Viral hepatitisViral hepatitis
Changes in liver in patients with Changes in liver in patients with
hepatitishepatitis
Cirrhosis Hepatocellular carcinoma
Local destruction in hepatocytes
Norm Fibrose
General features of General features of viral hepatitisviral hepatitis
Viruses of hepatitis affect only humansViruses of hepatitis affect only humans ( (anthroponosis anthroponosis ))Routs of transmissionRouts of transmission – – parenteral and parenteral and ansans fecal-oral fecal-oral routerouteAll agents are viruses that quite resistant in environment All agents are viruses that quite resistant in environment Main organ-goal is liver Main organ-goal is liver ((hepatocytes)hepatocytes)Main pathogenic mechanism is immunodependent Main pathogenic mechanism is immunodependent damage of hepatocytesdamage of hepatocytesSimilar development of disease and clinical symptoms Similar development of disease and clinical symptoms (jaundice(jaundice))After infection type-specific immunity is developed After infection type-specific immunity is developed Chronic carriers and complication with cirrhosis and Chronic carriers and complication with cirrhosis and hepatocellular carcinona are possiblehepatocellular carcinona are possibleGenetic changeableness is common for most of hepatitis Genetic changeableness is common for most of hepatitis viral agentsviral agents
Spreading of viral hepatitisSpreading of viral hepatitis
Incidence graphs for hepatitisIncidence graphs for hepatitis
Obligate hepatotropic virusesObligate hepatotropic viruses
ss – single-strandedds – double-stranded
Virus Virus Family Family Genome Genome Structure Structure HAVHAV PicornaviridaePicornaviridae sslssl RNA RNA ++ Nonenveloped Nonenveloped
HBVHBV HepadnaviridaeHepadnaviridae частково длц частково длц DNADNA Enveloped Enveloped
HCVHCV FlaviviridaeFlaviviridae sslssl RNARNA + + EnvelopedEnveloped
HDVHDV DeltavirusDeltavirus sscssc RNARNA - - EnvelopedEnveloped
HEVHEV CaliciviridaeCaliciviridae sslssl RNARNA + + Nonenveloped Nonenveloped
HGVHGV FlaviviridaeFlaviviridae sslssl RNARNA + + EnvelopedEnveloped
TTVTTV ParvoviridaeParvoviridae sscssc DNADNA Nonenveloped Nonenveloped
SENVSENV CirkoviridaeCirkoviridae sscssc DNADNA Nonenveloped Nonenveloped
l- linearc – circular
Geographic distribution of Hepatitis Geographic distribution of Hepatitis A virus infectionA virus infection
Hepatitis A virus (Hepatovirus)Hepatitis A virus (Hepatovirus)
Family Picornaviridae, genus Hepatovirus
Nonenveloped viruses with cubical type of symmetry
Small - diameter 20-30 nm
Genome – single-stranded linear RNA
RNA has positive polarity
It has one serotype
HAV has a replicative cycle similar to that of enteroviruses (Family Picornaviridae)
HAV disease is far milder, shorter-term, and less virulent than the other forms of hepatitis
Structure of HAVStructure of HAV
5’ end of RNA has a protein that serves as a primer for transcription by RNA polymerase
Hepatitis A rate, by age and gender Hepatitis A rate, by age and gender (United States, 1990)(United States, 1990)
Transmission – fecal-oral route.
