The hepatitis E virus (HEV), known to cause severe liver inflammation, is more versatile than previously assumed. A research team from Ruhr University Bochum and the TWINCORE Center for Experimental and Clinical Infection Research in Hanover has shown for the first time that the virus not only infects liver cells, but also kidney cells, where it can multiply. The results, published on June 27, 2025 in the journal Liver International, show that antiviral drugs such as ribavirin are significantly less effective in the kidneys. This could make the treatment of chronic infections considerably more difficult.

Hepatitis E is the main cause of acute viral hepatitis and can be particularly dangerous in immunocompromised patients such as organ transplant patients or pregnant women. Until now, the liver was considered the primary target of the virus. “However, it was known that the viruses can go astray and infect other cells, for example nerve cells,” explains Dr. André Gömer from the Department of Molecular and Medical Virology at Ruhr-Universität Bochum, last author of the study. In cell cultures, the team has now been able to show that HEV also infects kidney cells. “The entire replication cycle of the virus takes place in kidney cells as well as in liver cells,” says Gömer.

An alarming finding: in infected kidney cells, the antiviral drug ribavirin, which is often used successfully in the liver, has a significantly poorer effect. “This is probably due to the metabolic profile of the two organs, which differs significantly,” explains Gömer. This reduced effect could have serious consequences. “It could be that the kidney functions as a reservoir in chronic infections, from where the viruses spread again after a supposedly successful treatment,” says Nele Meyer, PhD student in the Translational Virology research group at TWINCORE and co-first author of the study. Such a reservoir could even enable the virus to adapt to the treatment and develop resistance.

In addition, the team carried out a genetic analysis of HEV in chronically infected patients by comparing viruses from blood plasma, stool and urine. While the stool mainly contains viruses from the liver, those found in the urine originate from the kidneys. “The viruses found in the different samples differ significantly from each other,” reports Dr. Patrick Behrendt, head of the Translational Virology group at TWINCORE and also last author. “This is an indication that the populations have been developing independently of each other for some time and have undergone a kind of evolution in the respective organ.”

The findings suggest that HEV behaves more complexly in the body than previously thought. The kidney as a viral retreat could explain why chronic infections are so difficult to fight. For the future, the researchers see the need to develop new therapeutic strategies that also effectively tackle the infection in kidney cells. The study, supported by the German Research Foundation and the Federal Ministry of Education and Research, among others, provides an important basis for this and shows how urgently further research is needed to meet the challenges posed by hepatitis E.

Original Paper:

Extrahepatic Replication and Genomic Signatures of the Hepatitis E Virus in the Kidney – Wahid – 2025 – Liver International – Wiley Online Library

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