The hepatitis B virus may be involved in the occurrence of liver cancer even at very low concentrations.

© Institut Pasteur/Charles Dauguet - Colorisation Jean-Marc Panaud

Liver cancer: the Peruvian exception


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Updated 11.07.2019

Scientists and physicians are attempting to decipher the ins and outs of the atypical epidemiology of liver cancer in Peru, where young people are particularly affected by the disease. Their research highlights risk factors which were hitherto unknown.

Why do young Peruvians develop liver cancer? The very unusual forms of the disease have been central to the work of scientists and caregivers. The issue is nothing less than the prevention, detection and treatment of this scourge, which is nearly always fatal for patients. “With our Peruvian partners from the Instituto Nacional de Enfermedades Neoplásicas, we have already ruled out several risk factors, such as aflatoxin?Mycotoxins produced by certain fungi proliferating especially on seeds kept in hot and humid atmospherepoisoning, the use of harmful medicinal plants and infection caused by certain liver parasites, states molecular biologist Stéphane Bertani. We have just pinpointed cellular damage which suggests the action of a product toxic to the genome (genotoxic) (1), as well as the underestimated importance of occult hepatitis B infection ?Undetectable infection with current screening tools (2).

Primary liver cancer - hepatocellular carcinoma - is the third leading cause of cancer-related death worldwide. It frequently occurs subsequent to chronic liver diseases which have already significantly altered the liver tissue, such as steatosis?Overload of fat in liver tissue, fibrosis or cirrhosis. Therefore the typical patient profile generally corresponds with that of men over 45 years of age. Nothing of the sort in Peru, where most patients are young adults, teenagers, sometimes even children, of both genders and without known history of liver disorder. They develop tumours which can grow very large before they are detected. To confirm this atypical clinical picture, scientists carried out a comparative histological analysis of non-tumoural liver tissue from Peruvian patients suffering from a hepatocellular carcinoma and healthy patients ?Tissues removed during a tumor resection in the context of hepatocellular carcinoma, for the first, and removal of nodules or liver metastases for the latter..

Cellular damage

We showed that the rates of steatosis, fibrosis and cirrhosis in our patients were very low, similar to those of the control group, says the expert. This confirms that this type of cancer does not fall within a co-morbidity associated with the usual chronic liver diseases. More importantly, we discovered altered cell foci in 61% of liver cancer patients”. Found in large numbers in the liver tissue, these anomalies could be a precursor environment likely to form tumours (tumorigenic). Very similar alterations have already been described in the liver of rats subjected to toxic chemical compounds. “This may suggest that Peruvian patients have been exposed to an environmental agent genotoxic to the liver tissue, believes Stéphane Bertani. As such, we must assess the possible role of mycotoxins derived from Fusarium, a fungus often found in Andean foodstuffs such as quinoa, kiwicha and kaniwa. We should also look into possible agrochemical poisoning”. Nevertheless, scientists do not rule out other risk factors. This is why they are looking into the most common one: hepatitis B infection.

Furtive viral hepatitis

Cluster of altered liver cells (clear cells) in a section of non-tumor liver of a Peruvian cancer patient.

© Luis Cano Ayestas

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Unsurprisingly, serologic tests showed that 51% of Peruvian patients suffering from hepatocellular carcinoma are infected with the hepatitis B virus (HBV). However, their viral load remains moderate, in no way commensurate with the rates found in other parts of the world which require antiviral therapy for the prevention of hepatocellular carcinoma. “More importantly, we discovered very small amounts of viral DNA in 30% of patients who were deemed HBV seronegative, says Pascal Pineau, geneticist with the Pasteur Institute. These furtive infections are undetectable with common screening methods”. In total, the DNA of the virus is found in the body of more than 80% of Peruvian patients. In this country where the incidence of hepatitis B is relatively low, this suggests that the virus is instrumental in the onset of this form of cancer.
The screening and management of hepatitis, notably these insidious infections of which hepatocellular carcinoma may be a clinical expression, pose a challenge, believes pharmacist Eric Deharo. This is why we have launched the Coclican European project, to highlight predictive biomarkers for the risk of liver infection developing into cancer”.

Notes :

1. Cano L., Pablo Cerapio J., Ruiz E., Marchio A., Turlin B., Casavilca S., Taxa L., Marti G., Deharo E., Pineau P. & Bertani S., Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America , Scientific Reports , 30 juillet 2018.

2. Marchio A., Pablo Cerapio J., Ruiz E., Cano L., Casavilca S., Terris B, Deharo E., Dejean A., Bertan S.i & Pineau P., Early-onset liver cancer in South America associates with low hepatitis B virus DNA burden , Scientific Reports , 13 août 2018.

Contacts : Stéphane Bertani / Eric Deharo