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The Role Of Genetics In Hepatitis
Susceptibility and Treatment
Response
Presented By: Hina Aftab
Learning
Objectives
What is Hepatitis
Role of Genetics in Hepatitis Susceptibility
(Genetic Polymorphisms, HLA Genes)
Hepatitis Treatment Response
(Interferon-Based Therapy, DAA Therapy)
Future Perspectives of Pharmacogenomics and
Personalized Medicine
Challenges and Limitations
What is
Hepatitis?
Hepatitis, a viral infection causing inflammation
of the liver, affects millions of people worldwide.
 Genetic factors play a crucial role in determining
an individual's susceptibility to hepatitis and their
response to treatment.
 Let's delve into the details.
What is
Hepatitis?
 The disease can be caused by several viruses,
including hepatitis A, B, C, D, and E.
 While environmental factors such as exposure to
infected blood or body fluids play a significant
role in hepatitis transmission, genetics also
influence an individual's susceptibility to the
disease and their response to treatment.
 Understanding the genetic factors involved can
help personalize treatment approaches and
improve patient outcomes.
Hepatitis
Susceptibility
The following factors plays an important
role in hepatitis Susceptibility.
1)Genetic Polymorphisms
2)HLA Genes
3)Innate Immune Response Genes
4)Cytokine and Interferon Genes
5)Viral Entry and Receptor Genes
6)Genetic Interactions with Environmental Factors
Genetic
Polymorphisms
Polymorphisms in genes such as IFNL3
(interferon lambda 3) and IL28B (interleukin
28B) are associated with spontaneous clearance of
HCV infection.
Variants in IL28B gene predict treatment response
to interferon-based therapy in HCV patients.
Polymorphisms in genes related to viral entry,
immune response, and inflammation pathways
contribute to hepatitis susceptibility.
HLAGenes
The Human Leukocyte Antigen (HLA) genes
encode proteins responsible for immune system
regulation.
Variations in HLA genes have been associated
with increased susceptibility to hepatitis B and C
viruses (HBV and HCV).
HLA-B57 and HLA-C01 alleles have been
linked to increased HBV clearance, while HLA-
DP and HLA-DQ alleles influence HCV
susceptibility.
Innate Immune
Response
Genes
Genes involved in the innate immune response,
such as Toll-like receptors (TLRs), have been
associated with hepatitis susceptibility.
Polymorphisms in TLR genes, including TLR2,
TLR3, TLR4, and TLR9, have been linked to
altered immune responses and increased
susceptibility to viral hepatitis.
Cytokine and
Interferon
Genes
 Genetic variations in cytokine and interferon genes have
been implicated in hepatitis susceptibility.
 Polymorphisms in genes encoding pro-inflammatory
cytokines, such as interleukin-6 (IL-6) and tumor
necrosis factor-alpha (TNF-α), have been associated with
increased risk of HBV and HCV infection.
 Additionally, genetic variants in interferon regulatory
factor 5 (IRF5) and interferon alpha receptor 1
(IFNAR1) have been linked to increased susceptibility to
HCV infection.
Viral Entry
and Receptor
Genes
Genes encoding viral entry receptors play a critical
role in determining hepatitis susceptibility.
For example, variations in the NTCP receptor
gene, which is essential for HBV entry, have been
associated with altered susceptibility to HBV
infection.
Similarly, polymorphisms in CD81, a receptor for
HCV entry, have been implicated in HCV
susceptibility.
Genetic
Interactions with
Environmental
Factors
1) Viral Factors:
Genetic variations can interact with viral factors to
influence hepatitis susceptibility.
 For example, certain HBV genotypes have been
associated with increased hepatocellular
carcinoma risk, especially when combined with
specific viral variants, such as precore and core
promoter mutations.
Interactions between host and viral factors shape
disease outcomes.
Genetic
Interactions with
Environmental
Factors
2)Host-Environment Interactions:
Environmental factors, such as alcohol
consumption, smoking, and exposure to
hepatotoxic substances, can interact with host
genetic factors to modulate hepatitis
susceptibility and disease progression.
 Gene-environment interactions may contribute
to individual differences in disease outcomes and
treatment responses, highlighting the need for a
comprehensive approach in understanding
hepatitis genetics.
Hepatitis
Treatment
Response
For the effective Treatment & management of
Hepatitis the following methods are used commonly.
1)Interferon-Based Therapy
2)Direct-Acting Antiviral (DAA) Therapy
Genetics plays an important role in the effectiveness of
the above mentioned treatment methods.
