Causes of Hepatitis:drugstoxinsalcoholviral infections (A, B, C, D, E)other infections (parasites, bacteria)physical damageWhat is hepatitis?
FunctionsStores sugar needed for energyAbsorbs good nutrientsBreaks down poisons (toxins) and drugsMakes important proteins that help build new tissue andrepair broken tissueProduces bile, which helps remove waste from the bodyLiver
Acute Hepatitis: Short-term hepatitis.Body’s immune system clears the virus from the bodywithin 6 monthsChronic Hepatitis: Long-term hepatitis.Infection lasts longer than 6 months because the body’simmune system cannot clear the virus from the bodyHepatitis Terms
Hepatitis B VirusCDC website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/hep_b/slide_1.htm
What is it?Hep B is a serious disease caused by a virus that infectsthe liverCan cause lifelong infection, cirrhosis (liverscarring), liver cancer, liver failure and deathHepatitis B
Family: HepadnaviridaeHepa: for liverDna: for Deoxyribonucleic acidVirion (aka Dane particle):Outer lipid envelopeIcosahedral nucleocapsid core composed of proteinOuter envelope proteins:Binding & entry into susceptible cellsSize: small, 42 nm in diameterStructure
Circular DNAUnusual, partially double strandedLong strand: 3020–3320 nucleotidesShort strand: 1700–2800 nucleotidesOne end of the long strand is linked to the viral DNApolymeraseGenome
Reverse transcription: one of the mRNAs is replicatedwith a reverse transcriptase making the DNA that willeventually be the core of the progeny virionRNA intermediate: HBV replicates through an RNAintermediate and produces and release antigenic decoyparticles.Integration: Some DNA integrates into host genomecausing carrier stateHBV: Replication
Clinical outcomes of Hepatitis BinfectionsFrom Murray et. al., Medical Microbiology 5th edition, 2005, Chapter 62, published by Mosby Philadelphia,,
Determinants or acute and chronic HBVinfectionFrom Murray et. al., MedicalMicrobiology 5thedition, 2005, Chapter66, published by MosbyPhiladelphia,,
Child-to-childContaminated needlesSexual contactsHealthcare workerBlood transfusion• 6% ofpeopleinfected overthe age of 5becomechronicallyinfectedPerinatal• 90% ofinfectedinfantsbecomechronicallyinfectedPerinatal transmission Horizontal transmissionTransmission of HBVCDC. Available at: http://www.cdc.gov/hepatitis. Accessed December 2006.Lee WM. N Engl J Med. 1997;337:1733-1745.Lavanchy D. J Viral Hepat. 2004;11:97-107.HostMotherInfantRecipient
Hepatitis B is NOT transmitted through food/water.Hepatitis B is NOT transmitted through casual contactsuch as hugging or shaking hands.Hepatitis B is NOT transmitted through kissing, sneezingor coughing.Hepatitis B is NOT transmitted through breastfeeding.What are some common myths andmisconceptions about Hepatitis B?
Hepatitis B acute infectionCDC website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/hep_b/slide_3.htmNote:Pattern ofserologicalmarkersvariesdependingonwhethertheinfection ifacute orchronic
Chronic Hepatitis B infectionhttp://www.cdc.gov/ncidod/diseases/hepatitis/slideset/hep_b/slide_4.htmNotes:In patients with chronicHBV infection, both HBsAgand IgG anti-HBc remainpersistentlydetectable, generally forlife. HBeAg is variablypresent in these patients.The presence of HBsAg for6 months or more isgenerally indicative ofchronic infection. Inaddition, a negative test forIgM anti-HBc together witha positive test for HBsAg ina single serum specimenusually indicates that anindividual has chronic HBVinfection.
Injection drug usersSex partners of those with Hep BSex with more than one partnerMen who have sex with menLiving with someone with chronic Hep BContact with bloodTransfusions, travel, dialysisWho is at highest risk?
Prevent perinatal HBV transmissionRoutine vaccination of all infantsVaccination of children in high-risk groupsVaccination of adolescentsVaccination of adults in high-risk groupsPrevention
Composition Recombinant HBsAgEfficacy 95% (Range, 80%-100%)Duration ofImmunity 20 years or moreSchedule 3 DosesBooster doses not routinely recommendedHepatitis B Vaccine
NauseaLoss of appetiteVomitingFatigueFeverDark urinePale stoolJaundiceStomach painSide painSymptomsA person may have all, some or none of these
FDA approvedInterferon AlfaLamivudine – reverse transcriptase inhibitorAdefovir – nucleotide analogue that inhibits viralpolymeraseInvestigationalTenofovir – adenine nucleotide analogueApproved for HIVEntecavir – guanosine analogue, highly selective for theHBV polymeraseTreatment options
1/3 of world’s populationhas been infected350 million with chronicdisease15-25% of these die due toliver related diseases1 million deaths annuallyUnited States1.25 million chronic carriers5000 deaths annuallyHepatitis B epidemiologyFigure 66-9. Worldwide prevalence of hepatitis Bcarriers and primary hepatocellular carcinoma.(Courtesy Centers for Disease Control andPrevention, Atlanta.)
Notes:HDV infection can be acquired either as a co-infection with HBV or as a superinfection of persons with chronic HBVinfection. Persons with HBV-HDV co-infection may have more severe acute disease and a higher risk of fulminanthepatitis (2%-20%) compared with those infected with HBV alone; however, chronic HBV infection appears to occurless frequently in persons with HBV-HDV co-infection. Chronic HBV carriers who acquire HDV superinfection usuallydevelop chronic HDV infection. In long-term studies of chronic HBV carriers with HDV superinfection, 70%-80%have developed evidence of chronic liver diseases with cirrhosis compared with 15%-30% of patients with chronicHBV infection alone.CDC website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/hep_d/slide_1.htm
Key features of Hepatitis Delta Virus•Single stranded, self complementary RNA,encapsidated in HbsAg•Small, amorphous particle•RNA encodes one protein: delta antigen•Replicates via RNA directed RNA synthesis,catalyzed by host RNA polymerase II
Key features of Hepatitis Delta Virus•Delta antigen required for replication, role unknown•Dependent on HBV as a “helper”•HBV provides HbsAg•May be acquired as co-infection with HBV, orsuperinfection of HBV infection•Exacerbates HBV induced disease
Hepatitis Delta VirionFrom Murray et. al., MedicalMicrobiology 5th edition, 2005,Chapter 66, published by MosbyPhiladelphia,,Figure 66-14
Consequences of hepatitis B and delta virus infectionFigure 66-15. Consequences of deltavirus infection. Deltavirus (d) requires the presence ofhepatitis B virus (HBV) infection. Superinfection of a person already infected with HBV(carrier) causes more rapid, severe progression than co-infection (shorter arrow).From Murray et. al., Medical Microbiology 5th edition, 2005, Chapter 66, published by Mosby Philadelphia.