Cure cancer before it starts
Will early hepatitis B antiviral therapy help prevent liver cancer?
Hepatitis B virus, as is known, not only provokes inflammation of the liver in acute or chronic form, but also leads to the development of cirrhosis and cancer of this organ. And recently, scientists have found out that the virus triggers the process of malignant degeneration of liver cells very early – sometimes decades before the oncological diagnosis.
According to WHO, in 2019 there were almost 300 million people in the world with chronic hepatitis caused by the hepatitis B virus, and 820 thousand people died from this disease, mainly as a result of cirrhosis and liver cancer.
Hepatitis B virus infection is the main cause of the development of the most common malignant liver tumor – human hepatocellular carcinoma (primary liver cancer). The reason for the appearance of a cancerous tumor is the integration of viral DNA into the genome of hepatocytes, but this process has not been fully studied.
Recently, an international team of scientists analyzed about 300 samples of hepatocellular carcinoma collected during the international project Pan-Cancer Analysis of Whole Genomes (PCAWG). Using DNA sequencing techniques, they characterized mutations in the genome of human liver cells caused by the hepatitis B virus, comparing them with the genome of "normal" cells from blood samples of the same patients. Article by Alvarez et al. Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture published in the journal Nature Communications.
In the cells of 51 tumor samples, 148 events of the "embedding" of viral DNA into the cellular genome were detected. Moreover, in half of the samples, these were non-standard situations: large-scale interchromosomal rearrangements, including the formation of chromosomes with two centromeres and the loss of end sections of DNA with telomeres playing the role of "protective caps" of chromosomes. It turned out that such non-canonical changes in the cellular genome caused by the insertion of viral DNA lead to disruption of two and a half hundred tumor suppressor genes that prevent the development of cancer. And among these genes, 37 are related to the development of human hepatocellular carcinoma.
At the same time, based on the analysis of characteristic combinations of mutation types resulting from certain mutagenesis processes, it was possible to establish that such events can occur years before the development of the tumor. So, in one of the patients, a mutation associated with the loss of the telomeric portion of the chromosome appeared two decades before the oncological diagnosis.
Of course, the development of hepatocellular cancer is not always associated with infection with hepatitis B virus, and not all patients with chronic hepatitis will develop it. However, the results of this work raise questions about the need to prescribe antiviral therapy to patients already at the stage of immune tolerance, when there is still no immune response to infection, nor pathological changes in biochemistry and liver tissue. Currently, antiviral therapy is not recommended at this stage, but already at this time the active reproduction of the virus, accompanied by the insertion of viral DNA into the genome of hepatocytes, can trigger their malignant degeneration.
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