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HCV BASICS
Pre esproute
What are the types of viral hepatitis ?
Hepatitis C
 Hepatitis C is a type of viral hepatitis or
inflammation of the liver caused by the Hepatitis
C virus
Structure of the Hepatitis C virus (HCV)
•HCV virus is enveloped spherical shaped enveloped, liver RNA virus
•Single-stranded RNA as genetic material
•Exists in 7 genotypes(1-7) or genetic structures
•It has a with a lipid envelope (E) containing glycoproteins (E1 and
E2) and a core of capsid proteins
Single strand of
RNA
HCV RNA structure
•The viral RNA forms 3 structural proteins and 7 nonstructural proteins (see fig. above)
•3 structural proteins (core, E1, E2) and seven non-structural proteins (p7/NS1,
NS2, NS3, NS4A, NS4B, NS5A, and NS5B)
•The non structural proteins are important for performing functions
•The structural proteins help in forming structure of the virus
Global HCV Disease burden
 Significant global impact
 3-4 million persons are newly infected each year
 130-170 million people are HCV infected
 HCV: Leading cause of liver transplantation
 27% of cirrhosis and 25% of liver cancer is due to
hepatitis C worldwide
1. Abstract 23; Benjamin C. Cowie et al. Presented at the 64th AASLD meeting, Nov 1-5, 2013; Washington
2. J Hepatol 2006;45:529-538.
3. Hepatology 2013;57:1333-1342
4. J. Biosci. 2008;33 465–473.
5. Indian J Gastroenterol 1998;17:100 –3.
Global HCV Disease burden
Abstract 23; Benjamin C. Cowie et al. Presented at the 64th AASLD meeting, Nov 1-5, 2013; Washington,
Global distribution - HCV genotypes
 HCV virus can be classified into seven recognized
genotypes or genetic structures (1–7) on the basis of
the sequence of amino acids in the HCV
 HCV genotype 1 is the most prevalent worldwide,
comprising 83.4 million cases (46.2% of all HCV
cases)
 Genotype 3 is the next most prevalent globally (54.3
million, 30.1%)
. Mesina J. et al Hepatology. 2014 Jul 28. doi: 10.1002/hep.27259.
Prevalence of HCV genotype
Hepatology. 2014 Jul 28. doi: 10.1002/hep.27259.
Majority of infected patients have HCV genotype 1 worldwide (seen in
red)
However in India, majority of HCV is due to HCV genotype 3 (seen in
green)
Indian Scenario- Prevalence
 The prevalence of HCV infection in India is estimated at
between 0.5% and 1.5% (15-18 million)
 It is higher in the north-eastern part, tribal populations
and Punjab, and is lower in the western and eastern
parts of the country
 Genotype 3 is the most common HCV genotype in
India (accounting for 54–80% of cases), followed by
genotype 1
 Genotype 1 has been reported more commonly from
southern India
Journal of Clinical and Experimental Hepatology 2014; 4(2):106–116.
Routes of transmission of HCV
The spread of hepatitis C infection is by parenteral route
(through infected blood) and sources of infection include
HCV is
believed to be
spread in India
mainly through
unsafe blood
banking and
reuse of
injection
needles
• Transfusion of blood and especially blood products
• Injection/I.V drug abuse
• Occupational exposure to blood (2-10%)
• Sharing razors, toothbrushes (infected with blood)
• Mother to baby (during pregnancy or at birth; usually
infection is mild and free of symptoms)
• Sexual transmission not as common as it is with
hepatitis B virus
Routes of transmission of
HCV
Routes of transmission of HCV:
Contaminated sharps/needles Contaminated
sharps/needles
Signs and Symptoms of HCV
 Most patients are asymptomatic
or have very mild non-specific
symptoms
 Fatigue or tiredness may be
prominent
 Other symptoms include mild
fever, muscle and joint aches,
nausea, vomiting, loss of
appetite, abdominal pain, and
sometimes diarrhea
Signs and Symptoms of HCV
 When patients develop
symptomatic acute HCV
infection, they most often
present with dark urine
and light colored stools,
followed by jaundice in
which the skin and whites
of the eyes appear yellow.
