Difficult to investigate
It was known that a chronic infection with the hepatitis B virus can lead to liver cancer. But how exactly that happens is largely unclear. That was difficult to investigate. The virus only infects human cells, so a good animal model was lacking. Research with cell lines is the alternative, but it is further removed from the situation in a patient’s body.
Leverorganoid
‘The emergence of liver organoids – developed in the laboratory of Prof. Hans Clevers of the Hubrecht Institute in Utrecht – changed that’, according to Erasmus MC. Liver organoids are a kind of mini-livers, grown in the laboratory from human liver tissue. ‘This gives us the unique opportunity to look patient-specifically at how hepatitis B virus infection progresses and how it can lead to liver cancer,’ explains research leader Dr Tokameh Mahmoudi of Erasmus MC.
scars
In the scientific journal eLife, Mahmoudi and colleagues from Hubrecht Organoid Technology (HUB), the Department of Surgery at Erasmus MC and the Alexander Fleming Biomedical Sciences Research Center in Greece now present the first results of their research. Among other things, they made liver organoids from tissue from hepatitis B patients who had to undergo a liver transplant.
Molecular level
The tissue contained scars called cirrhosis, but no signs of liver cancer were visible to the naked eye. ‘We were therefore surprised that we did find the first signs of liver cancer at a molecular level,’ says Mahmoudi.
Early molecular signature of liver cancer
In more detail, the genes expressed in hepatitis B-infected liver organoids from cirrhotic liver tissue more closely resembled liver cancer than healthy liver tissue. The researchers even found signs of the same early molecular signature of liver cancer in liver organoids made from liver donors who had recovered from hepatitis B.
Third world population infected
Their findings are important in the follow-up of patients with chronic hepatitis B, Mahmoudi said. ‘Hepatitis B and subsequent liver cancer are a major problem worldwide. An estimated one-third of the world’s population is infected with the virus. In only a small proportion the infection becomes chronic, but the diagnosis of liver cancer is often made late. The early signature may serve as a biomarker to detect liver cancer earlier.’
Biobanks
Liver organoids can also help hepatitis B research in other ways, Mahmoudi thinks. ‘The great advantage of organoids is that they are patient-specific living tissue. We can store it in biobanks, grow it, test new drugs on it and study in detail how infection with hepatitis B virus progresses.’
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