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1、Hepatitis Viruses 2024/8/21HepatitisinflammationoftheliverMainlycausedbyagroupofvirusesHepatitisA,B,C,D,EUsuallytheirinfectionsareasymptomatic,butdisplaysimilarclinicalfeatures,nausea,vomiting,raisedliverenzymes,jaundice2024/8/2Hepatitis viruses2Hepatitis Viruses 2024/8/232024/8/2中华流行病学杂志2015,Vol.36
2、Issue(2):144-147IncidenceofnotifiedcasesofviralhepatitisinChina,2003-20134Hepatitis A virusFeinstone19732024/8/25Biological Properties Picornaviridae, genus Hepatovirus Icosahedral particle Non-enveloped, resistant to acidic pH +ss RNA genome Single serotype worldwide 2024/8/26ResistanceStable to:ac
3、id at pH 1detergentstemperature 4: weeks; 56for 30minutes: stable 60for 20minutes : partial inactivation saltwater, groundwater: several months2024/8/27PathogenesisSource of infection: patient, inapparent infectionTransmit: fecal-oral route contaminated water, in food, and by dirty hands *Shellfish(
4、 clams (蛤), oysters (蛎), and mussels（蚌） ) Shellfish can concentrate the viral particles 300,000peoplewereinfectedwiththevirusastheresultofeatingHAVcontaminated-clamsinShanghai,Chinain1988,2024/8/28PathogenesisFecal-oralrouteSymptomsrelatedtoimmuneresponseandnotdirectcytopathiceffectofvirus.Asymptoma
5、ticinfectionareverycommon,especiallyinchildren.2024/8/29SIGNS & SYMPTOMS Symptoms: 50-75% of adults； 10% of kids (7 daysRoute of transmission Sexual routes Parenteral routescontaminated blood and blood components by transfusion, needle sharing, acupuncture针灸, sharing razors, nail clippers, or tattoo
6、ing Vertical infection Epidemiology2024/8/225400 million carriers (major sources for viral spreading)120 million in China2024/8/226Geographic Distribution of Chronic HBVhttp:/www.who.int/ith/en/PathogenesisCell mediated immunopathogenic damage (CTL). An insufficient T-cell response to the infection
7、generally results in mild symptoms, an inability to resolve the infection, and the development of chronic hepatitisImmune complexes formed between HBsAg and anti-HBs (hypersensitivity reactionstype III) (vasculitis血管炎血管炎, arthralgia关节痛关节痛, rash, and renal damage.)2024/8/227Clinical outcomes of hepat
8、itis B infectionadults(5%)/perinatallyinfectedchildren(95%)2024/8/228The WHO estimates that 80% of all cases of PHC can be attributed to chronic HBV infections.HBV may induce PHC by promoting continued liver repair and cell growth in response to tissue damageThe HBV genome can integrate into the hos
9、t chromosome and stimulating cell growth directly.Primary Hepatocellular Carcinoma2024/8/229AgHBsAg:indicatesvirusreplication;HBsAg6months-progressiontochronicinfection.HBeAg:activeviralreplicationAbAnti-HBs:indicatesrecoveryfrominfection,oracquiredimmunityafterpreventivevaccination.Anti-HBe:occursa
10、fterrecoveryfromacuteinfection,andlessoftenduringthechronicphase.Anti-HBc(IgM):amarkerofacuteinfectionAnti-HBc(IgG):indicatespreviouslyinfectionorchronicinfection.HBV-DNA:q-PCRtests.Thevirusloadinblood.Lab. Diagnosis 2024/8/2302024/8/2Symptoms begin 90 days after exposure (long incubation time)Both
11、Acute and Chronic secrete viral antigens in blood HBsAg/HBeAg Therefore, no detectable anti-HBs/HBe antibodiesAnti-HBV antibodies HBcAb - has been infected, resolved or ongoing HBsAb - vaccination or resolutionAcutehepatitisBChronichepatitisB31PreventionPHC is the first vaccine-preventable human can
12、cer because immunization with HBsAgActive immunizations: HBs particles produced from yeastGiven 0，1 and 6 monthsPassive immunization: Hepatitis B immune globulin within a week of exposurenewborn infants of HBsAg-positive mothers.2024/8/232TreatmentNo treatment for acute infectionFor chronic, three c
13、linical data are required: HBeAg, HBV DNA, ALT (liver enzyme)Anti-HBV-drug Interferon alpha (strong side)Anti-viral reverse transcriptase: lamivudine, adefovir, entecavir, telbivudine, tenofovirHowever, drug-resistant HBV arises2024/8/233Hepatitis C virus2014-Cure for HCV2024/8/234Biological Propert
14、ies HCV is a member of the flavivirus (黄病毒) Enveloped virion +ss RNA At least six different genotypes 2024/8/235EpidemiologyHCV is transmitted by means similar to HBV.Other includes mother-to infant infections and infections related to medical care1992, blood screen for HCV was introduced.2024/8/236
15、170millionpeoplegloballyhavechronichepatitisCinfection.2024/8/237Outcomes of HCV infectionThe average incubation period is 67weeks.More commonly (80), the initial disease is asymptomatic but establishes chronic persistent disease.2024/8/238ClinicalandserologiceventsassociatedwithhepatitisCvirusinfec
16、tion.2024/8/239Laboratory diagnosisSerologyELISAbasedAnti-HCVantibodiesusedforscreentheblood.HCV-specificIgGindicatesexposure,notinfectivity.RT-PCRHCVRNAdetectionisthegoldstandardUsedtogenotypeHCVisolates,followingthesuccessofanit-viraltherapy.DuetothefactthatacuteHCVinfectionisusuallyasymptomatic,e
17、arlydiagnosisoftheHCVinfectionisrare.2024/8/240HCV infection is diagnosed in 2 steps:1. Screening for anti-HCV antibodies with a serological test.2. If anti-HCV antibodies is positive, RT-PCR test for HCV RNA is needed to confirm chronic HCV infection because about 1545% of people infected with HCV
18、spontaneously clear the infection. 2024/8/241Treatment and Prevention Combination therapy interferon-alpha (strong side effects) ribavirin (anti-viral RNA polymerase)New treatment NO VaccineNucleostide anlogueFDA Approvedin Dec. 201390%, clear HCV2024/8/242 Treatment2024/8/243Treatment and Preventio
19、n Combination therapy interferon-alpha (strong side effects) ribavirin (anti-viral RNA polymerase)New treatment NO VaccineNucleostide anlogueFDA Approvedin Dec. 201390%, clear HCV2024/8/244Hepatitis D virus -ssRNA, circular Enveloped with HBsAg,cannot produce viruses without HBV subviral agent, or s
20、atellite virusencodes a single protein, delta antigen responsible for causing 40% of fulminant hepatitis2024/8/2452024/8/2Super-infectionCo-infection Chronic hepatitis High risk of chronic liver disease (70-80%), progressing to cirrhosis and PHC HBV alone is 10-30%Severe acute hepatitis Fulminant he
21、patitisBut, low risk of chronic infection (1-3%)Clinical Syndromes46Geographic Distribution of HDV InfectionHDVPrevalenceHighIntermediateLowVeryLowNoDataTaiwanPacificIslandsTransmission: similar to HBV, primarily through blood2024/8/247Diagnosis, Prevention, and TreatmentAnti-HDV antibodies, delta antigen, HDV RNA HBV vaccineInterferon treatmentMyrcludex B is a novel drug candidate for the treatment of chronic viral hepatitis B and D2024/8/248Hepatitis Viruses 2024/8/2492024/8/250
