Mysterious Hep A Immune Response Has Implications For Hep C Research

Hepatitis C virus

SRxA’s Word on Health was interested to read a new animal study which sheds new light on the nature of the body’s immune response to hepatitis C virus (HCV) and hepatitis A virus (HAV).

By comparing these two viruses that infect the liver, one that is always cleared by the immune system – HAV, and one that frequently evades the immune response – HCV, the team hoped to unravel the mystery of how HCV causes lifelong persistent infections.

Understanding how the immune system responds to HCV is very important because more than 200 million people worldwide and 3.2 million people in the U.S. are chronically infected and at risk for progression to liver cirrhosis and liver cancer. Hepatitis C associated liver disease is the most common indication for liver transplantation, while liver cancer due to HCV infection is now the fastest growing cause of cancer death in the U.S.

“Hepatitis viruses have co-evolved with humans over a very long period of time and they are good at evading the immune system, but nobody understands how hepatitis C becomes a chronic infection,” commented study co-author Stanley M. Lemon, M.D., of UNC.

Hepatitis A virus

Surprisingly, the researchers found that HAV, a relatively benign virus that causes nausea, vomiting and lethargy, and has no chronic state was more adept at evading the innate immune response than HCV.  Examination of the adaptive immune system found that the T cell response to HAV was unique as well. Although the scientists expected the immune response to kill all HAV infected cells in a short time frame, instead they found that the genome of the virus could be detected in the liver for up to one year, long after symptoms of the disease were resolved.

The new study points out the critical need for more information about how the immune system reacts to HCV. It also reinforces the importance of animal research in this instance as the chimpanzee is the only animal model susceptible to HCV infection.

Such research is vital.

Unlike hepatitis A and B for which vaccines are widely available there is no hepatitis C vaccine. There are three basic reasons for this:

• As mentioned above, there is no effective small animal model or cell culture system. This makes vaccine development very challenging because researchers can’t see how the virus really works in a natural environment.
• HCV has different genotypes.  Since hepatitis C has at least six genotypes, several different vaccines would be needed to protect against each genotype.
• HCV mutates very easily. This means that some of its genetic code can change a little bit when it replicates itself. The result is a virus that keeps its genotype, but is different enough to confuse a vaccine.

Come to think of it,  HAV studies aren’t all that easy either. Almost 20 years ago I was peripherally involved with an HAV infectivity study. A biological product I was working with at the time had been implicated in the transmission of  HAV infection.  The suspect product was injected into chimps to see if they would develop the disease.  A second group of chimps housed in cages across the room were not injected, and served as controls. Unfortunately the study had to be terminated early because the test animals started throwing feces at the control group.

Not the outcome we were looking for, but a valuable exercise in the “how not’s” of clinical research!