New research shows how the hepatitis E virus can lead to kidney disease

The hepatitis E virus affects the liver. But infected liver cells secrete a viral protein that reacts with antibodies in the blood and may form complexes that can damage the filter structure of the kidneys, as researchers at the University of Zurich and the University Hospital of Zurich have demonstrated for the first time.

The hepatitis E virus infects approximately 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 most cases, the infection is asymptomatic or mild. However, sometimes serious damage occurs not only to the liver, but also to the kidneys.

Gain insight into the disease mechanism

We’ve known this for a long time, but no one has fully understood why.”

Achim Weber, Professor, Pathology, University of Zurich

Now the two kidney pathology specialists Birgit Helmchen and Ariana Gaspert as well as the molecular biologist Anne-Laure Leblond from Weber's team – in collaboration with researchers from France and colleagues from various hospitals in Switzerland – have gained insight into the underlying disease mechanism using tissue samples of patients.

The infected liver cells produce an excess of a viral protein that can combine with other viral proteins to form a viral envelope. Because the virus's genetic material replicates at a much lower rate, the majority of the envelopes remain empty when they are secreted by the liver cells. This causes them to enter the bloodstream, where they are recognized by the immune system, which then produces antibodies that attach to the viral proteins.

These virus envelope-antibody complexes are then deposited in the filter structures of the kidneys, the so-called glomeruli. If the complexes accumulate faster than they are removed, they can damage the glomeruli and trigger a condition called glomerulonephritis – a pattern of damage that, in the worst case, can lead to kidney failure.

Hepatitis E often goes undetected

Weber's team of researchers discovered this mechanism while studying the cause of death of a patient who had received a new kidney years earlier. “The patient’s medical records showed that his chronic hepatitis E had not been diagnosed immediately,” says Weber. This is not uncommon, explains Weber, as the disease still receives too little attention in this country.

“When I was a medical student, we were taught that hepatitis E only affected people in Asia, Africa and Central America,” Weber says. It is now gradually being recognized that people in Europe can also become infected with the hepatitis E virus, especially if they have a weakened immune system – and that the infection can therefore become chronic.

Valuable detection methods

“We hope that our discovery will help raise awareness of hepatitis E here in Switzerland,” says Weber. The recently published findings are also important for 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 benefits those affected,” says Weber. Because if the disease is actually caused by the hepatitis E virus, medical teams can take countermeasures in good time, for example by administering substances that stop the virus from multiplying and thus prevent impending kidney failure.