Hepatitis C research: Fighting the 'Silent Epidemic'

A study released last week reported that Hepatitis C, the 'silent epidemic,' now kills more people in the US every year (15,000) than HIV (13,000). Approximately 3.2 million Americans are currently infected with the Hepatitis C virus, and most have no idea. Infection is most prevalent among those people born between 1945 and 1965 -- the baby boomers. With numbers like this, Hep C cannot be ignored, and scientists are working earnestly to develop treatments and vaccines for this deadly virus.

Hepatitis C is an infectious disease that primarily affects the liver. While infection is often asymptomatic, chronic infection may lead to scarring of the liver, and ultimately to cirrhosis, which in turn results in liver failure, liver cancer or life threatening esophageal and gastric varices (extremely dilated sub-mucosal veins, prompting bleeding). Hepatitis C is transmitted through blood-to-blood contact associated with intravenous drug use, poorly sterilized medical equipment and transfusions. The virus persists in the liver of about 85 percent of those infected. While persistent infection can be treated with medication, only 50-80 percent of people treated are cured, and the medications carry significant side effects. Those who develop cirrhosis or liver cancer may require a liver transplant, but the virus usually recurs after the transplantation.

Unlike Hepatitis A and B, no vaccine is currently available for Hepatitis C. Researchers at the University of Alberta have made significant progress, however, with a vaccine developed from a single strain that has shown experimental efficacy against all know strains of the virus. The vaccine has taken over ten years to develop, and is another five to seven years away from receiving FDA approval. The challenge in developing a Hep C vaccine, among other things, lies in its high virulence. With even more strains worldwide than HIV, scientists have historically believed that coming up with a vaccine to neutralize all of the strains is impossible. Yet, this vaccine, developed and tested on humans, is capable of eliciting broad cross-neutralizing antibodies against all the different major strains. While the vaccine may make some difference in those infected, it is primarily intended as a preventative measure against acquiring the disease.

Until the experimental vaccine becomes publicly available, those infected with Hepatitis C must rely on therapies, many of which are expensive and carry serious side effects. A research team in California developed a computer model accounting for different treatments, outcomes, disease stages and genetics to measure the cost-effectiveness of undergoing these treatments. With treatments costing upwards of $60,000, and eliciting flu-like symptoms, depression, rectal bleeding, full-body rash and hair loss during the up to forty-eight week treatment cycle, it is important to be confident in the results. Researchers relied on a recently identified DNA sequence in the gene that codes for an immune response regulator to predict whether treatment will successfully clear the virus. Based on this data, the team concluded that triple-therapies, which employ protease inhibitors, an interferon, and an antiviral, are worth the cost, both physical and financial, in those chronic Hepatitis C patients with advanced liver disease.

While these currently available medications target viral proteins to treat Hepatitis C, researchers at UCLA have identified a cell-permeable peptide that may be useful in developing drugs that target cellular proteins. The peptide identified enters the cell and blocks the cascade of cellular events that allows the Hepatitis C virus to replicate, thereby preventing the resulting cirrhosis and cancer associated with the virus. This small peptide binds to heat shock protein (HSP) 70, which is important for viral replication, blocking the interaction between the proteins that are necessary for the replication. Blocking the HSP70 protein rather than the viral protein reduces the chance that patients will develop resistance to the peptide, because there is no direct pressure on the virus that would prompt it to mutate. With ten to twenty percent of patients becoming resistant to currently available drugs, this is an important improvement. The long-term goal with this peptide is to achieve a sustained response -- essentially a cure -- meaning there is no more virus replication.

Each of these developments presents an exciting step in the fight against Hepatitis C. Just as important, though, is continued education for preventing the spread of the virus in the first place. By observing safe practices for needle use and transfusions, many of these deaths may be avoided.