DR MONIKA RAJANI ASSOCIATE PROFESSOR DEPT OF MICROBIOLOGY CIMSH LKO INTRODUCTION Viral hepatitis refers to primary infection of liver caused by heterogenous group of hepatitis viruses which currently consist of ID: 917205
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HEPATITIS VIRUSES
DR MONIKA RAJANI
DR MONIKA RAJANI
ASSOCIATE PROFESSOR ,
DEPT OF MICROBIOLOGY
CIMSH ,LKO
Slide2INTRODUCTION
Viral hepatitis refers to primary infection of liver caused by heterogenous group of hepatitis viruses which currently consist of A,B,C,D,E and GOther hepatotropic viruses: herpes group :measles, rubella :adenovirus, YF, DV :Ebola virusDR MONIKA RAJANI
Slide3Viral hepatitis
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Slide4Classification
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Slide5Common features of hepatitis
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Slide6HEPATITIS A VIRUS
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Slide7HAV
First identified in 1973 by electron microscopyMost common cause of acute hepatitis in children in IndiaIn developing countries upward shift in age affectedAbout 1.4 million cases worldwideExtremely resistant to degradationDR MONIKA RAJANI
Slide8Morphology
Family picornavirusOriginally Enterovirus 72Genus: Hepatovirus27 nm ,SS nonenveloped RNA virusOne serotypeDR MONIKA RAJANI
Slide9Epidemiology
Natural infection in humans-Sporadics and outbreaksInfection acquired in childhood, asymptomaticBy age of 10 ,90%of population is immuneMOI: feco-oral-Food,water,milkHAV is contacted 100 times more frequently than cholera or typhoidYoung children have a key role in transmissionOutbreaks: Shell fish,raw oystersOvercrowding and poor sanitation,day care,summer campsOccasionally, HAV is also acquired through sexual contact (anal-oral) and blood transfusionDR MONIKA RAJANI
Slide10Pathogenesis and clinical features
I.P= 15-45 daysMultiplies in intestinal epithelial cellsInvades liver, shed in feces in late I.P and prodromeThe majority of infections are asymptomaticcomplete recoveryNo extra hepatic manifestations, no carrier state or chronicity and is not associated with cirrhosis or hepatocellular carcinomaInfection induces life long protectionFulminant hepatitis may occur in <1% of cases.DR MONIKA RAJANI
Slide11pathogenesis
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Slide13Lab diagnosis
LFTSample:feces or serumSerology: :ELISA-IgM anti HAV-acute infection -IgG anti HAV-PAST INFECTIONIEM: virus in fecesCell culture: hepatoma cell lines :Primary african green monkey kidney cell lines :Human fibroblastsMolecular tests: RT PCR :RFLPDR MONIKA RAJANI
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Slide15PREVENTION
Passive immunisation: :Pooled IgG given for pre and post exposure prophylaxis :Limited period of protection :ExpensiveActive immunisation: formalin inactivated vaccines :Grown in cell cultures :2 doses 6-12 months apart :HAVRIX,VAQTA,TWINRIX :Protection for 10 yearsTreatment:symptomaticDR MONIKA RAJANI
Slide16Hepatitis A vaccination is specifically recommended for:
-direct contact with someone who has hepatitis A.-Adults and children traveling to or working in countries with high or intermediate prevalence of hepatitis A, -Children and adolescents up to age 18 who live in states or communities where routine vaccination has been implemented because of high disease rates.-MSM-People using street drugs.-Anyone with an occupational risk for hepatitis A.-Persons with chronic liver disease, -People who are treated with clotting factor drugs.DR MONIKA RAJANI
Slide17HEPATITIS E VIRUS
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Slide18General features
Enterically transmitted NANB hepatitisCaused by non enveloped ss RNA virus belonging to Calciviridae familyGenus HepeviridaeDR MONIKA RAJANI
Slide19EPIDEMIOLOGY
Often occurs as epidemicsLargest epidemic appeared in Delhi in 1955-1956 affecting over 30,000 people within 6 weeksSewage contamination of city’s drinking water Kashmir, India (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991Feco oral transmission(contaminated water)Self liming illness, no chronicityDR MONIKA RAJANI
