now a gradual realization that people in Europe can also contract the hepatitis E virus, particularly if they have a weakened immune system – and that the infection can therefore take hold and become chronic.
“We hope that our discovery will help to raise awareness of hepatitis E, including here in Switzerland,” says Weber. The recently-published findings are also significant in everyday diagnostics. Using the methods developed by Weber and his team to detect the hepatitis E proteins, pathologists can now determine whether the virus is involved in glomerulonephritis.
“This will benefit those affected,” says Weber. This is because if the disease is indeed caused by the hepatitis E virus, medical teams can take countermeasures in time, for example by administering substances to stop the virus replicating, and therefore prevent impending kidney failure.
Anne-Laure Leblond, Birgit Helmchen et al. HEV ORF2 protein-antibody complex deposits are associated with glomerulonephritis in hepatitis E with reduced immune status. Nature Communications. 14 October 2024. DOI: https://doi.org/10.1038/s41467-024-53072-0
