Oddly enough, Mark and I were recently discussing the apparent lack of
research into finding a cure for this virus. I should have known that,
once we starting talking about it, the news would be full of stories.
Happily, the news seems to be pretty bright.
Hepatitis C
Basics
Hepatitis C is an infection, caused by a virus (HCV), that just
loves liver cells. A member of the Flaviviridae family of
viruses, HCV is related to those that cause yellow fever and dengue.
It is not, however, related to other hepatitis viruses.
The virus settles into the cells of the liver and, when the immune
system sends out white blood cells to attack the virus, the liver
develops inflammation. Over time, usually many years, the
inflammation leads to scarring of the liver tissue. This scarring,
called cirrhosis , causes the liver to stop functioning and
leads to a number of serious complications, even death.
Although they all share the same basic structure, there are a number
of variations or genetic profiles (genotypes) in the hepatitis C
virus. These variations are why it has been, and continues to be,
extremely difficult to develop an effective vaccine.
Depending on the source, there are at least 6 or up to 11 HCV
genetic variations. Within these 6 to 11 genotypes, there are
further variations:
1a - mostly found in North & South America; also common in Australia
1b
- mostly found in Europe and Asia.
2a - is the most common
genotype 2 in Japan and China.
2b - is the most common genotype 2
in the U.S. and Northern Europe.
2c - the most common genotype 2
in Western and Southern Europe.
3a - highly prevalent here in
Australia (40% of cases) and South Asia.
4a - highly prevalent in
Egypt
4c - highly prevalent in Central Africa
5a - highly
prevalent only in South Africa
6a - restricted to Hong Kong,
Macau and Vietnam
7a & 7b - common in Thailand
8a, 8b & 9a
- prevalent in Vietnam
10a & 11a - found in Indonesia
Beyond genotypes 1, 2, and 3, there isn't much information published
about treatment options. As far as the first three, genotype 1 is
the most difficult. It requires a longer treatment period (48+
weeks, compared to 24 weeks), with a very low cure rate; 2 and 3
each average (depending on the source) a 75-80% cure rate.
Treatment News
In a January 6 news release, Merck announced that both the FDA and
the European Medicines Agency (EMA) have granted an accelerated
review / assessment for boceprevir. An oral protease inhibitor[1],
boceprevir is designed for "the treatment of chronic HCV genotype 1
infection, in combination with standard therapy, in adult patients
with compensated liver disease[2] who are
previously untreated or who have failed previous therapy."
What that means is the FDA and EMA both believe that boceprevir
offers a potentially valuable treatment option, unlike anything
currently available for genotype 1 Hep C patients. They have agreed
to expedite the review and approval process to get this critically
needed treatment onto the market. Great news.
Another protease inhibitor, telaprevir has been part of a number of
studies involving more than 2,500 people with genotype 1 HCV. The
studies included patients who had never received treatment, as well
as those who failed to achieve a sustained viral response (SVR) with
standard treatment.
Vertex has been accepted for acclerated assessment by the EMA and is
awaiting a decision from the FDA on a Priority Review.
These two drugs are types of nucleotide analogs[3].
PSI-7977 has been combined with standard treatments (pegylated
interferon and ribavirin) in patients with genotypes 1, 2, and 3.
The primary focus appears to be treatment of individuals with
genotypes 2 and 3.
There were no reports of serious adverse events and, in fact, all
adverse events were consistent with those reported during treatment
with pegylated interferon and ribavirin alone. Even better, all
patients in the study experienced rapid suppression of the virus,
with a viral load below detection limits through the 12 week
treatment period. They will be followed for 24 weeks after
treatment, to monitor SVR.
Additional studies, involving PSI-938 alone and in combination with
PSI-7977, are either underway or enrolling patients.
Bottom Line?
Hepatitis C, first identified in 1979, is a slow-developing virus
that can attack the liver for decades before any symptoms appear. It
is the most common blood-borne infection, and the leading cause of
liver transplantation, in the United States. However, the actual
number of Americans infected with the virus is unknown.
At the beginning of this post, I quoted numbers from one source.
Another, citing a corrected estimate from 2005, indicates 5 million
Americans have been infected and 3.9 million currently have chronic
HCV. The Centers for Disease Control (CDC) posted similar numbers in
2008: "3.2 million persons in the United States have chronic HCV
infection. Infection is most prevalent among those born during
1945–1965, the majority of whom were likely infected during the
1970s and 1980s when rates were highest."
Looking at those dates, one would think that new cases would be few
and far between. However, the facts tell a different story. Due to
the lack of symptoms and little routine testing, it can take decades
for 'new' cases to be reported.
For those of us dealing with Hepatitis C, it's exciting to see the
flurry of activity and the focus on finding a cure; especially for
those suffering with, the difficult to treat, genotype 1.
What isn't mentioned, in all of these news releases about potential
cures, is the
incredible cost of medical care. Estimates put the annual cost
for Americans with chronic Hep C at $9 billion; with a lifetime cost
in the $360 billion range. The cost of liver transplantation alone
is believed to be nearly $300 million per year.
With the current economy, it's not surprising that the State of
Arizona (effective October 1, 2010) no longer covers liver
transplants for patients with HCV. I don't know how many other
states have followed suit. But, the bottom line is pretty obvious.
Patients with chronic Hepatitis C are rapidly running out of
options. We need a cure.
-
Protease
Inhibitor: " A compound that interferes with the ability of
certain enzymes to break down proteins. Some protease inhibitors
can keep a virus from making copies of itself (for example, AIDS
virus protease inhibitors), and some can prevent cancer cells from
spreading."
-
Compensated
Liver Disease: A diseased "liver that can still perform many
of its important functions. Individuals with compensated cirrhosis
may be symptom-free and complication-free; however, this stage of
illness can progress in severity very fast."
-
Nucleotide
Analogs: "Compounds that look like the nucleotides in DNA;
they are used as antiviral compounds because the nucleic acids
assembled with these analogs fall apart. Therefore, the viral
genome cannot be copied and the infection cycle is broken."