Slide20Zoonotic basis
Zoonotic transmission of HEV may be mainly via the consumption of uncooked or undercooked infected pork or game (wild boar, deer, or rabbit) meatrodents Direct contact with HEV-infected animals is another possible route of transmission of HEV DR MONIKA RAJANI
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Slide22HEV and pregnancy
In rare cases, acute hepatitis E can be severe, and results in fulminant hepatitis (acute liver failure); these patients are at risk of death. Fulminant hepatitis occurs more frequently when hepatitis E occurs during pregnancy. Pregnant women with hepatitis E, particularly those in the second or third trimester, are at an increased risk of acute liver failure, fetal loss and mortality. Case fatality rates as high as 20–25% have been reported among pregnant women in their third trimesterDR MONIKA RAJANI
Slide23Extrahepatic
manifestationsAcute pancreatitisGuillain-Barré syndrome Hemolytic anemia in people with the hereditary risk factor glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency)Glomerulonephritis with nephrotic syndrome and/or cryoglobulinemiaMixed cryoglobulinemia Severe thrombocytopenia DR MONIKA RAJANI
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Slide25Lab diagnosis
LFTIEMELISA(AB)PCRDR MONIKA RAJANI
Slide26HEPATITIS B VIRUS
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Slide27HBV: Introduction
Causative agent of Parenterally transmitted viral hepatitisMost widespread and most importantMore than one third of world population is infectedOne quarter of them are HBV carriers and one quarter of them develop chronic hepatitis, cirrhosis,and hepatocellular carcinoma.Hepatocellular carcinoma is the only human cancer that is vaccine preventable.It was discovered in 1965 by Blumberg and was earlier named as Australia AntigenDR MONIKA RAJANI
Slide28MORPHOLOGY
42 nm enveloped DNA virus Hepadnaviridae familyThree types of particles:Spherical-22nm-most abundant ,no nucleic acid- Filamentous-22nm -DR MONIKA RAJANI
Slide29Dane particle
: Complete hepatitis B particle: Double walled spherical particle: 42nm,few in no.DR MONIKA RAJANI
Slide30Structure of HBV-Dane particle
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Slide31Antigenic diversity
HBsAg -outer lipoprotein coat containing the surface antigen :Present both in hepatocytes and in circulationHBcAg –hepatitis B core antigen -NC protein :Present only in hepatocytes HBeAg – hepatitis B e antigen -NC protein :encodes for acute infection and replicationHBxAg- transactivating effects HB e AgDR MONIKA RAJANI
Slide32Viral genome
NC has two linear strands of DNA enclosed in circular configurationOne of DNA strands is incompletePartially double stranded DNADNA polymerase (+ strand) also presentDR MONIKA RAJANI
Slide33Viral genes
S gene:codes for surface antigenC gene:codes for core antigen :not secreted and does not circulate in blood :Detected only in hepatocytesP gene:codes for DNA polymeraseX gene:acta as transactivator for viral and cellular genesDR MONIKA RAJANI
Slide34S GENE
C GENEX GENEP GENEDR MONIKA RAJANI
Slide35Resistance
Susceptibility:Heat at 60 C for 10 hrsSodium hypochlorite2% glutaraldehyde5% formalin70% isopropyl alcoholDR MONIKA RAJANI
Slide36HBV :Epidemiology
Virus is maintained in a large pool of carriers HBV carrier: person with detectable HBsAg in blood for more than 6 monthsFollowing acute infection 10% of adults,30% of children and 90% of neonates become carriers450 million HBV carriers in world45 million HBV carriers in India Prevalance of hepatitis carriers in India is 2-7%Natural infection occurs only in humansNo animal reservoirSporadic infection or outbreaksDR MONIKA RAJANI
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Slide38Transmission
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Slide39Parenteral