 Itching of the skin may be
present.
 On average, symptoms
appear 6 to 7 weeks after
infection
Itching of the skin
Who should be screened for Hepatitis C ?
High-Risk Populations
 People who inject drugs
 Recipients of infected blood products or invasive procedures in
health-care facilities with inadequate infection control practices
 Children born to mothers infected with HCV
 People with sexual partners who are HCV-infected
 People with HIV infection
 Prisoners/People who have had tattoos or piercings
 Healthcare, emergency medical, and public safety workers
after needle sticks, sharps, or mucosal exposures to HCV-
infected blood;
 Patients suffering from Thalassemia
 Kidney disease patients receiving long-term hemodialysis
 Unexplained long term liver disease and hepatitis including
high liver enzymes
What is thalessemia?
 Thalassemia is an genetic blood disorder in which the body makes
an abnormal form of hemoglobin
 Hemoglobin is the protein molecule in red blood cells that carries
oxygen
 The disorder results in excessive destruction of red blood cells,
which leads to anemia
 Anemia is a condition in which your body doesn’t have enough
normal, healthy red blood cells
 These patients may need repeated blood transfusions and hence
are prone to HCV infection
What is hemodialysis ?
 Hemodialysis is a treatment for kidney failure that
uses a machine to filter blood outside the body
 It is a process of purifying the blood of a person
whose kidneys are not working normally
 The blood travels through the tube to the filter,
called a dialyzer
 Inside the dialyzer, the blood flows through thin
fibers that filter out
 wastes
 extra salt
 extra fluid
 After the dialyzer filters the blood, a different tube
carries your blood back to the body
 HCV infection may be common in these patients
due to lack of standard infection control practices,
physical proximity to an infected patient, and
sharing of dialysis machines
Disease Progression of HCV
 Hepatitis C virus causes both acute and chronic infection
 Acute HCV infection is defined as the presence of HCV within six
months of exposure to HCV
 Of every 100 people infected with the virus, about:
 15–25 clear the virus without treatment (in the first six months after
getting Hep C)
 75–85 develop a long-term infection
 70 develop chronic liver disease
 10–20 develop cirrhosis (scarring of the liver) over a period of 20
to 30 years
 1–5 will die of liver cirrhosis, or liver cancer
How does HCV infection
progress?
Progression to cirrhosis may
be increased by older age,
obesity, immunosuppression,
or consumption of excessive
alcohol
Hepatology. 2009;49:1335-74.
•Mostly normal
functioning of liver
(Minimal impairment )
•Few or no symptoms
•LFT normal
•Abnormal functioning of
liver
•Symptoms present/
complications of cirrhosis
seen
•LFT abnormal
How does liver status progress
HCV infection?
Diagnosis of HCV
Screening test for HCV
 Doctors use a blood test, called a Hepatitis C Antibody Test or
Anti-HCV Test, to find out if a person has ever been infected with
Hepatitis C
 This test looks for antibodies to the Hepatitis C virus
 Antibodies are chemicals released into the bloodstream when
someone gets infected
 Once people have been infected, they will always have antibodies
in their blood even if they have been cured of the Hepatitis C virus
Diagnosis of HCV
A non-reactive or negative
antibody test
means that a person does not
have Hepatitis C.
