2. outline
• Definition
• Epidemiology
• Risk factors
• Modes of transmission
• Virology
• Pathophysiology
• Clinical features
• Diagnosis and screening
• Treatment
3. Definitions
• HCV-positive sense enveloped single stranded hepatotrophic virus of
flavivirus family and only member of hepacivirus
• Humans are the only hosts
• Previously referred as non A non B hepatic virus
• Higher mortality than that of HIV
4. Epidemiology
• Global incidence 2%
• 15% in Egypt and japan
• The most common indication for orthotopic liver transplantation
• Prevalence varies on age group- 1945-1965 born adults have high
seroprevalence
• One of the most common cause of chronic hepatitis
5. Transmission
1. Iv drug usage- 60 % incidence especially in the western community
and young HCV infected patients
cocaine, methamphetamine intranasal are risky
2. Blood transfusion- now eliminated but hemophiliacs are at increased
risk
-donor screening
-donation screening and
-donation deactivation significantly reduced blood related HCV
infection
6. 3. Chronic hemodialysis- 7% incidence in dialysis units
Difficult to control this route except serial patient screening
4. Nosocomial causes- contaminated and repeated usage of needles
and surgical utensils
5. Occupational hazards
Needle stick injury has 0.07-1.8 per chance
No need for prophylaxis
6. Sexual – highly inefficient – gays and commercial sex worker and STI
infected individuals are at increased risk
7. 7. Vertical transmission
Most of childhood infection in developing countries is due to MTC
transmission.
2-8% incidence
Increased risk with –high maternal viral load
- HIV coinfection
- vaginal delivery
HCV treatment is contraindicated during pregnancy, child remains anti HCV
+ve for 12 months dueto placental Ab transfer
Infant to be tested with PCR at 2 occasions or post 12 months Anti HCV
status
• Maternal routine screening and test in not recommended as nothing much
will be given to decrease the transmission rate as treatments are
contraindicated
8. Genetics
• Positive sense RNA—transcribed in to polyprotein
• Polyprotein has structural- E1, E2 and core proteins
• P7
• Non structural proteins with enzymatic activity
• Viral particles are not found integrated in host cell and are secreted
enveloped with VLDL, LDL and chylomicrons
• Envelope protein shows hyper variability
• Quasispecies-closely related but distinct particles
• Six genotypes= 1,2,3 are western, 4middle east, 5 south Africa and 6 far
east
• Genotype 1 is associated with low SVR and commonest type
9. pathophysiology
• Hepatocytes are primarily infected by HCV, other cells are indicated as a
reservoirs in relapse after SVR achievement
• No direct cytopathic effect is proven
• Most clinical features are due to immune responses
• SVR= sustained virologic response defined as negative HCV
RNA/undetectable after 12 to 24 months of viral suppression therapy
• Clearance of the virus is associated with robust and coordinated innate and
adaptive immune response.
