Researchers at the University of São Paulo (USP) in Brazil have discovered a set of genes that can predict how viral hepatitis may progress in the body. They call this network of genes the “neuroimmunoma,” which connects the nervous and immune systems. The neuroimmunoma can serve as a biomarker to predict the severity of liver damage and the risk of liver cancer resulting from a hepatitis virus infection.
The study was supported by FAPESP and published in the Journal of Medical Virology . It analyzed data from over 1,800 samples from public banks in the United States, Italy, China, Spain, France, Germany, the United Kingdom, and Taiwan. The analysis included information on liver tissue and blood cells infected with different hepatitis viruses.
“Our first finding was that defense cells in the blood, or leukocytes, from patients with hepatitis begin to express genes that are typically associated with the nervous system. This shows that instead of operating as two independent systems, they appear to be highly integrated by this network of genes and other molecules that coordinate responses throughout the body, especially during chronic inflammation, such as with hepatitis,” says Otávio Cabral-Marques , a professor at the USP Medical School (FM) and coordinator of the research.
Using machine learning techniques, the researchers found that, as viral hepatitis progresses to liver cancer (hepatocellular carcinoma), the expression of these genes becomes dysregulated.
“As a result, this set of genes may become a biomarker for disease progression. There are clear changes in this deregulation between the early and advanced stages of the tumor, which allows us to monitor the worsening of viral hepatitis,” says Adriel Leal Nóbile , a data scientist and FAPESP scholarship recipient .
Viral hepatitis is a systemic disease that can affect organs besides the liver. According to the World Health Organization (WHO), this neglected disease is the second leading infectious cause of death worldwide, responsible for approximately 1.3 million deaths per year.
Mental health
Analyses showed that specific genes ( NRG1 and DBH ) progressively alter as cancer severity increases. “ DBH is a gene associated with the production of norepinephrine, a neurotransmitter involved in the stress response. This indicates that the stress-related signaling pathway is enhanced in an advanced tumor environment, showing a possible bidirectional relationship between stress and tumor growth,” says Nóbile.
Additionally, neuroimmunoma genes ( NRG1 , OLFM1 , and WDR62 ) are present in both the progression of hepatocellular carcinoma and mental health conditions, such as depression and anxiety.
“Remember Freud’s psychosomatic theory that the body is influenced by the mind? With the neuroimmunoma, we show that it isn’t just the nervous system interfering with the immune system. It’s a highly connected network,” says Cabral-Marques.
The study was based on data from people infected with viral hepatitis, but the researchers believe this neuroimmunoma connection may occur in other diseases as well.
Although the study did not analyze the relationship between hepatitis, the neuroimmune system, and the severity of depression or anxiety, the researchers found evidence of a strong association between the neuroimmunoma and psychiatric manifestations in hepatitis.
“In the future, the neuroimmunoma may serve as a marker both to predict the severity of liver disease and to indicate possible psychiatric complications, which are so common in people with hepatitis. This would make it possible to more definitively prove the relationship between these symptoms and a biological basis rather than an emotional one,” says Nóbile.
About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe .
Journal of Medical Virology
The Neuroimmunome of Hepatitis Patients Associates With Disease Severity
5-Dec-2025