Hepatitis c

2. PRESENTED BY:
Dr. Nivedita Yadav
Dr. Parul Singhal
Dr. Kanishka Tyagi
MDS-2023
Dept. of OMFS

4.  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)

5.  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.

6.  Virology of HCV:
 Structure:
 HCV is 55-66nm in size
 Enveloped (means it have lipid envelop)
 Single strand RNA virus
 Family – Flaviviridae so called as Flavi virus
 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.

15. Natural history of HCV

17. • Liver fibrosis results from chronic damage to the liver
in conjunction with the accumulation of ECM
proteins(collagen , fibronectin , tenascins , lamnins ,
proteoglycans etc ), which is a characteristic of most
types of chronic liver diseases .
• The main causes of liver fibrosis include chronic HCV
infection, alcohol abuse, and nonalcoholic
steatohepatitis (NASH).

18. • The accumulation of ECM proteins distorts the hepatic
architecture by forming a fibrous scar, and the
subsequent development of nodules of regenerating
hepatocytes defines cirrhosis.
• Cirrhosis produces hepatocellular dysfunction and
increased intrahepatic resistance to blood flow, which
result in hepatic insufficiency and portal hypertension,
respectively.

19.  Factors increasing the rate of HCV disease
progression:
 Age increased progression increased.
 In Males it is more rapid than in females.
 Alcohol consumption.
 HIV co-infection.
 Fatty liver.

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

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

22.  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.
 Around 30% (15–45%) of infected persons
spontaneously clear the virus within 6 months of
infection without any treatment. ”spontaneous virus
clearance” (HCV RNA clear).
 Remaining 70% develop chronic hepatitis.

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

24. • Blood testing
1. Serological
test – to test
Anti-HCV
antibodies
2. Hepatitis C PCR
test to find virus
in blood
• Liver function tests
HOW IS HEPATITIS C
DIAGNOSED?

25. anti-HCV
antibodies
nucleic
acid test
This test is important because about 30% of people
infected with HCV spontaneously clear the infection
by a strong immune response without the need for
treatment. Although no longer infected, they will still
test positive for anti-HCV antibodies.
If positive

26.  Normal AST, ALT, PT & albumin become abnormal if
cirrhosis is developed
 Liver biopsy is the best test to determine the amount of
inflammation and liver fibrosis
 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.

27.  Seroreversion: means patients who have not yet
developed antibodies.
 All HCV nucleic acid tests PCR & TMA - transcription-
mediated amplification 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)
.

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

29. 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. It should be <1

30.  ALP “ Alkaline phosphatase”
 Total 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.

31. Liver biopsy

32. 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).

33.  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.
 PEGylation changes the uptake, distribution, and
excretion of interferon, prolonging its half life time.

34.  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.

35.  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.

36. Who should be treated?

37.  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.

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

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

42. 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