Self-Recovery of Hepatitis C: It May be About Genetics
by John C. Martin


Why do some people with hepatitis C need continuous treatment, and others
spontaneously recover with no treatment at all? It's a question that has dogged
scientists in the hepatitis community.

Now, in a study published in early August,1 researchers at Johns Hopkins
University have found that people's genes play an important part in whether or
not they recover from the viral infection. These are genes involved in the
suppressing the body’s defensive “killer” immune cells. This genetic factor was
found in people assumed to be exposed to a low dose of virus at the time they
were infected.

What's In Your Genes?
“Our findings may help explain why some of the 20 percent of people infected
with hepatitis C manage to recover on their own, while the remaining 80 percent
remain infected and may need treatment,” said Chloe Thio, MD, an assistant
professor of medicine at Johns Hopkins University, and one of this study’s lead
authors.

In making this discovery, the scientists say they hope it will one day lead to
the development of a vaccine, and improve current therapies for hepatitis C.

“Hepatitis C infection is a serious disease with few treatments, and it takes a
heavy toll among disadvantaged Americans, including those who have weakened
immune systems and are HIV positive,” Thio said. “Our results were surprising in
that self-recovery is not so much a function of speeding up the body’s immune
system to attack the hepatitis C virus, as it is about taking the foot off the
brakes so the body’s killer immune cells can take off.”

Current Therapy Protocol
Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). It’s found
in the blood of person’s who have the disease, and is spread through contact
with blood from an infected person. Combination therapy with pegylated (a longer
lasting) interferon and the anti-viral medication, ribavirin, is the treatment
of choice which results in sustained response rates of 40% to 80%, experts say.
Interferon monotherapy is also an option generally reserved for patients in whom
ribavirin is not advisable.2

According to statistics, up to 85 percent of people with HCV may develop
long-term infection, and a certain percentage may also develop cirrhosis over a
period of 20 to 30 years.2

What's the Common Denominator?
Thio and her research team from England’s Southampton University and the
National Cancer Institute analyzed DNA from blood samples taken from more than
1,000 patients infected with hepatitis C, of whom 350 recovered on their own
without medication. Thio and her colleagues were able to compare the genetic
characteristics that were more common between those who self-recovered and those
who did not.

The common trait in people who self-recover lies in a group of genes for a key
protein—a receptor known as KIR2DL3—as well as other specific genes. This unique
melding of genetics was active in those lucky enough to be homozygous
(homo-ZYE-gus). That means two copies of the gene, one from each parent, were
required for the patient to possess the ability to recover from HCV. If not,
self-recovery didn't occur.

In those patients with a presumed low viral load, such as those infected by a
contaminated drug or tattoo needles instead of a blood transfusion, two copies
of the gene combination were found in 20 percent of those who self-recovered,
but only half that percentage among those who did not self-recover and needed
medications, Thio and her associates found.

What Does This Unique Protein Do?
A significant function of this related protein is its ability to roadblock the
action of the body’s killer immune cells, serving as a chemical signal for these
cells in keeping them away from the body’s healthy cells. On the other hand,
when this protein is not keeping the immune system in check, the killer immune
cells jump into action, and get rid of unwanted cells in the body, such as
bacteria and viruses like hepatitis.

The researchers zeroed in specifically on the genes involved with killer immune
cells because earlier studies in animals had shown that natural killer cells
were more active in those who self-recovered compared to those who did not
recover spontaneously.

“It remains to be explained how these genes and viral dose at the time of
infection interact in determining self-recovery from hepatitis C,” Thio pointed
out. “It can only be hypothesized at this point that high-dose infections
possibly overwhelm the body’s killer immune system, whereas low-dose infections
do not.”

This research, therefore, spotlights the process that activates or de-activates
the “inhibitory signals” of the immune response, added David Thomas, MD, a study
investigator and professor of medicine at Hopkins. “Whether it is possible to
manipulate these very specific signals to promote recovery from hepatitis C
remains to be seen,” he said.

1. Khakoo SI, Thio CL, Martin MP et al. HLA and NK cell inhibitory receptor
genes in resolving hepatitis C virus infection. Science 2004 Aug
6;305(5685):872-4.
2. National Center for Infectious Diseases. Centers for Disease Control and
Prevention (CDC). Frequently Asked Questions About Hepatitis C.





Sandra Tara Balduf (Ane)

Frontline Hepatitis Awareness

Support for patients and educational materials

http://frontline-hepatitis-awareness.com

1-866-Hep-GoGo 866-437-4646




[Non-text portions of this message have been removed]