However, if a person has been
exposed to the Hepatitis C virus in
the last 6 months, he or she will
need to be tested again
Reactive or Positive Hepatitis C
Antibody Test
means that Hepatitis C antibodies
were found in the blood and a
person has been infected with the
Hepatitis C virus at some point in
time
Diagnosis of HCV
 If the antibody test is reactive or positive, an additional blood test
is needed to determine if a person is currently infected with
Hepatitis C
 This test is called a HCV RNA test : confirmatory test for HCV
 This test cannot differentiate between acute and chronic infection
HCV RNA test is negative HCV RNA test is positive
Person does not have Hepatitis C Person currently has Hepatitis C
Consult the doctor
HCV antibody test positive
Other tests
Other blood tests
If an initial blood test shows that you have hepatitis
C, additional blood tests are:
 Measure the quantity of the hepatitis C virus in the
blood (viral load)
 Identify the genotype of the virus: indicates the
strain of the virus and is used in making decisions
about treatment
Other tests
Tests for liver damage
 transient elastography, a special ultrasound of the
liver where a image of the liver can be seen on the
screen to assess the extent of liver damage
 liver biopsy, in which a doctor uses a needle to
take a small piece of tissue from the liver which is
examined under a microscope to look for liver
damage
Transient elastography Liver biopsy
Treatment
 The goal of treatment is to have no hepatitis C virus detected in
your body at least 12 weeks after you complete treatment also
called as cure
 The cure rate depends on several factors including the genotype of
the virus and the type of treatment given
 The standard of care for hepatitis C is changing rapidly
 Earlier weekly injections of interferons were administered with daily
oral ribavirin (antiviral drug) for as long as 6-12 months
 These medications cured only 40- 70% of patients depending on
the HCV genotype
 There remains a limited role for pegylated interferon and ribavirin
with the entry of newer drugs called as directly acting antivirals
(DAAs)
Treatment : Directly acting
antivirals
 Directly acting antivirals : Sofosbuvir, daclatasvir ,
sofosbuvir-ledipasvir and sofosbuvir-velpatasvir fixed
dose combination are part of the preferred regimens,
and can achieve cure rates above 95%
 Directly acting antivirals or DAAs and are much more
effective, safer and better-tolerated than the older
therapies
 Therapy with DAAs can cure most persons with HCV
infection and treatment is shorter (usually 12 weeks)
 There is currently no vaccine to prevent hepatitis C
END

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Basics of Hepatitis C

  • 2. What are the types of viral hepatitis ?
  • 3. Hepatitis C  Hepatitis C is a type of viral hepatitis or inflammation of the liver caused by the Hepatitis C virus
  • 4. Structure of the Hepatitis C virus (HCV) •HCV virus is enveloped spherical shaped enveloped, liver RNA virus •Single-stranded RNA as genetic material •Exists in 7 genotypes(1-7) or genetic structures •It has a with a lipid envelope (E) containing glycoproteins (E1 and E2) and a core of capsid proteins Single strand of RNA
  • 5. HCV RNA structure •The viral RNA forms 3 structural proteins and 7 nonstructural proteins (see fig. above) •3 structural proteins (core, E1, E2) and seven non-structural proteins (p7/NS1, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) •The non structural proteins are important for performing functions •The structural proteins help in forming structure of the virus
  • 6. Global HCV Disease burden  Significant global impact  3-4 million persons are newly infected each year  130-170 million people are HCV infected  HCV: Leading cause of liver transplantation  27% of cirrhosis and 25% of liver cancer is due to hepatitis C worldwide 1. Abstract 23; Benjamin C. Cowie et al. Presented at the 64th AASLD meeting, Nov 1-5, 2013; Washington 2. J Hepatol 2006;45:529-538. 3. Hepatology 2013;57:1333-1342 4. J. Biosci. 2008;33 465–473. 5. Indian J Gastroenterol 1998;17:100 –3.
  • 7. Global HCV Disease burden Abstract 23; Benjamin C. Cowie et al. Presented at the 64th AASLD meeting, Nov 1-5, 2013; Washington,
  • 8. Global distribution - HCV genotypes  HCV virus can be classified into seven recognized genotypes or genetic structures (1–7) on the basis of the sequence of amino acids in the HCV  HCV genotype 1 is the most prevalent worldwide, comprising 83.4 million cases (46.2% of all HCV cases)  Genotype 3 is the next most prevalent globally (54.3 million, 30.1%) . Mesina J. et al Hepatology. 2014 Jul 28. doi: 10.1002/hep.27259.