• Cytopathic effect is indicated in AIDS, organ recipients and
immunocompromised individuals as acute progressive fibrosing cholestatic
hepatatis
10. Innate immunity
• Innate immunity identifies the PAMP molecules using TLR and
initiates translation of INF beta that inturn activates INF inducible
genes and INF alpha production
• INF inhibit viral replication and initiates apoptosis of infeted
hepatocytes
• HCV NS5 deactivates TLR associated immune response to evade host
response
• NK are essential for clearance of HCV infection
11. Adaptive immunity
• Adaptive immunity is not sufficient to effectively clear HCV infection
• Production of Anti HCV is not associated with high likely of HCV
clearance
• Robust CD4 and CD8 cellular response is associated with infection
resolution
• HCV evades adaptive immunity by:
High antigenic variability
Envelope shielding with LDL, VLDL and Chylomicrons
Quasispecies nature
Syncytia formation and direct cell to cell viral transmission
12. Histopathologic features
• Paucity of inflammation
• Portal lymphocytosis with germinal follicles
• Interface hepatitis and piecemeal necrosis
• Hepatic steatosis
13. Clinical features
• Acute HCV- majority are asymptomatic
• Fatigue
• Anorexia
• Nausea and vomiting
• RUQ pain
• Arthralgia
• Myalgia
• Rarely icterus
14. Spontaneous clearance vs chronicity
• 85% chance of chronicity
• Genetics seems to decide the fate
• Young icteric women with severe acute HCV manifestations have low
chance of chronic progression
• HIV, concomitant liver disease, alcoholism and old age, non icteric
acute phase are associated with chronicity
15. Chronic HCV
• Fatigue – most common
• Anorexia
• Weight loss
• Arthralgia
• RUQ pain
• Advanced- portal HTN, ascites and coagulopathy, peripheral stigmata
• Few with extra hepatic cutaneous, renal and endocrine
manifestations
16. • Majority of chronic HCV infected patients are compensated and
asymptomatic
• Flares of hepatitis are common
• Few has minimal periportal and some bridging fibrosis
• Only 25% progress to cirrhosis
• 1-4% HCC
• Liver fibrosis staging is the only prognostic marker
17. Factors determining hepatocytic deterioration
• Duration of HCV infection
• Histologic grading and staging
• Hepatic iron load
• HIV coinfection
• Alcoholism, steatosis, autoimmune hepatitis, HBV, drug induced..
• Obesity
• Quasispecies diversity
• Older age
18. diagnosis
• Anti HCV IG- 99% sensitivity by EIA
• Can not differentiate between chronic and resolved infection
• False +ve=infants born from anti HCV +ve mothers
• False –ve= immunosuppressed
AIDS
organ recipients
chronic dialysis patients
19. Immunoblotting and NAT
• RIBA- confirmation
• NAT- the most sensitive and specific test
Qualitative (very sensitive to viral RNA) vs quantitative
Can differentiate acute vs chronic
Helps to determine treatment progression
For confirmation in false +ve individuals
Genotyping is vital for treatment selection
20. miscellaneous
• LFT- moderate and intermittent ALT fluctuations
albumin <5mg in decompensated and mild and fluctuating
hyperbilirubinemia
• CBC- anemia and treatment induced cytopenia monitoring
do CBC every 2wks for the first 8 weeks then once monthly after
initiation of treatment
RFT GFR<50 is contraindication for treatment
ESR- elevated
U/A
ANA, APLA, LKM-1
Imaging U/S, MRI, endoscopy, CT
21. screening
• Screening is using anti HCV/PCR recommended for the following high
risk groups
1. HIV infected
2. Childs of HCV infected mother
3. IV drug users
4. Blood donation recipients
5. Dialysis unit patients
6. Organ transplant recipients
7. Health care professional with accidental exposure
8. Unexplained ALT, essential mixed cryoglobulinemia
22. DDX
• Viral hepatitis- HBV, HDV, HBV/HDV do HBsAg, HBcAg, HBeAg, anti HDV
• Autoimmune differentiate from Type 2 AIH by LKM1 titer and Anti HCV
value
• Drug induced
• Other non specific viral infections
• Hemochromatosis- total body iron overload- biopsy the liver
• Alcoholic- high AST value
• Metabolic
• Ideopathic
• Malignancy- imaging+ biopsy
24. Extra hepatic manifestations
• Autoimmune- anti LKM1, ANA associated hepatitis
• Essential mixed cryoglobulinemia- can be type 2 with monoclonal
IgM+ polyclonal IgG or type 3 with polyclonal IgM+ IgG
• C/F
Systemic cutaneous vasculitis- rash
Arthralgia
MPGN type 2
Porphyria cutanae tarda
25. continued
• Endocrine- type 2 DM and variable insulin resistance
autoimmune thyroiditis
sjogren syndrome
Skin – vasculitis and lichen planus
Myeloproliferation- B cell non Hodgkin’s marginal cell lymphoma
26. complications
• Rare- fulminant hepatic failure
• Acute fibrosing cholestatic hepatitis
• Cirrhosis
• Portal HTN, Variceal bleeding, Coagulopathy, Ascites, encephalopathy
• HCC- 20 to 30 years after cirrhosis
