It's well known that people with hepatitis B (HBV) face a higher risk of developing liver cancer.1 Now, doctors at the MD Anderson Cancer Center claim they've found how HBV can help mediate the development of liver cancer in people with the viral infection. For people with hepatitis B, this finding paves the way for a possible treatment, either to prevent liver cancer or for people who already have the disease, the researchers point out.
"This study identified a novel mechanism for how hepatitis B primes liver cells to turn cancerous," explained the study's chief investigator Mien-Chie Hung, PhD, a professor of Molecular and Cellular Oncology at the University of Texas and MD Anderson. "And what we found has potential relevance for other cancers, as well."
Cancer Can Occur in Chronic Infection
Hepatitis B affects an estimated 73,000 people a year in the United States. Of those, 5,000 die each year from illnesses related to the infection, according to the government. In contrast, an estimated 1.25 million people are chronically infected.
HBV is caused by a virus that attacks the liver, and can cause lifelong (chronic) infection, cirrhosis of the liver, liver cancer, liver failure, and death. Symptoms range from jaundice, to fatigue, to abdominal discomfort. But sometimes, people with the disease have no symptoms. HBV infection is spread primarily through sex with an infected person, sex with multiple partners, injecting drugs, living with someone who has chronic HBV infection or contact with infected blood.2
Infection with chronic hepatitis B can lead to liver inflammation, which in turn, may lead to cirrhosis, and eventually, cancer. Hepatocellular carcinoma is the most common form of liver cancer, accounting for 80% of all such cancers.3
"Individuals who carry the hepatitis B virus have a greater than 100-fold increased relative risk of developing hepatocellular carcinoma," explained Hung. "Many researchers have been working to understand how the virus causes this cancer so that potential treatments can be designed."
Hepatitis B Deactivates a Cancer Protector
Hung and his team found that the hepatitis B virus turns off an enzyme known as GSK-3 beta, which normally suppresses tumors and blocks the spread of cancer. Other cancers like those of the breast, colon, kidney and stomach use a similar process that leads to cancer development, the researchers speculated.
Additionally, liver cancer may arise from the activation of a process that involves a protein known as beta catenin. In healthy people, beta catenin sits on the outside surface of cells, helping them stick to other, similar cells in a particular tissue. However, when the protein is found at high levels inside a cell or its nucleus, it works to turn on genes involved in the development of cancer. In this study, up to 70% of all hepatocellular carcinoma tumors had abnormal accumulations of beta catenin within its cells.
The focus of this research was to find out how HBV causes the accumulation and activation of the protein in liver cancer. The research team zeroed in on a gene for the hepatitis B virus known as the hepatitis B 'X' gene (HBX). They found that HBX shuts off the GSK-3 beta enzyme, whose normal role is to "eat away" at beta catenin. As a result, beta catenin invades cells and goes to work promoting cancer. (Another enzyme called Erk also inactivates the GSK-3 beta enzyme, the study found.)
When GSK-3 beta becomes inactive, then beta catenin activity inside cells surges, Hung explained. "This is important because beta catenin [activity] is found in many cancer types," he said.
Blocking HBV's Insidious Work
This study wasn't just about discoveries, however. The team also found a way to rein in beta catenin. They developed a super-active, abnormal form of the gene for GSK-3 beta, and added it to liver cells. The abnormal gene blocked the beta catenin protein in the cells and stopped cancer from building, they reported. "We think it may be possible in the near future to develop novel therapeutic approaches for treatment of the aforementioned cancers, including development of gene therapy and a small molecule that will activate GSK-3 beta," said Hung.
1. Brechot C. Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology 2004 Nov;127(5 Suppl 1):S56-61.
2. Centers for Disease Control and Prevention. Hepatitis B Frequently Asked Questions. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/b/faqb.htm#gen. Accessed August 11, 2005.
3. American Liver Foundation. Liver Cancer. Available at: http://www.liverfoundation.org/db/articles/1093. Accessed August 11, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
