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Hepatitis C virus (HCV)
Hepatitis C virus (HCV) infection is themost common chronic blood borneinfection in the United States;
approximately 3.2 million persons arechronically infected. Although HCV is notefficiently transmitted sexually, persons at
risk for infection through injection drug usemight seek care in STD treatmentfacilities, HIV counselling and testing
facilities.
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What is Hepatitis C Infection
Infection withHepatitis Ccauses
1 Chronichepatitis
2 Cirrhosis3 Hepatocellular
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HCV - Virology
Family Flaviviridae
Genus Hepacivirus
A small ( 50 nm )
virusss RNA virus,
positive senstive
RNA sequence
analysis into at leastsix major genotypes(Clades)
There are 100
subtypes.
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Why Hepatitis C is an importantDisease
WHO estimates 170 million ( 3 % ) worldpopulation is infected with HCV.Highest in Egypt.
Lowest in Sweden.In USA 2.7 to 3.4 million people infected.In USA there is a decline since 1990.Those born between 1940 and 1965 hadhighest incidence reaching a peak betweenthe age of 20 to 35 yearsIn USA 25,000 persons die of cirrhosis andchronic liver disease
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How Hepatitis C is transmitted
Bloodtransfusions
Drug absue Injections
Tattooing
Contamination ofMedicalequipment.
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HCVMother to Child transmission
Vertical transmissionoccurs in 3 -10%
Mother with higher
HCV viral loads or coinfection with HIVtransmit in higherrates.
No risk oftransmission isassociated withbreast feeding.
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Transmission of Infection inSpouses
Sexual transmission ofHCV can occur, withmuch lower frequencythan that of HIV, and HBVLong term partners ofHCV infected patientshave higher rates ofinfection than the generalpopulation.May be associated with
shared use of Razors andtooth brushes.
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CDC on Spouse Transmission
CDC on the basisof current evidence
does notrecommend use ofbarrier precautionsamong theheterosexualmonogamouscouples, to prevent
HCV transmission.4/22/2012 12
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Higher incidence of HCVInfections
Increased prevalencein
Sexuallytransmitteddiseases.
HIV co infection.Injecting druguse.
High risk sexualpractices.
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Health care devices and HCV
WHO calculates that unsafehealth care devices accountfor 2.3 million new HCVinfections per year, and200 000 HCV related
premature deaths, mostly inDeveloping countries
The re-use of injectionequipment's withoutsterilization contributes tomajor spread.
WHO estimates that about40% of injection relatedequipment is reused inDevloping countries.
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HCV and Blood Transfusions
Blood transfusionsfrom unscreeneddonors and unsafetherapeuticprocedures are majormodes oftransmission inDeveloping countries.
Paid donors are graverisk
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Trends of Change in
Transmission
Education among thedrug abusers, blooddonor screening needleexchange programmes
have remarkablyreduced the incidence.
Sexual, and Perinataltransmission has gained
importance.
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Needle Stick Injuries
A CDC report suggestedrisk of HCV transmissionis about six times higherper needle stick exposurethan is the risk with HIVinfection
( 1.8% vs0.35 )
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Onset of Infection in HCV
The average incubationperiod for HCV is 6-7days
The period for exposureto seroconversion is 8-9weeks.
About 90% of the infectedare anti HCV positive in 5months
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How Virus C replicates inHepatocytes
Depends on cellular factors and
shared by viral proteins.Replicates with viral and host
proteins
Multiplication rate is very high aTrillion particles are producedevery day.
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Pathology of HCV infection
Virus causes inflammation of Liver
Microscopically spotted parenchymal celldegeneration
Necrosis of Hepatocytes
Causes diffuse lobular inflammatory reaction
Disruption of liver cell cords
Accumulation of Macrophages neardegenerating Hepatocytes.
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Pathology
Both Hepatitis B and Care cytopathogenicCellular damage is
immune mediatedBoth HBV and HBC havesignificant roles in in thedevelopment ofHepatocellularcarcinomaCarcinoma may appear15 60 years after thebeginning of infection.
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Viral clearance from Hepatocytes
Virus clears either spontaneously or
by treatmentMay lead to cure, even fibrosis isregresses
Normalization of enzymes liverenzymes on clearance of virus
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Clinical course of Hepatitis CInfection
Acute HCV infection is asymptomatic
in most patients.
Natural history and chronicity ratevaries much between the populationgroups.