transmision:Blood of carriers and less of patients is most important source of infectionBlood transfusion so screening of donors is strictly requiredArticles: shared syringes, needles,razors,nail clippers, endoscopes, combs ,razorsPractices: Acupuncture, tattooing,nose , ear piercing, circumcision ,field camps etcBody fluids: Semen,vaginal fluid, saliva, breast milk may also transmit infectionRisk groups: HCW, barbers, dentists, CSWYoung children: direct contact with open skin lesionsHBV IS 100 times more infectious than HIVDR MONIKA RAJANI
Slide40Perinatal
transmission:Congenital or vertical transmission in utero is rareInfection usually acquired during birth by contact with maternal blood with skin or mucosa of fetusInfection also acquired in immediate post natal periodBreast feeding to be avoidedRisk is high if mother is HBeAg positiveInfected neonates do not show clinical illness but remain carriers for lifeDR MONIKA RAJANI
Slide41ACTIVITIES
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Slide42Transmission of HBV
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Slide43Transmission
Sexual transmission:In promiscuous homosexualsHeterosexual contactArtificial insemination: semen donor screening is obligatoryDR MONIKA RAJANI
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Slide45Pathogenesis and clinical features
Incubation period:1-6 monthsInsiduous onsetExtrahepatic manifestations like MGN,PAN.may occur.DR MONIKA RAJANI
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Slide48Lab diagnosis
Liver Function Test – Total and direct bilirubin serum AST,ALT alkaline phosphatase PT total protein, albumin, globulin.Cannot grow in cell cultureDR MONIKA RAJANI
Slide49Lab diagnosis
Serology: ELISA1.HBsAg: :first marker to appear after infection(4 weeks) :Indicates presence of HBV infection : if persists for more than 6 months indicates chronicity 2. -Anti HBs: antibody to HBsAg: protective -indicates convalescence or vaccination3. Anti HBc (IgM or IgG)antibody to hepatitis B core antigen- -earliest AB marker to be seen in blood - First IgM then IgG -IgG Persists life long so useful indicator of prior infection4. HBeAg: high infectivity and active viral infection5. anti HBe: in convalescenceDR MONIKA RAJANI
Slide50Serological course
c
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Slide51Acute hepatitis B Chronic hepatitis B recent infection remote infectionHBsAg(<6 months), IgM antiHBc +HBeAg +viral DNA +followed by seroconversion to anti HBs and IgG antiHBc clearance of other markers90% of adults recoverHBsAg for more than 6 monthsPresence of IgG antiHBcAbsence of anti HBsSequelae:cirrhosis :hepatocellular carcinomaDR MONIKA RAJANI
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Slide53Molecular methods
:HBV DNA is an indicator of viral DNA replication and infectivityHelps to assess the progress of patients with chronic hepatitis under antiviral CT :Qualitative :conventional PCR :DNA DNA hybridisation :Quantitative: real time PCR :Branched DNA assay :Hybrid capture assay :typing:sequencing :RFLPDR MONIKA RAJANI
Slide54Prevention
General measures - screening of blood donors :use of sterile disposable syringes and needles :restriction of the number of sexual partners : careful handling of blood and blood products.Passive Immunization – Hepatitis B immunoglobin (HBIG) doses of 300-500 IU i.m. after accidental exposure : preferably within 48 hours.DR MONIKA RAJANI
Slide55Prevention
Active Immunisation 1:Plasma derived hepatitis B vaccine (Heptavax B, Merc & C) 2:Recombinant yeast derived hepatitis B vaccine (Engerix B) :absorbed with aluminium hydroxide :i.m. into deltoid region :3 doses given at 0, 1 and 6 months. 3:Recombinant DNA mammalian cell derived vaccine – GenHevac B (Pasteur, Merieux Connaught, 1993). 4:Combination vaccines Tetravalent DTP – HB vaccine Combined Hep A – Hepatitis B vaccine (Twinrix)DR MONIKA RAJANI
Slide56treatment
Acute hepatitis B:symptomatic treatmentChronic hepatitis B:1. Interferon (2a and2b)2. lamivudine 3. New agents – Ritonavir, Adefovir, Dipivoxil, Lobucavir, Famivir.Liver transplant:in ESLDDR MONIKA RAJANI
Slide57HEPATITIS C VIRUS
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Slide58HCV
