This document discusses hepatitis C virus (HCV) genotypes. It begins by introducing HCV and its effects, noting there are 6 major genotypes. Genotype 1 is most common in the US while genotypes 1, 2, and 3 are found worldwide. Genotype helps determine treatment response, as genotypes 1 and 3 are associated with more aggressive disease. The document then explores molecular genotyping as the "gold standard" method and alternative methods. It concludes by examining how HCV genotype predicts response to interferon-alpha therapy and newer direct-acting antiviral drugs, with genotypes 2 and 3 typically responding better to treatment.

1. GABRIELLE CLARK
November 28,
2017
Viral Genotyping of Hepatit

2. INTRO TO HEPATITIS C
 Hepatitis C virus (HCV) is single-stranded RNA
virus hepacivirus of the Flaviviridae family.
 HCV affects the liver; can lead to: cirrhosis, liver
cancer, and liver failure.
 United States alone, nearly 4 million persons
are infected 1
 30,000 acute new infections are estimated to
occur annually 1
 HCV is responsible for an estimated 8,000 to
10,000 deaths annually in the United States.1
 HCV is the leading reason for liver
transplantation in the US.

3. INTRO TO HEPATITIS C
There are two main types of
hepatitis C:
Acute hepatitis C
Short-term- lasting only six
months or less
Chronic hepatitis C
Can last for one's entire life


4. HCV GENOTYPES
 The ability of the virus to mutate has resulted in the existence of
different genetic variations of HCV
 HCV has six genotypes, labeled 1 through 6.
 There are also subtypes labeled with letters.
HCV Genotype HCV Subtypes
Genotype 1 1a, 1b
Genotype 2 2a, 2b, 2c, 2d
Genotype 3 3a, 3b, 3c, 3d, 3e, 3f
Genotype 4 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h,
4i, 4j
Genotype 5 5a
Genotype 6 6a

5. HCV GENOTYPES
 Genotype 1 is the most
common strain in the
United States.
 Genotypes 1, 2, and 3 are
found worldwide.
 Genotype 4 is found
throughout northern Africa
 Genotype 5 commonly is
found in South Africa.
 Genotype 6 is common in
Asia.

6. HCV GENOTYPES
 Genotype helps to determine treatment
 HCV genotypes respond differently to antiviral treatments due to
substantially differences in genetic make-up.
 Can help predict the outcome
 Genotype 1 and 3 infection are associated with more aggressive
liver disease, with increased risk for cirrhosis. 6

8. “GOLDEN STANDARD”
Molecular Genotyping
1) Genomic amplification
through polymerase chain
reaction
2) Sequencing of a specific
amplified portion of the HCV
genome obtained from the
patient
(NS5, core, E1, and 5’ UTRs
region)
3) Phylogenetic tree analysis
confirmation

9. “GOLDEN STANDARD "LIMITATIONS
1) The amplification of some genomic regions may not be efficient. 2
2) If population template sequencing is employed, the predominant HCV
genotype will be revealed in patients with mixed infection. 2
3) When a large number of isolates are studied, the assignment of some
isolates may not be clear cut. 2
4) Expensive and labor intensive, making it difficult to study HCV
genotypes in a large number of patients.

10. ALTERNATIVE METHODS
1) Amplification with type-specific
primers or type-specific probes. 3
Different HCV types(I to IV)
recognized by the distinct sizes of
their PCR products

11. ALTERNATIVE METHODS
1) Amplification with type-specific
primers or type-specific probes. 3
2) Line probe assay (LiPA)- allows
discrimination of HCV types and
subtypes  capable of detecting
single nucleotide differences in 5’
UTR. 4
Different HCV types(I to IV)
recognized by the distinct sizes of
their PCR products

12. ALTERNATIVE METHODS
2) Line probe assay (LiPA)- allows
discrimination of HCV types and
subtypes  capable of detecting
single nucleotide differences in 5’
UTR. 4

13. HCV GENOTYPE AND RESPONSE
TO THERAPY
HCV genotype is an important viral
factor that has been identified as a
strong independent predictor of
sustained virological response (SVR) to
therapy.
SVR is defined as an undetectable
level of HCV RNA at 12 weeks
(SVR12) or 24 weeks (SVR24) after
completion of treatment.
 HCV genotype has direct clinical
implications for duration and dosage
of combination therapy.

14. HCV GENOTYPE AND RESPONSE
TO THERAPY
An important breakthrough in the treatment of chronic HCV
infection includes standard or pegylated interferon-α (IFN-α)
administered as a monotherapy or in combination with ribavirin.7
Response to IFN-α therapy differs among HCV genotypes
Response rates among patients with genotypes 2 and 3 observed
to be two- to threefold higher than in individuals infected with
genotype 1. 8
The limited efficacy of IFN-α to block viral replication and the
reduced rate of sustained HCV clearance observed in patients
infected with HCV genotype 1. 9
Therapy for patients with infected with genotypes 2 or 3 has been
optimized for a duration of 24 weeks rather than the 48 weeks
10

15. HCV GENOTYPE AND RESPONSE
TO THERAPY
New treatment option - Direct acting antivirals (DAA)- high efficacy
and well-tolerated medications with high cure rates
DAAs are molecules that target specific nonstructural proteins of the virus and
results in disruption of viral replication and infection.
The first approved DAAs, telaprevir and boceprevir, were
introduced in 2011 for the treatment of HCV genotype 1 infection.
Use of telaprevir and boceprevir in combination with pegylated
IFN-α and ribavirin  led to achievement of SVR rates in 65%–75%
of patients with HCV genotype 1. 11

16. Treatment durations are adapted from the 2015 guidelines of the American Association for the
Study of Liver Diseases (AASLD) (50) and European Association for the Study of the Liver (EASL)
(51).

17. Thank
You

18. REFERENCES
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