Interferon-Based
Therapy
Polymorphisms in IL28B gene influence the
response to interferon-based therapy for HCV.
Individuals with favorable IL28B genotypes
(e.g., CC genotype) show higher sustained
virological response rates.
Genetic testing for IL28B variants helps
personalize treatment decisions.
Direct-Acting
Antiviral (DAA)
Therapy
DAA therapy revolutionized the treatment of
chronic hepatitis C.
Polymorphisms in genes encoding drug-
metabolizing enzymes (e.g., CYP450) affect
drug metabolism and treatment response.
Genetic variations in genes like MBL2
(mannose-binding lectin 2) and TLR3 (Toll-like
receptor 3) influence DAA response.
Pharmacogenomics
and Personalized
Medicine
Pharmacogenomics focuses on the study of how
genetic variations impact drug response.
In the context of hepatitis treatment,
pharmacogenomics plays a crucial role in
personalizing medicine.
 By identifying genetic markers associated with
treatment response, clinicians can optimize drug
selection, dosage, and treatment duration.
Future
Perspectives
Advancements in genome sequencing
technologies enable comprehensive genetic
profiling for personalized medicine.
Identification of novel genetic variants associated
with hepatitis susceptibility and treatment
response is an active area of research.
Integration of genetic information with clinical
data will enhance treatment outcomes and
improve patient care.
Challenges
and
Limitations
While genetics plays a significant role in hepatitis
susceptibility and treatment response, several
challenges and limitations must be addressed.
 Genetic testing for personalized medicine
approaches can be costly and not readily
accessible in all healthcare settings.
 Furthermore, the complexity of genetic
interactions and the influence of environmental
factors require further research to validate genetic
markers and optimize treatment guidelines.
Conclusion
In conclusion, genetics plays a vital role in
determining an individual's susceptibility to
hepatitis and their response to treatment.
Understanding genetic variations associated with
hepatitis susceptibility and treatment response
allows for personalized medicine approaches and
improved therapeutic outcomes.
Conclusion
Furthermore, genetic markers such as those in the
IL28B gene have been identified as strong
predictors of treatment response to interferon-
based therapy and DAAs in HCV patients.
The integration of pharmacogenomics into
clinical practice holds great promise for
advancing hepatitis treatment and moving
towards personalized medicine.
By leveraging genetic information, we can
enhance prevention strategies, optimize treatment
choices, and improve the overall management of
hepatitis.
Advances in Virology presentaion #2.pptx

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Advances in Virology presentaion #2.pptx

  • 1. The Role Of Genetics In Hepatitis Susceptibility and Treatment Response Presented By: Hina Aftab
  • 2. Learning Objectives What is Hepatitis Role of Genetics in Hepatitis Susceptibility (Genetic Polymorphisms, HLA Genes) Hepatitis Treatment Response (Interferon-Based Therapy, DAA Therapy) Future Perspectives of Pharmacogenomics and Personalized Medicine Challenges and Limitations
  • 3. What is Hepatitis? Hepatitis, a viral infection causing inflammation of the liver, affects millions of people worldwide.  Genetic factors play a crucial role in determining an individual's susceptibility to hepatitis and their response to treatment.  Let's delve into the details.
  • 4. What is Hepatitis?  The disease can be caused by several viruses, including hepatitis A, B, C, D, and E.  While environmental factors such as exposure to infected blood or body fluids play a significant role in hepatitis transmission, genetics also influence an individual's susceptibility to the disease and their response to treatment.  Understanding the genetic factors involved can help personalize treatment approaches and improve patient outcomes.
  • 5. Hepatitis Susceptibility The following factors plays an important role in hepatitis Susceptibility. 1)Genetic Polymorphisms 2)HLA Genes 3)Innate Immune Response Genes 4)Cytokine and Interferon Genes 5)Viral Entry and Receptor Genes 6)Genetic Interactions with Environmental Factors
  • 6. Genetic Polymorphisms Polymorphisms in genes such as IFNL3 (interferon lambda 3) and IL28B (interleukin 28B) are associated with spontaneous clearance of HCV infection. Variants in IL28B gene predict treatment response to interferon-based therapy in HCV patients. Polymorphisms in genes related to viral entry, immune response, and inflammation pathways contribute to hepatitis susceptibility.
  • 7. HLAGenes The Human Leukocyte Antigen (HLA) genes encode proteins responsible for immune system regulation. Variations in HLA genes have been associated with increased susceptibility to hepatitis B and C viruses (HBV and HCV). HLA-B57 and HLA-C01 alleles have been linked to increased HBV clearance, while HLA- DP and HLA-DQ alleles influence HCV susceptibility.
