Hepatitis c infection, causes, treatment, and prevention.

3.  History :
 The first recognition of cases that caused neither
by hepatitis A virus nor hepatitis B virus came in
1975.
 This form of disease was called non –A-non –B
hepatitis virus.
 In 1989 this virus was identified, cloned and
named hepatitis C virus (HCV)

4.  Of those exposed to HCV, about 40% fully recovered
because of their immune system that able to fight off the
virus naturally.
 The remainder whether they have symptoms or not,
become chronic carriers.
 Of these carriers, 20% develop cirrhosis and of those with
cirrhosis, up to 20% develop liver cancer.

5.  Egypt has the largest epidemic of hepatitis C virus(HCV)
in the world.
 Over 11000 individuals were tested and overall
prevalence of people positive for HCV antibody was
14.7%.
 In Egypt, the major route of exposure:
 Using injection therapy.
 Inadequate infection control practice.
 History of anti-schistosomal injection treatment.
 Using glass syringes.
 Dentistry.

7.  Virology of HCV:
 Structure:
 HCV is small(55-66nm) enveloped positive single strand
RNA in the family Flaviviridae.
 The core of genetic material(RNA) is surrounded by a
protective shell of protein, encased in a lipid envelop of
cellular origin.
 Two viral glycoprotein, E1&E2 are embedded in the lipid
envelope.

9.  Genome :

11.  Genotype :
 HCV classified into 6 genotypes, several subtypes and
species.
 1,4 are less responsive to interferon-based treatment
than other genotypes 2,3,5,6.
 Duration of interferon-based therapy:
1,4 48 weeks
2,3 24 weeks
 Infection with one genotype not confers immunity
against others, infection may possible with two strains.

16. Natural history of HCV

18.  Factors increasing the rate of HCV disease
progression:
 Age increased progression increased.
 Male is more rapid than female.
 Alcohols consumption.
 HIV co-infection.
 Fatty liver.

19.  Symptoms :
 Joints pains.
 Sleep disturbance.
 Nausea.
 Depression.
 Fatigue.
 Flue-like symptoms.

20.  Acute:
Refers to the first months after infection, between 60-70% of
people infected develop no symptoms during the acute
phase.
 Symptoms :
 Decrease appetite.
 Fatigue.
 Abdominal pains.
 Itching.
 Fatigue
 Jaundice.
 Flue-like symptoms.

21.  HCV detected in blood of infected person within 1 to 3
weeks of infection by PCR and antibodies of virus are
detected within 3- 15 weeks.
 4-15% clear virus during the acute phase ”spontaneous
virus clearance” (HCV RNA clear).
 Remaining 60-85% develop chronic hepatitis.

22.  Chronic :
When infection persisting for more than 6 months(
asymptomatic).
 Symptoms of cirrhosis:
 Ascites “ accumulation of fluids in the abdomen”.
 Bruising and bleeding tendency, enlarged veins,
especially in stomach and esophagus.
 Jaundice and a syndrome of cognitive impairment.
 Hepatic encephalopathy due to the accumulation of
ammonia and other substances normally cleared by
healthy liver.

23. • Blood testing
1. Hepatitis C
antibody test
2. Hepatitis C PCR
test to find virus
in blood
• Liver function tests
HOW IS HEPATITIS C
DIAGNOSED?

24.  Normal AST, ALT, PT & albumin become abnormal if
cirrhosis is developed
 Liver biopsy is the best test to determine the amount of
inflammation.
 Serological blood tests used to detect antibodies of HCV.
 HCV antibodies can be detected in 80% of patients within
15 weeks of exposure, in 90% within 5 months of
exposure and in >97% within 6 months after exposure.

25.  Seroreversion: means patients who have not yet
developed antibodies.
 All HCV nucleic acid tests (PCR&TMA) have the capacity
to detect not only whether the virus is present but also to
measure the amount of virus present in blood(viral load)
 Important factor in determining the probability of
response to interferon-based therapy but neither indicate
disease severity nor the likelihood of disease progression.

26.  In patient with confirmed HCV infection, genotype testing
1 generally recommended.
 HCV genotype testing is used to determine the required
length and potential response to interferon-based
therapy.