Commonest cause of post transfusion hepatitis.Parenterally transmitted NANB hepatitis.Post transfusion NANB hepatitisDR MONIKA RAJANI
Slide59Hepatitis C virus(HCV)
Not been grown in culture but has been cloned in E coliFamily FlaviviridaeGenus: HepacivirusConsist of a core and envelopeEnvelope has glycoprotein spikesSingle stranded RNA genomeAntigenic and genetic diversity seenHighly mutable virusEscapes detection,elimination and immune surveillence by hostDR MONIKA RAJANI
Slide60Clinical features
Epidemiology, mode of infection and clinical disease resembles HBV200 million carriers12.5 million cases in indiaType C hepatitis is chronic illnessAbout 70-90% pts with acute HCV infection convert into chronic carriersCarrier state may lead to cirrhosis(40%) and carcinoma(10-30%)Main MOI is contact with infected blood or blood productsExtra hepatic manifestations seenDR MONIKA RAJANI
Slide61Course of events
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Slide62Extrahepatic manifestations
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Slide63Lab diagnosis
Liver Function TestSerology: ELISA :anti HCV is not specific :Does not differentiate between acute,chronic and past infectionImmunoblot assay: for confirmation Of ELISAMolecular: RT PCR TMA Branched DNA assay Molecular typing by:sequencing RFLP DR MONIKA RAJANI
Slide64Atypical forms of HCV
Normal aminotransferases levelsFluctuating AST/ALT levelsAsymptomaticAnti HCV AB negative or rise late in infection IgM does not correlate with HPE changesDR MONIKA RAJANI
Slide65TREATMENT
Acute hepatitis C:Pegylated interferon alphaChronic hepatitis C:IFN+ribavirinLiver transplant:in ESLDPREVENTIONGeneral measures as for HBVNo vaccine availableDR MONIKA RAJANI
Slide66HEPATITIS D VIRUS
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Slide67TYPE D HEPATITIS
HDV was discovered in 1977 in liver cells of patients infected with HBV.Also called as delta virus(genus)Defective RNA virus dependent on helper function of HBV for its replication and expression.No independent existence can survive and replicate as long as HBV infection persists in hostSS RNA genomeDR MONIKA RAJANI
Slide68Morphology
Spherical32nmOuter coat of HBsAgSs RNA genome carrying delta antigenDR MONIKA RAJANI
Slide69Clinical features
Mode of transmission is same as that of HBVTwo types of infection: 1: Co infection- :HDV and HBV are transmitted together at the same time. :clinically presents as acute hepatitis B infection 2:superinfection :delta infection occures in a person already harbouring HBV :leads to more serious and chronic infectionDR MONIKA RAJANI
Slide70Lab diagnosis
LFTSerology:IgM and IgG anti delta ABMolecular PCRImmunofluorescence:demonstration of delta antigen in liver cell nuclei.DR MONIKA RAJANI
Slide71prevention
Immunisation with HBV vaccine is effective as HDV cannot infect persons immune to HBV.DR MONIKA RAJANI
Slide72HGV
Discovered in 1995 in plasma of patients with chronic non A –E hepatitisRelated to HCV(flaviviridae)Blood transfusion most important mode of infection.Prevalance higher in HCV and HIV infected people.Mother to baby transmission also common.
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Slide73TTV
TTV, for transfusion transmitted virus or torque teno virus was first reported in a Japanese patient in 1997 it is often found in patients with liver diseaseIt is classified under the family Anelloviridae circular single-stranded piece of DNADR MONIKA RAJANI
Slide74Transfusion-transmitted infections
Viruses HBV, HCV, HDV and rarely (HAV, HEV) Cytomegalovirus (CMV), Epstein Barr virus (EBV)Human Herpes Viruses (HHV) 6 and 8HGV/GBV (GB virus) TTV and SEN-V.(HIV)Human T-cell Lymphotropic virusesParvovirus B19West Nile Virus Prions Parasites MalariaBabesiosisTrypanosomal infectionLeishmaniasisToxoplasmosisMicrofilariasis BacteriaBacterial ContaminationSyphilisDR MONIKA RAJANI
Slide75Comparison of hepatitis viruses
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Slide76Thank you
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