Persistence of virus has been definedas detectable HCV RNA for morethan 6 months from the time of
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Progress of HCV infections
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How Acute Infection Manifests
Symptomatic infection in only 15 % ofthe infected
Spontaneous clearance is higher inpatients present with symptomaticthan an asymptomatic acute HCVinfections
Major studies suggest that chronicityrates might depend on the mode ofinfection, and the age at which patient
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Acute manifestations
Only 10-20% of allacutely infected patientsdevelop Jaundice, Higher
incidence of Jaundice isin injecting drug users
Fatigue,myalgia,lowgrade fever.
Right upper quadrantpain,nausea or vomiting
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Other clinical Manifestations
Influenza likeillness
Dark colored urineClay colored stool
Jaundice is more
indicative ofdisease
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Progress of events in HCVInfection
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Bio Chemical marker
Concentration of Alanineaminotransferase greater than tentimes the upper limit of normal areuncommon.Even few cases symptomatic HCVinfection have reported increase up to20 timesThe presence of jaundice might be anindicator of an effective host immuneresponse, leads to spontaneous viralclearance.4/22/2012 29
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Diagnosis of HCV Infection
No definitive pathological test todiagnose acute HCV infection.
Diagnosis is supported by,
Identifiable exposure to HCV
Recent seroconversion
Marked increased concentration ofliver
enzymes
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Serology in Diagnosis
Detection of antibodies against HCVimmunoassay is unreliable to identify acuteinfectionsAntibodies may be absent in acute stageThe appearance of antibodies against HCVcould be delayed in as many as 30% ofpatients at the onset of symptoms,particularly in Immunosuppressed.IgMantibodies against HCV have not provenuseful in diagnosis of acute HCVinfections, as their concentration remainfairly constant in both acute and chronicinfections.4/22/2012 31
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RNA estimation in HCV
infections
HCV RNA levels couldfluctuate ( may beundetectable ) up to a
year after theinfection,necessitating serialmeasurements ofHCV RNA for a period
of 1 year.As many as 10% ofacutely infectedpatients might
eventually loseserological markers.4/22/2012 32
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Sensitive methods of Diagnosisof HCV infection
Qualitative andquantitative methodsof detection of HCVRNA by
1 Reversetranscriptase RT-PCR,
2 Branched DNA(bDNA)
3 Transcriptionmediated
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CDC guidelines for testing HCVinfection.
Testing for antibodies
Measuring Analineaminotransferase
concentrationTesting for HCV RNA by
PCR at 4 -6 weeks afterexposure and again forantibodies against HCV
and analineaminotransferaseconcentration at 4- 6months
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Prevention and Control
There is no vaccine for HCV infection
Control measures focus on
prevention activities that reduce risksfor contracting HCV
Major guidelines are
1 Screening and testingblood,plasma,organ, tissue,and
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Counseling and Educative
measures
Counseling ofpersons with highdrug or sexual
practicesImplementation ofinfection controlpractices in health
care and othersettings.
Professional and
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Treatment in HCV
Optimum timing of treatment is critical toavoid unnecessary treatment of those whowill clear the infection spontaneously
The evidence suggests that it is prudent towait for at least 12 weeks before initiatingantiviral treatment in patients with acuteHepatitis C, especially when they presentwith symptomatic hepatitis CPhysicians select the regimes dependingon the clinical experience and to suit thecircumstances.
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Treatment Regimen
With advent of newer pegylated
Interferons and use has improvedefficacy in patients with chronic HCVinfection, clinicians now use
pegylated interferon as first linetherpay,high sustained Virologicalresponse rates have been reported.
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N I t i HCV
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New Improvements in HCVTreatment
HCV treatment improved again in
2001 with FDA approval of pegylated
interferon. Attaching the polyethyleneglycol (PEG) molecule to interferon (aprocess called pegylation) keeps the
drug in the bloodstream longer andmakes it more effective against HCV.
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P l t d I t f
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Pegylated Interferonsreplaces
Replacing standard interferon withpegylated interferon has significantlyimproved response to HCV treatment and
requires a dosing regimen of only oneinjection per week . Currently, therapy withpegylated interferon plus ribavirin is the
standard treatment of HCV in HIV-positivepeople and the only FDA-approvedtreatment for coinfection.
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P i i i HCV
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Preventive strategies in HCVInfection
As there is no effective vaccine ,preventiveaspects should carry priority on
Universal screening of Blood and Bloodproducts
Sterilization of medical and dentalequipment.
Mandatory used of disposable needles,avoidance of unnecessary injections or
surgical procedures.Health workers, and public should beeducated about the risk of infection from
unsafe practices.Dr.T.V.Rao MD
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Created by Dr.T.V.Rao MDfor Medical and Health
Workers in the Developing
World