  • 9. Prevalence of HCV genotype Hepatology. 2014 Jul 28. doi: 10.1002/hep.27259. Majority of infected patients have HCV genotype 1 worldwide (seen in red) However in India, majority of HCV is due to HCV genotype 3 (seen in green)
  • 10. Indian Scenario- Prevalence  The prevalence of HCV infection in India is estimated at between 0.5% and 1.5% (15-18 million)  It is higher in the north-eastern part, tribal populations and Punjab, and is lower in the western and eastern parts of the country  Genotype 3 is the most common HCV genotype in India (accounting for 54–80% of cases), followed by genotype 1  Genotype 1 has been reported more commonly from southern India Journal of Clinical and Experimental Hepatology 2014; 4(2):106–116.
  • 11. Routes of transmission of HCV The spread of hepatitis C infection is by parenteral route (through infected blood) and sources of infection include HCV is believed to be spread in India mainly through unsafe blood banking and reuse of injection needles • Transfusion of blood and especially blood products • Injection/I.V drug abuse • Occupational exposure to blood (2-10%) • Sharing razors, toothbrushes (infected with blood) • Mother to baby (during pregnancy or at birth; usually infection is mild and free of symptoms) • Sexual transmission not as common as it is with hepatitis B virus
  • 13. Routes of transmission of HCV: Contaminated sharps/needles Contaminated sharps/needles
  • 14. Signs and Symptoms of HCV  Most patients are asymptomatic or have very mild non-specific symptoms  Fatigue or tiredness may be prominent  Other symptoms include mild fever, muscle and joint aches, nausea, vomiting, loss of appetite, abdominal pain, and sometimes diarrhea
  • 15. Signs and Symptoms of HCV  When patients develop symptomatic acute HCV infection, they most often present with dark urine and light colored stools, followed by jaundice in which the skin and whites of the eyes appear yellow.  Itching of the skin may be present.  On average, symptoms appear 6 to 7 weeks after infection Itching of the skin
  • 16. Who should be screened for Hepatitis C ? High-Risk Populations  People who inject drugs  Recipients of infected blood products or invasive procedures in health-care facilities with inadequate infection control practices  Children born to mothers infected with HCV  People with sexual partners who are HCV-infected  People with HIV infection  Prisoners/People who have had tattoos or piercings  Healthcare, emergency medical, and public safety workers after needle sticks, sharps, or mucosal exposures to HCV- infected blood;  Patients suffering from Thalassemia  Kidney disease patients receiving long-term hemodialysis  Unexplained long term liver disease and hepatitis including high liver enzymes
  • 17. What is thalessemia?  Thalassemia is an genetic blood disorder in which the body makes an abnormal form of hemoglobin  Hemoglobin is the protein molecule in red blood cells that carries oxygen  The disorder results in excessive destruction of red blood cells, which leads to anemia  Anemia is a condition in which your body doesn’t have enough normal, healthy red blood cells  These patients may need repeated blood transfusions and hence are prone to HCV infection
  • 18. What is hemodialysis ?  Hemodialysis is a treatment for kidney failure that uses a machine to filter blood outside the body  It is a process of purifying the blood of a person whose kidneys are not working normally  The blood travels through the tube to the filter, called a dialyzer  Inside the dialyzer, the blood flows through thin fibers that filter out  wastes  extra salt  extra fluid  After the dialyzer filters the blood, a different tube carries your blood back to the body  HCV infection may be common in these patients due to lack of standard infection control practices, physical proximity to an infected patient, and sharing of dialysis machines
  • 19. Disease Progression of HCV  Hepatitis C virus causes both acute and chronic infection  Acute HCV infection is defined as the presence of HCV within six months of exposure to HCV  Of every 100 people infected with the virus, about:  15–25 clear the virus without treatment (in the first six months after getting Hep C)  75–85 develop a long-term infection  70 develop chronic liver disease  10–20 develop cirrhosis (scarring of the liver) over a period of 20 to 30 years  1–5 will die of liver cirrhosis, or liver cancer
  • 20. How does HCV infection progress? Progression to cirrhosis may be increased by older age, obesity, immunosuppression, or consumption of excessive alcohol Hepatology. 2009;49:1335-74.
