Biotechnology provides new hope against and old enemy: the Hepatitis B virus

Christina Scott

Hepatitis Day is recognised worldwide in July each year. But how many people really understand the devastating impact of chronic hepatitis B virus infection in Africa?

"The hepatitis B virus is endemic to sub-Saharan Africa where it is one of the key environmental risk factors that predisposes chronic carriers to liver cancer and cirrhosis of the liver," says Professor Patrick Arbuthnot of the Department of Molecular Medicine and Haematology at the University of the Witwatersrand in Johannesburg, South Africa. "The link between Hepatitis B and liver cancer is at least as strong as that between smoking and lung cancer."

There are vaccines available. But there are problems with the vaccines. Existing drugs are largely ineffective for people infected with the virus in sub-Saharan Africa. Arbuthnot clarifies, "This is because these drugs are designed to treat patients in whom the virus replicates rapidly. This is not the case in sub-Saharan Africa, where the rate of replication of the virus is slower.

This is mainly to do with the genetic properties of the virus itself. There may be some host factors as well but this is not completely established yet."

Even for patients who have not been infected with the virus, government bureaucracy and costs often prevent them from receiving the existing, life-saving vaccine. The vaccine "is only administered in 5% of babies born in the sub-Sahara," says Arbuthnot, who heads the Hepatitis B Virus Research Programme.

But there are signs of hope, he says: "In South Africa, it has become compulsory for all babies to be vaccinated against the virus since 1995. Other countries with similar legislation in sub-Saharan Africa include Gambia and Botswana. Zimbabwe used to vaccinate but that has stopped." But better use of the existing vaccine does nothing to help the considerable percentage of the population of sub-Saharan Africa already infected with the virus.

It is estimated that 387 million people worldwide are persistently infected with this virus, which amounts to 6% of the world's population. In sub-Saharan Africa, it is thought that the figure is even higher, and that about 10 percent of the population has chronic hepatitis B. From this total of chronic carriers, approximately 25% will develop liver cancer.

It is accepted that the hepatitis B virus alters the gene properties in human liver cells to cause cancer. In South Africa, liver cancer usually develops during early adulthood and has a particularly grave prognosis. "It is rare for tumours to be surgically resectable and most patients die within three months of diagnosis of the malignancy," says Arbuthnot. "There is definitely a need for the development of a new treatment to prevent the serious complications of chronic infection with the virus."

The impact of hepatitis B goes beyond the personal tragedies to generate significant negative impact on economies as people fall ill and are unable to work or farm, or spend their time taking care of sick members of the family instead of more financially rewarding activities.

Using biotechnology, Arbuthnot and his team have already generated therapeutic RNA sequences, or genetically designed treatments, and tested them in liver cell cultures. The three types of RNA sequences that are being used are ribozymes, small interfering RNA and micro RNA. "These are molecular scissors which cut the material of the hepatitis B virus," explains Arbuthnot.

The team has developed the technology that allows these RNA sequences to inactivate hepatitis B virus gene expression specifically. Following these laboratory tests and toxicology assessments, it is planned to test the new treatment in human clinical trials.

"The ultimate goal is to find an effective treatment for hepatitis B for people living in sub-Saharan Africa," clarifies Arbuthnot. In the long-term, he hopes for an effective drug which could be injected.

This is the only study in South Africa focusing on the development of a new treatment for Hepatitis B and certain aspects of the study have already been submitted for patenting. The study was initiated almost four years ago in the Wits University Faculty of Health Sciences. The team will know within about two years whether the therapy will work or not.

"We have had promising and encouraging results," says Professor Arbuthnot. Funding comes from the Innovation Fund of the South African department of science and technology, with a view to job creation in the medical and pharmaceutical fields and reducing dependence on international pharmaceutical companies. But there may also be other spin-offs beneficial to other researchers targeting other viral enemies, such as HIV.

More information:

Prof. Patrick Arbuthnot on (011) 717-2365 or email arbuthnotpb@pathology.wits.ac.za or visit The Hepatitis B Virus Research Programme online. Thanks to Shirona Hassim of Wits University for access to original material.

University of the Witwatersrand www.wits.ac.za

 

July 2004