Los Angeles, California - A new study led by researchers at the Keck School of Medicine of USC found that drinking alcohol greatly increases the chances that a patient infected by the hepatitis C virus will develop a common type of liver cancer.

The study appeared in the Proceedings of the National Academy of Sciences.

The research clarifies the complex molecular events that link alcoholism and the virus to increased risk of hepatocellular carcinoma HCC, the fifth most common cancer worldwide, according to Keigo Machida, assistant professor of molecular microbiology and immunology at the Keck School of Medicine.

There is ample evidence that chronic liver damage caused by viral infection, alcohol, metabolic syndrome or these factors in combination can increase the risk for the virus, Machida said. However, the molecular mechanism for the synergy among alcohol, the virus and liver cancer has remained unclear.

“Understanding the molecular link holds great potential for future treatment of this particular form of liver cancer,” Machida said. “The signaling mechanism gives researchers a new drug therapy target for treating HCC.”

Machida and his colleagues focused their research on a viral protein, NS5A, which in earlier experiments stimulated high expression of a receptor for bacterial endotoxins, known as Toll-like receptor 4 (TLR4). Alcohol intake increases the risk of leaking bacterial toxin from the gut, which the researchers believe causes over-activation of endotoxin receptor signaling if patients are also infected by hepatitis C virus.

This excess antibacterial reaction then results in an increased risk of tumor growth should the body’s natural anti-tumor response weaken as a result of the infection, Machida explained.

Researchers conducted a series of experiments with mice and also examined liver biopsy samples from human patients infected with the virus and found high levels of the protein NS5A and TLR4. In the subset of patients who were also alcoholics, the researchers saw signs of increased antibacterial response. The research also identified a specific molecule called Nanog, which acts as a stem cell marker in tumor development when activated by TLR4.

“There were several major findings that resulted from this study,” Machida said. “We established a mouse model which will enable us to better understand alcohol and hepatitis C virus infection, and we found the signaling that causes tumor development in mice through the receptor TLR4.”

“More research is needed, but if we are able to target and suppress these molecules identified in the study, we may be able to stop the cancer’s lifeline.”