This presentation was presented at Burdwan Medical College, Burdwan.

1. HEPATITIS C
AYAN SANTRA

2. • It is the inflammation of liver caused by
Hepatitis C virus.
• It is the most common cause of non A non B
hepatitis.
• It is a major cause of chronic liver disease in
the world.

3. Hepatitis C virus
• Part of Flaviviridae family of viruses
– Associated with both human and animal disease
– 3 genera: pestiviruses (cattle, pigs), flaviviruses
(dengue, yellow fever), hepaciviruses (HCV)
• It is an enveloped, icosahedral virus having single
stranded positive sense RNA.
• 6 genotypes worldwide, many subtypes and
isolates based on nucleotide diversity
• Quasispecies within individual
• In vivo replication in liver and lymphocytes

5. HCV Genome
• 9.6 kb positive strand RNA genome
• Open reading frame encoding polyprotein of
~3010 amino acids
• 3 highly conserved areas:
–5’ UTR: initiating translation
–Core: codes for capsid protein monomer
–3’ UTR: essential for RNA synthesis &
packaging

7. Life cycle

8. Mode of Transmission
6015
10
4 11
Injecting drug use
Sexual trnsmission
Transfusion before
screening
Occupational
Others
Incubation period: 2 to 26 weeks; Mean 6-12
weeks

9. Immune response
• Patterns of viraemia
1. Drop after peak  successful control
2. Drop followed by rebound  chronic
infection
3. Consistent HCV  chronic infection

10. Innate immune response

11. Viral resistance
• NS 5A & E2 can interfere with PKR
• The core protein can inhibit the JAK-STAT
pathway by which IFN signals
• NS3/4A can block the accumulation of
phosphorylated IRF3 which inhibitrs
expression of type 1 interferons and IFN
stimulated genes.

12. Cell mediated immunity
• More vigorous CD8+ and CD4+ T cell
responses in all individuals that controlled
infection
• Chronic infections occur when
–unable to mount HCV-specific T cell
responses
–strong response that results in viral RNA
clearance, followed by contraction in
CD8+/CD4+ and rebound in viremia

13. Antibodies
• Role of antibodies unclear and poorly studied
• Virus can be cleared in absence of detectable
antibody responses
• Neutralizing antibodies target E2, which is
highly variable and able to evade

14. Immune-mediated liver injury
• Host immune response and not viral
replication
• HCV infects only 1-10% of hepatocytes
• IFN-γ and TNF-α from CD8+ destroy nearby
non-infected hepatocytes (“bystander killing”)
• HCC occurs mainly
due to high turnover
rate in hepatocytes

15. Clinical features
Acute
• Usually
asymptomatic
• Constitutional
symptoms
• Jaundice
• Right upper quadrant
pain
Chronic
• When there is persistent
RNA for more than 6
months
• Fatigue is the most
common symptom
• Jaundice is rare
• Immune complex
mediated diseases

16. Immune complex mediated diseases
• Essential mixed cryoglobulinaemia
• Membranoproliferative glomerulonephritis
• B cell lymphoma
• Unexplained monoclonal gamopathy
• Extrahepatic complications unrelated to
immune complexc:Sjogren syndrome,Lichen
planus, Type 2 diabetes melitus

17. Course

18. Patients with risk to progression to
chronic hepatitis
• Older age
• Longer duration of
infection
• Advanced histologic
stage and grade
• Genotype 1
• More complex
quasispecies variety
• Increased hepatic iron
• Concominant other liver
disease
Alcoholic liver disease
Hemochromatosis
α₁ antitrypsin deficiency
Steatohepatitis
• HIV Infection
• Obesity

19. Diagnosis
Liver function test
Parameters Acute Chronic
Bilirubin (both conj
& unconj)
Raised Raised
ALT/AST Increased (400-1000
IU/L)
Episodic rise
Alkaline
phosphatase
Normal to ˂3 times
normal elevation
Normal to ˂3 times
normal elevation
Albumin Normal Decreased
Prothrombin time Usually normal Increased

20. Anti HCV antibody
First
generation
Against C100-
3 (NS4)
Appear 1-3
weeks after
infection
Second
generation
Against C200
& C33c (NS3)
Appear 9-10
weeks After
infection
Third
generation
Against C22-3
(core) & NS5
Appear 7-9
weeks after
infection

23. HCV RNA
• In acute infection detected within 2 weeks.
• Decreases after antibody production.
• Detected by
1. PCR
2. Branched DNA technique.
• HCV antigen: an EIA for hcv antigen is
available but less sensitive than HCV RNA.

24. Prognostic test
• 1.Genotyping:
Detected by : DNA sequencing, PCR
hybridization
Genotype 1&4 have worst prognosis.
Genotype 2&3 have better prognosis.
• 2. Viral load: high viral load→ poor response
to therapy.

25. Liver biopsy
• It is done in chronic hepatitis
To know the etiology ,
For grading and staging of the disease
To monitor the treatment.

26. Liver biopsy finding in
chronic hepatitis C
• 1.Portal tracts: Inflammation may confine to portal
tracts or may spill into adjacent parenchyma, with
necrosis of hepatocytes (interface hepatitis);there may
be bridging inflammation and necrosis. The portal
infiltrate is rich in lymphocytes, often forming
lymphoid aggregates and even a follicle with prominent
germinal centres.
• 2. Bile duct lesion: swelling and polystratifications of
bile duct lining cell, infiltration by lymphocytes and
larger macrophages and preservation of the basement
membrane of the bile duct.

27. Liver biopsy finding in
chronic hepatitis C
• 3. Lobular lesion:
• There may be loss of architecture. Hepatocytes show
balloning degeneration and necrosis.There may be
bridging necrosis.
 May comprise a striking number of acidophil bodies
 Cholestasis may be there.(canalicular bile plugs)
 Mild to moderate steatosis, usually macrovesicular
type( more common in genotype 3).
 Increased amount of hepatic iron even in absence of
blood transfusion.

28. Liver biopsy finding in
chronic hepatitis C
 Periportal hepatocytes may contain Mallory Denk body
like coarse clumps of eosinophilic cytoplasm.
 The lymphocytic infiltration in the lobules form rows
along the sinusoids.
 Fibrosis is progressive in chronic hepatitis C. Portal
deposition→ Portal and periportal deposition→
Formation of bridging fibrous septa.
 Angiogenesis occurs in CHC in the portal tract, fibrous
septa and periportal zone.
 Continued loss of hepatocytes and fibrosis results in
cirrhosis,with fibrous septae and hepatocyte
regenerative nodule.
HCV RNA can be detected by in-situ hybridization.

30. Chronic hepatitis C
showing portal tract expansion with inflammatory cells and fibrous tissue and
interface hepatitis with spillover of inflammation into the adjacent parenchyma. A
lymphoid aggregate is present.

31. Scheuer system of grading and staging
Grading
Grade 1 no or minimal
inflammation
Grade 2 Portal inflammation or
lobular inflammation,
no necrosis.
Grade 3 Mild piecemeal
necrosis or focal
hepatocellular necrosis.
Grade 4 Moderate piecemeal
necrosis or severe focal
damage.
Grade 5 Severe piecemeal
necrosis or bridging
necrosis.
Staging
Stage 0 No fibrosis.
Stage 1 Enlarged fibrotic
portal tract.
Stage 2 Periportal or
occasional portal
to portal septa.
Stage 3 Bridging necrosis
with
architectural
distortion, no
obvious
cirrhosis.
Stage 4 cirrhosis

33. Prevention
• Never share drug equipments
• Practice safer sex
• Always use new sterilized
equipments
• Don’t touch dirty needles