  • 8. Innate Immune Response Genes Genes involved in the innate immune response, such as Toll-like receptors (TLRs), have been associated with hepatitis susceptibility. Polymorphisms in TLR genes, including TLR2, TLR3, TLR4, and TLR9, have been linked to altered immune responses and increased susceptibility to viral hepatitis.
  • 9. Cytokine and Interferon Genes  Genetic variations in cytokine and interferon genes have been implicated in hepatitis susceptibility.  Polymorphisms in genes encoding pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), have been associated with increased risk of HBV and HCV infection.  Additionally, genetic variants in interferon regulatory factor 5 (IRF5) and interferon alpha receptor 1 (IFNAR1) have been linked to increased susceptibility to HCV infection.
  • 10. Viral Entry and Receptor Genes Genes encoding viral entry receptors play a critical role in determining hepatitis susceptibility. For example, variations in the NTCP receptor gene, which is essential for HBV entry, have been associated with altered susceptibility to HBV infection. Similarly, polymorphisms in CD81, a receptor for HCV entry, have been implicated in HCV susceptibility.
  • 11. Genetic Interactions with Environmental Factors 1) Viral Factors: Genetic variations can interact with viral factors to influence hepatitis susceptibility.  For example, certain HBV genotypes have been associated with increased hepatocellular carcinoma risk, especially when combined with specific viral variants, such as precore and core promoter mutations. Interactions between host and viral factors shape disease outcomes.
  • 12. Genetic Interactions with Environmental Factors 2)Host-Environment Interactions: Environmental factors, such as alcohol consumption, smoking, and exposure to hepatotoxic substances, can interact with host genetic factors to modulate hepatitis susceptibility and disease progression.  Gene-environment interactions may contribute to individual differences in disease outcomes and treatment responses, highlighting the need for a comprehensive approach in understanding hepatitis genetics.
  • 13. Hepatitis Treatment Response For the effective Treatment & management of Hepatitis the following methods are used commonly. 1)Interferon-Based Therapy 2)Direct-Acting Antiviral (DAA) Therapy Genetics plays an important role in the effectiveness of the above mentioned treatment methods.
  • 14. Interferon-Based Therapy Polymorphisms in IL28B gene influence the response to interferon-based therapy for HCV. Individuals with favorable IL28B genotypes (e.g., CC genotype) show higher sustained virological response rates. Genetic testing for IL28B variants helps personalize treatment decisions.
  • 15. Direct-Acting Antiviral (DAA) Therapy DAA therapy revolutionized the treatment of chronic hepatitis C. Polymorphisms in genes encoding drug- metabolizing enzymes (e.g., CYP450) affect drug metabolism and treatment response. Genetic variations in genes like MBL2 (mannose-binding lectin 2) and TLR3 (Toll-like receptor 3) influence DAA response.
  • 16. Pharmacogenomics and Personalized Medicine Pharmacogenomics focuses on the study of how genetic variations impact drug response. In the context of hepatitis treatment, pharmacogenomics plays a crucial role in personalizing medicine.  By identifying genetic markers associated with treatment response, clinicians can optimize drug selection, dosage, and treatment duration.
  • 17. Future Perspectives Advancements in genome sequencing technologies enable comprehensive genetic profiling for personalized medicine. Identification of novel genetic variants associated with hepatitis susceptibility and treatment response is an active area of research. Integration of genetic information with clinical data will enhance treatment outcomes and improve patient care.
  • 18. Challenges and Limitations While genetics plays a significant role in hepatitis susceptibility and treatment response, several challenges and limitations must be addressed.  Genetic testing for personalized medicine approaches can be costly and not readily accessible in all healthcare settings.  Furthermore, the complexity of genetic interactions and the influence of environmental factors require further research to validate genetic markers and optimize treatment guidelines.
  • 19. Conclusion In conclusion, genetics plays a vital role in determining an individual's susceptibility to hepatitis and their response to treatment. Understanding genetic variations associated with hepatitis susceptibility and treatment response allows for personalized medicine approaches and improved therapeutic outcomes.
  • 20. Conclusion Furthermore, genetic markers such as those in the IL28B gene have been identified as strong predictors of treatment response to interferon- based therapy and DAAs in HCV patients. The integration of pharmacogenomics into clinical practice holds great promise for advancing hepatitis treatment and moving towards personalized medicine. By leveraging genetic information, we can enhance prevention strategies, optimize treatment choices, and improve the overall management of hepatitis.