Hepatitis C Virus Non A, non B Hepaci virus
What is Hepatitis C Virus Hepatitis C virus also known as Non A or Non
B virus found while doing experiments on Chimpanzees. HCV infections are seen only in humans The epidemiology is like HBV infection.
HCV Virology
Hepatitis C Virus capsid envelope protein
protease/helicase
c22
33c
RNA- RNA polymerase dependent
c-100
’5
’3 cor E1 e
E2
hypervariable region
NS 2
NS 3
NS 4
NS 5
Hepatitis C virus Genotype 1 and 4 has a poorer prognosis and response to interferon therapy, In Egypt, the prevalence is about 1216% Now 6 genotypes are identified.
Pathogenesis
Hepatitis C - Clinical Features Incubation period:
Average 6-7 wks Range 2-26 wks
Clinical illness (jaundice):
30-40% (20-30%)
Chronic hepatitis:
70%
Persistent infection:
85-100%
Immunity:
No protective antibody response identified
How HCV transmitted Blood transfusions Transplantation of organs Injectable drug abusers Immunocompromised Sexual transmission ?
Less important Vertical transmission is possible
Clinical features About 50 – 80% patients progress to chronic
hepatitis May progress to Cirrhosis, or Hepatocellular carcinoma
Chronic Hepatitis C Infection  The spectrum of chronic hepatitis C infection is
essentially the same as chronic hepatitis B infection.  All the manifestations of chronic hepatitis B
infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.
Transmission of HCV Percutaneous IV drugs Clotting factors before viral inactivation Transfusion, transplant from infected donor Therapeutic (contaminated equipment, unsafe injection practices) Occupational (needle stick) Per mucosal Perinatal Sexual
Risk Factors Associated with Transmission of HCV Transfusion or transplant from infected donor Injecting drug use Hemodialysis (yrs on treatment) Accidental injuries with needles/sharps Sexual/household exposure to anti-HCV-positive contact Multiple sex partners
Hepatitis C Virus Infection Typical Serologic Course antiHCV
Symptoms
Titre
ALT
Normal 0
1
2
3 4 5 Months
6
1
2
3 4 Years
Time after Exposure
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Laboratory Diagnosis  HCV antibody - generally used to diagnose
hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.
 ELISA test results to be confirmed with
Immunoblotting assay ( EIA, RIBA)
RIBA OR EIA
PCR
Molecular Methods in Diagnosis  HCV-RNA - various techniques are available e.g.
PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.
Prognostic Tests Genotyping – genotype 1 and 4 have a worse
prognosis overall and respond poorly to interferon therapy. A number of commercial and in-house assays are available. Viral Load – patients with high viral load are
thought to have a poorer prognosis. Viral load is also used for monitoring response to IFN therapy.
Treatment Interferon - may be considered for patients
with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment. (Peg IFN) Ribavirin Studies suggest that a combination
of interferon and ribavirin is more effective than interferon alone.
Thyroid dysfunction
Prevention of Hepatitis C Screening of blood, organ, tissue donors High-risk behavior modification Blood and body fluid precautions
Assessment of therapy: response and Efficacy Several tests are used to assess therapy in HCV infection. These include • Biochemical markers (ALT) • Histologic markers • Clinical progression and mortality, • Viral load (HCV RNA). • SVR: defined as the absence of HCV RNA from serum 24 weeks after discontinuation of therapy. This response is generally considered to be a virological cure.
Additional significant markers include (a) End of treatment response, defined as undetectable virus at the end of a 24- or 48week course of (b) Rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of (c) early virological response (EVR), defined as a more than 2-log reduction or complete absence of serum HCV RNA at week 12 of therapy compared with baseline.
Failure (a) Non-responder, defined as no reduction in HCV RNA during treatment; (b) Partial responder, defined as reduced HCV RNA during treatment and increased HCV RNA after treatment period; and (c) Relapse, defined as HCV RNA undetectable during treatment followed by high HCV RNA at the end of therapy