27. HCV Diagnostic tests
 Liver function tests :
 ALT “ Alanine transferase”
GPT “ glutamic pyruvate transaminase”
 AST “ Aspartate transaminase”
GOT “ Glutamate oxaloacetic transferase”
Ratio of AST to ALT used to differentiate between causes of
liver damage.

28.  ALP “ Alkaline phosphatase”
 Total bilirubin
 Bilirubin if increase, it cause jaundice and cause:
 Pre hepatic: hemolytic anemia, internal hemorrhage.
 Hepatic : problem with the liver, reflected as deficiencies
in bilirubin metabolism(reduced hepatocyte uptake and
secretion of bilirubin), cirrhosis and hepatic virus.
 Post hepatic: obstruction of the bile ducts, reflected as
deficiencies in bilirubin excretion.

29.  Gamma glutamyl transferase “ GT”
 Enzyme-linked immunosorbent assay(ELISA):
I. Sandwich assay:

31. II. Competitive binding assay:
 Used when a matched
pair of antibodies to the
analytes doesn’t exist.
 Ab+ fixed amount of
labeled ligand+ variable
amount of un labeled
ligands incubate.
 When conc. Of unlabeled
increase, labeled ligand
can bind to the antibody
and the measured
response decrease, lower
the signal.

33.  Antigen-down immunoassay
“immunometric assay “

34.  TMA( transcription mediated amplification):

36.  Advantage of TMA:
 Specificity ~ 99.5%.
 Easy sample preparation.
 Inherent design prevents contamination.
 Efficient cost effective technology(high throughout 100
specimen/5hrs).

38. Liver biopsy

39. Treatment
 Alpha interferon: is a host protein that is made in
response to viral infection and has antiviral activity.
 Another recombinant forms have been produced (alfa a2,
alfa b2, consensus interferon).

40.  Peginterferon: is an alfa interferon that is chemically
modified by the addition of a large inert molecule of
polyethylene glycol.
 It is used instead of alfa interferon forms, which are
mentioned in the previous slide.
 Pegelation changes the uptake, distribution, and
excretion of interferon, prolonging its half life time.

41.  Ribavirin:
 An oral antiviral agent that has activity
against a broad range of viruses.
 It has little effect on HCV, but adding it to interferon
increases the sustained response rate by 2-3 folds.

42.  Combination therapy leads to:
 Rapid improvement in serum ALT levels.
 Disappearance of detectable HCV RNA in up to 70% of
patients.
 A response is considered “sustained” if HCV RNA remains
undetected for 6 months or more after stopping therapy.

43. Who should be treated?

44.  Patients with HCV, HCV RNA , elevated
serum aminotransferase.
 evidence of chronic hepatitis on liver
biopsy with no contraindications
should offered combination therapy.
 Patients with chronic HCV according to
response to antiviral therapy.
 Patients with cirrhosis if they don’t
have signs of decompensations such as
ascites, persistent jaundice or hepatic
encephalopathy.

45. High rates Low rates
• Women
• Youth
• Normal weight patients
• Patients with lesser degree of
fibrosis on liver biopsy
 Men
 Old
 Over weight patients

46. Who should not be treated?
 Contraindications to peginterferon therapy include:
 Severe depression
 Alcohol abuse
 Auto immune disease
 Bone marrow transplantation
 Marked anemia

48. New and future treatments:
 Drug affecting the immune
response against the virus
 Known as immune modifiers or
immunomodulators.
 Alters the inflammatory response
against liver cells infected with the
virus.
 Compounds of this type currently
being tested in humans include:
 Thymosin alpha1
 dihydrocholoride

49.  Specific agents against HCV
proteins
 One target for such drugs is HCV
RNA genome.
 Ribozyme (hepatazyme) can be
designed to cleave HCV RNA
genome in a region that the virus
needs to survive.

50.  Drugs that affect liver’s response
to injury
 Chronic HCV can lead to fibrosis
and cirrhosis.
 IP-501 (interneuron
pharmaceuticals) is an orally
administrated antifibrotic drug
tested for treatment of alcoholic
and HCV induced cirrhosis.

51.  Re-grow a damaged liver
 When liver is damaged
beyond repair, the only hope
is liver transplantation.
 Liver stem cells can be
isolated and grown into
hepatocytes and bile duct
cells in the laboratory.

52. Created by: Nada Sami, BSc in Microbiology &
Chemistry and a postgraduate student.
E-mail: nada_m78@yahoo.com