Originally Published June 15, 2015
This month’s column is about hepatitis C (HCV)
genotypes. I will discuss genotypes 1, 2, 3, 4, and 6. You will
notice that I am not discussing genotype 5 since it is discussed
elsewhere in this issue. Genotype 7 is also not being discussed because
only three people with genotype 7 have been identified—all found to be
from the Democratic Republic of Congo.
According to the World Health
Organization 130 – 150 million people worldwide have chronic hepatitis C
and 350,000 – 500,000 die every year from complications of hepatitis
As mentioned above there have
been seven genotypes identified but there are likely more that have not
yet been found or classified. There is a 30 to 35% viral diversity
or difference in the genetic make-up of the nucleotide sites of the
virus that are used to classify them as different genotypes. This viral
diversity is what makes it so difficult to develop one drug to treat
all of the genotypes. There are new drugs called pan-genotypic that
work on all of the genotypes that are being developed that might just
produce high cure rates across all of the genotypes. The viral
diversity i.e. genotype is another reason why it is going to be
difficult to develop a therapeutic or a protective vaccine. There has
been some early research that is encouraging.
All evidence points to that the
hepatitis C virus originated in Africa and spread throughout Africa by
various routes including the European colonization of Africa, unsafe
medical practices to treat tropical diseases and various cultural
practices. HCV spread out of Africa occurred by way of the slave trade
throughout the World, needle reuse, organ transplantation, unsafe
medical practices, unscreened blood, and injection drug use, etc.
Genotype 1 is the most common genotype worldwide and
accounts for approximately 46% of the total number of people with
hepatitis C worldwide —83 million people. The prevalence of genotype 1
expanded greatly during the 20th century due to unsafe blood
product/organ transplantation, unsafe medical practices and injection
Countries with the highest
prevalence include East Asia (32,082,000), South Asia (12,889,000),
Southeast Asia (4,910,000), Western sub-Sahara Africa (4,427,000),
Eastern Europe (4,023,000), Central Latin America (2,796,000), Central
Genotype 1 has two main subtypes 1a and 1b. Genotype
1a accounts for about 55% of those with genotype 1 in the U.S. and 45%
of those with genotype 1b. HCV 1a is more difficult to treat than HCV
genotype 1b. The current standard of care for treating HCV genotype 1
can cure up to 90% to 100% of people who take the medications. The
current standard of care treatment is HARVONI and VIEKIRA PAK.
Genotype 1 subtypes c through l have been identified but are uncommon
Genotype 2 is the 3rd most common genotype worldwide
and is also the 3rd most common one in the United States. The areas
of highest prevalence of genotype 2 worldwide include central Latin
America (754,000), high-income Asia Pacific (629,000), Southeast Asia
(1,572,000), East Asia (8,444,000), Western sub-Saharan African
(1,550,000) and western Europe (583,000). Genotype 2 accounts for more
than 16.5 million people worldwide with hepatitis C.
Genotype 2 spread through the
slave trade from Africa to the Americas and through trade routes from
the Africa, the America and Asia.
The most common subtypes of genotype 2 are 2a, 2b, and 2c, so far there have been another 15 subtypes identified.
The standard of care for
treating HCV genotype 2 is the combination of Sovaldi (sofosbuvir) plus
ribavirin for a treatment duration of 12 weeks. The cure rates are
88% to 97%.
Genotype 3 is the 2nd most common genotype in the
United States and worldwide. The areas with the highest prevalence of
genotype 3 include Australasia (280,000), Central Asia (906,000), East
Asia (5,762,000), Eastern Europe (1,881,000), High Income North America
(492,000), and South Asia (39,706,000). The total number of people
worldwide with genotype 3 is 54 million.
Genotype 3 has been found to
exist for 200 years. Genotype 3 causes steatosis (fatty liver), insulin
resistance (precursor of type 2 diabetes), and increases the risk of
HCV disease progression and liver cancer.
So far there have been 10 genotype 3 subtypes identified—subtype 3a is the most common.
The current standard of care to
treat genotype 3 is the combination of Sovaldi and ribavirin for a
treatment period of 24 weeks. The cure rates are up to 83%. However,
Sovaldi plus ribavirin doesn’t work as well in genotype 3 people with
cirrhosis who are treatment experienced. There are, however, very good
treatment options (see article in this issue on Sovaldi, pegylated
interferon and ribavirin) and many new drugs are being developed to
treat genotype 3.
Genotype 4 is the 4th most common genotype worldwide
and accounts for 90% (6,030,000) of the hepatitis C population in
Egypt—The HCV population of Egypt is estimated at 6.7 million. Africa
and the Middle East account for the majority of genotype 4 infections.
Approximately 1% of the U.S. population has genotype 4. Genotype 4
has many subtypes – a through o.
In Egypt the spread of hepatitis
C genotype 4 was the result of a mass campaign in the 1960’s through
the 1980’s to control schistosomiasis infection—a parasitic disease
transferred by snails to humans wading in water while working in rice
fields. During the 1960’s through the 1980’s people infected with
schistosomiasis were treated with drugs using unsterilized and re-used
The current standard of care for
treating HCV genotype 4 is the combination of Sovaldi (sofosbuvir),
pegylated interferon and ribavirin. The treatment duration is 12
weeks and cure rates are up to 96%. There are many drugs that have
been developed to treat genotype 4—by AbbVie and Merck—that are likely
to be approved in the near future.
Genotype 6 is mostly seen in Southeast Asia. The
estimated number of people who are infected with genotype 6 is about
10,000,000—mostly in Asia. It is the most prevalent genotype in Laos
and one of the most common genotypes in Vietnam. Genotype 6 is seen in
countries outside of Asia, but mainly in populations that have
emigrated from Asian countries.
Genotype 6a is the most common, but there been 26 subtypes identified so far.
There is no standard of care to
treat genotype 6. In a study of 25 people who took Harvoni (sofosbuvir
plus ledipasvir) for a treatment period of 12 weeks to treat genotype 6
resulted in a cure rate of 82%. The study included people who had
never been treated and people who had been treated but had not been
cured. There are many other drugs in development to treat genotype 6
including Merck’s combination of grazoprevir/elbasvir.
The future is bright for the
treatment of hepatitis C with more awareness of all of the HCV
genotypes worldwide. There are many drugs under development to treat
hepatitis C that are even more effective. Many of the newer drugs in
development are pan-genotypic—that is they work against all genotypes
and have the potential to cure all genotypes—these drugs could provide
cures worldwide if we could only identify and treat everyone.
Labels: Genotypes, The Five