Spanish researchers for the first time in the world have discovered dozens of cases of rat hepatitis in humans | Society

Researchers in Cordoba have discovered a mysterious new disease, rat hepatitis E, in dozens of patients in Spain, representing the world’s largest series of cases of the disease, first identified in Hong Kong in 2018. virus Rockhepevirus rat (RHEV), is still surrounded by many questions. It is known that about a third of the rats living in Spanish cities carry the pathogen, but there is no clear idea of ​​how it is transmitted to humans. The actual incidence is also unknown, although initial results indicate that more than a hundred cases are reported annually in Spain.

In the face of all this uncertainty, there are two elements to peace of mind. Firstly, there is no sign that the number of cases will increase in the coming years, but rather that the cause of many hepatitis that is still classified as “of unknown origin” is being determined. Secondly, understanding the real impact of the virus and understanding transmission routes will be the first step towards taking measures that can reduce the number of infections.

“We are faced with a very unknown new disease. We have several lines of open research that provide us with data on its prevalence, its true scope as a public health problem, and how it manifests clinically. But there is a lot of work ahead,” says Antonio Rivero Juarez, a researcher specializing in hepatitis at the Maimonides Institute for Biomedical Research in Cordoba (Imibic) and the Network Center for Biomedical Research on Infectious Diseases (CIBERINFEC).

The bulk of the new findings were presented at the recent congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global), held in Barcelona. The scientific society’s Viral Hepatitis Study Group has awarded a €30,000 grant for the first study, which will be led by Imibic and will involve hospitals and research centers in the UK, Sweden, Italy, Hungary, Romania and Turkey. In addition to Spain – to find out the incidence of this disease in these countries.

This hepatitis is part of a group of viral infections that cause inflammation of the liver. The most important of these were named by the letters A to E. In rats, type E was still considered, although this may change. “Hepatitis E virus (HEV) was thought to have eight different genotypes, and the rat genotype was included in this general group. But when carrying out phylogenetic analysis, it was noticed that the differences are large enough to consider it as yet another different genus within the same family,” explains Federico García, head of the microbiological service of the San Cecilio Hospital (Granada) and president of the Spanish Society. Society of Infectious Diseases and Clinical Microbiology (SEIMC). Currently, to differentiate the two diseases, they are called hepatitis E and rat hepatitis E, respectively.

Hepatitis B, C and D tend to develop into chronic and more severe forms with significant mortality (although there is effective treatment for hepatitis C). On the other hand, experts consider A and E to be softer. They can cause acute symptoms, but they usually resolve on their own and the immune system can overcome them within a few weeks, except in people with weakened immune systems. The mortality rate is also significantly lower. In this sense, “as far as we know, infections caused by Rockhepevirus rat (RHEV) are similar to hepatitis E,” adds Federico García.

The virus was first discovered in Germany in 2010, although it was initially thought that it could not infect humans. That changed in 2018 when researchers in Hong Kong identified the first case of the disease in a liver transplant patient, followed by several more diagnoses, up to 16, in the semi-autonomous Chinese city to date.

“We conducted the first study in Spain in which we examined patients with acute hepatitis of unknown origin and identified the first three cases of rat hepatitis in Seville, Cordoba and Pamplona. One of them suffered from metastatic cancer and died of acute liver failure,” explains Rivero Juarez. These results were published in 2022 in a specialist reference journal. Journal of Hepatology.

The first problem the investigation faced was the lack of adequate diagnostic tests. “These cases were just the tip of the iceberg. We didn’t make diagnoses easier because we didn’t have the appropriate tools to do so, so the first thing we had to do was improve them,” says Antonio Rivero Román, professor of infectious diseases at the University of Cordoba and head of the section. at the Reina Sofia Hospital in the city. He is the father of Rivero Juarez, and both of them led research into the new disease.

Research presented at ESCMID Global increased the number of cases identified in Spain to 40, although this figure continues to rise as research progresses. “The new patients came from different parts of Spain, far from each other, such as Andalusia, Galicia, Navarre and Catalonia. This suggests that the virus is present in a large part of the territory. We found 40 cases by analyzing samples from just over 250 patients with acute unexplained hepatitis from 10 hospitals, indicating a prevalence of 14% in this group. These are immunocompromised patients as well as immunocompetent people,” explains Rivero Juarez.

The dozen hospitals studied serve just under 15% of Spain’s population, and the data corresponds to a period of 18 months, so the first estimate puts the annual number of cases in Spain well above a hundred. Of the 40 cases, two died from acute liver failure and the third from other complications apparently unrelated to infection.

“Another direction we followed was to study the presence of the virus in rats. We analyzed samples from more than a thousand animals from all over Spain, as well as the Canary and Balearic Islands. And we saw that about 30% are carriers of the virus. We know little about the effect it has on them, although it is likely that it also causes hepatitis,” the researcher adds.

With the virus confirmed in a significant proportion of rodents and in a significant number of patients, the big question researchers are now asking is how the pathogen spreads from rats to humans. “We have two hypotheses. We know that animals shed the virus through feces and most likely also through urine, so the first possibility is that food and liquids or surfaces and tools that come into contact with them are thereby contaminated, which are then consumed by the animals. people,” explains Rivero Juarez.

The second possibility is that there is another animal species that acts as an asymptomatic intermediate host. As with hepatitis E, the pig is a prime candidate, and infection can occur (though not proven) by eating products made from parts of the animal that have not been cooked or otherwise processed with sufficient intensity to remove the virus. A study recently published in the journal New infectious diseases investigated the presence of the virus on five Spanish pig farms and found it in 44 animals (11.4%). 93.2% of positive tests occurred on a single farm.

Rivero Roman focuses on other clinical problems that also remain to be solved. “We are studying how these hepatitises present themselves to see if they have any characteristics that make them different from the rest. We also want to determine whether the virus causes other conditions, such as neurological processes and febrile syndromes,” he explains.

All experts interviewed agree that there is no reason to believe that in other countries the presence of the virus and cases of hepatitis in rats are less common. If they have not been diagnosed until now, they note, it is because they have not been examined using accurate diagnostic methods. They remember that the virus was first discovered in rats in Germany, then the first case of the disease in humans was found in Hong Kong, and now it is Spain that has made the most progress in research, so it is very likely that the disease actually has a similar global distribution. as in rodents.

Finding out this in Europe is the goal of a European study that will be funded by ESCMID. Participating hospitals will send samples to Cordoba, where they will be analyzed. The first results are expected by the end of the year. “Our goal is to see if this particular type of hepatitis E virus Rat rockhepevirus (RHEV), present in Europe. There is no data and we don’t know how common it is. Therefore, our goal is to find out what is the prevalence and incidence of this type of infection,” says Gülşen Özkaya Sahin, member of the ESCMID Viral Hepatitis Study Group and senior consultant at the Department of Clinical Microbiology in Lund, Sweden.