  • 21. •Mostly normal functioning of liver (Minimal impairment ) •Few or no symptoms •LFT normal •Abnormal functioning of liver •Symptoms present/ complications of cirrhosis seen •LFT abnormal How does liver status progress HCV infection?
  • 22. Diagnosis of HCV Screening test for HCV  Doctors use a blood test, called a Hepatitis C Antibody Test or Anti-HCV Test, to find out if a person has ever been infected with Hepatitis C  This test looks for antibodies to the Hepatitis C virus  Antibodies are chemicals released into the bloodstream when someone gets infected  Once people have been infected, they will always have antibodies in their blood even if they have been cured of the Hepatitis C virus
  • 23. Diagnosis of HCV A non-reactive or negative antibody test means that a person does not have Hepatitis C. However, if a person has been exposed to the Hepatitis C virus in the last 6 months, he or she will need to be tested again Reactive or Positive Hepatitis C Antibody Test means that Hepatitis C antibodies were found in the blood and a person has been infected with the Hepatitis C virus at some point in time
  • 24. Diagnosis of HCV  If the antibody test is reactive or positive, an additional blood test is needed to determine if a person is currently infected with Hepatitis C  This test is called a HCV RNA test : confirmatory test for HCV  This test cannot differentiate between acute and chronic infection HCV RNA test is negative HCV RNA test is positive Person does not have Hepatitis C Person currently has Hepatitis C Consult the doctor HCV antibody test positive
  • 25. Other tests Other blood tests If an initial blood test shows that you have hepatitis C, additional blood tests are:  Measure the quantity of the hepatitis C virus in the blood (viral load)  Identify the genotype of the virus: indicates the strain of the virus and is used in making decisions about treatment
  • 26. Other tests Tests for liver damage  transient elastography, a special ultrasound of the liver where a image of the liver can be seen on the screen to assess the extent of liver damage  liver biopsy, in which a doctor uses a needle to take a small piece of tissue from the liver which is examined under a microscope to look for liver damage Transient elastography Liver biopsy
  • 27. Treatment  The goal of treatment is to have no hepatitis C virus detected in your body at least 12 weeks after you complete treatment also called as cure  The cure rate depends on several factors including the genotype of the virus and the type of treatment given  The standard of care for hepatitis C is changing rapidly  Earlier weekly injections of interferons were administered with daily oral ribavirin (antiviral drug) for as long as 6-12 months  These medications cured only 40- 70% of patients depending on the HCV genotype  There remains a limited role for pegylated interferon and ribavirin with the entry of newer drugs called as directly acting antivirals (DAAs)
  • 28. Treatment : Directly acting antivirals  Directly acting antivirals : Sofosbuvir, daclatasvir , sofosbuvir-ledipasvir and sofosbuvir-velpatasvir fixed dose combination are part of the preferred regimens, and can achieve cure rates above 95%  Directly acting antivirals or DAAs and are much more effective, safer and better-tolerated than the older therapies  Therapy with DAAs can cure most persons with HCV infection and treatment is shorter (usually 12 weeks)  There is currently no vaccine to prevent hepatitis C
  • 29. END

Notes de l'éditeur

  1. building blocks of nucleic acids, nucleotides are composed of a nitrogenous base, a five-carbon sugar (ribose or deoxyribose), and at least one phosphate group.