Hepatitis A rate, by age and gender Hepatitis A rate, by age and gender (United States, 2001)(United States, 2001)
Events in hepatitis A virus infectionEvents in hepatitis A virus infection
Concentration of Hepatitis A virus Concentration of Hepatitis A virus in various body fluidsin various body fluids
Treatment and prevention of Treatment and prevention of hepatitis Ahepatitis A
Treatment.Treatment. NNo antiviral therapyo antiviral therapy is available is available
PreventionPrevention::Active immunizationActive immunization with a vaccine containing hepatitis with a vaccine containing hepatitis A viruses that are A viruses that are inactivatedinactivated by formalin by formalin
Passive immunizationPassive immunization with immune serum globulin prior with immune serum globulin prior to infection or early in the incubation period for prevent to infection or early in the incubation period for prevent or mitigate the diseaseor mitigate the disease
Geographic distribution of Hepatitis Geographic distribution of Hepatitis B virus infectionB virus infection
High Intermediate Low
Electron micrograph ofElectron micrograph of Hepatitis B viruses Hepatitis B viruses
Hepatitis B virusHepatitis B virus
Family Hepadnaviridae
Small - diameter 42 nm
HBV virion also is named a Dane particle
Nucleocapsid has cubical type of symmetry
Enveloped viruses
The envelope contains a protein called the surface antigen (HBsAg)
Genome – partially double-stranded circular DNA
Nucleocapsid contains DNA-dependent DNA polymerase
HBV cannot be cultivated in vitro
Humans are the only natural hosts of HBV
Some members of hepadnaviridae family infect certain rodents and ducks (but not HBV)
Three different types of a prticlesThree different types of a prticles
42-nm virions
22-nm spheres
Filamentous 22 nm wide and approximately 200 nm long
Electron micrograph of different Electron micrograph of different types of HBVtypes of HBV
Structure of HBV particlesStructure of HBV particles
HBV antigensHBV antigens
HBsAg - hepatitis B surface antigen
HBcAg – hepatitis B core antigen
HBeAg –hepatitis B e antigen
Nucleic acid of HBVNucleic acid of HBV
Events during reproduction of HBV (1)Events during reproduction of HBV (1)
Adherence with viral HBsAg
Events during reproduction of HBV (2)Events during reproduction of HBV (2)
Some of the formed double-stranded closed-circular DNA integrates into the hepatocyte DNA (provirus)
Events during reproduction of HBV (3)Events during reproduction of HBV (3)
HBs
The three main modes of The three main modes of transmission of hepatitis Btransmission of hepatitis B
During sexual intercourseDuring sexual intercourse Perinatally from mother to newbornPerinatally from mother to newborn Via bloodVia blood
The clinical features of hepatitis BThe clinical features of hepatitis B
Man with jaundice caused by HBVMan with jaundice caused by HBV
Hepatocellular carcinoma (hepatoma) Hepatocellular carcinoma (hepatoma) associated with HBV-infectionassociated with HBV-infection
Laboratory diagnosis of hepatitisLaboratory diagnosis of hepatitis BB
Immunoassay for HBsAg is used for detection of Immunoassay for HBsAg is used for detection of early acute HBV infection (early acute HBV infection (immunofluorescence immunofluorescence assay ELISA or radioimmunoassayassay ELISA or radioimmunoassay).). HBsAg HBsAg disappears from the blood after 24 weeks.disappears from the blood after 24 weeks.In 2 weeks after HBsAg, In 2 weeks after HBsAg, HBcAbHBcAb (antibody to (antibody to HBcAg) appears in blood and is always positive HBcAg) appears in blood and is always positive and can be used to make the diagnosis and can be used to make the diagnosis ((immunoassayimmunoassay))Detection of Detection of HBsAbHBsAb (antibody to HBsAg) with (antibody to HBsAg) with immunoassayimmunoassay Detection of Detection of viral DNA with PCRviral DNA with PCR
Window period
Serologic test results in four stages Serologic test results in four stages of HBV infectionof HBV infection
Test Test Acute Acute diseasedisease
Window Window phasephase
Complete Complete recoveryrecovery
Chronic Chronic carries carries statestate
HBsAgHBsAg Positive Positive NegativeNegative NegativeNegative Positive Positive
HBsAbHBsAb Negative Negative NegativeNegative Positive Positive NegativeNegative
HBcAbHBcAb Positive Positive Positive Positive Positive Positive Positive Positive
Treatment and preventionTreatment and prevention
TreatmentTreatment.. Alpha interferon is clinically useful Alpha interferon is clinically useful for treatment of chronic hepatitis Bfor treatment of chronic hepatitis B
PreventionPrevention::Active immunizationActive immunization with vaccine: with vaccine:
Modern vaccine contains HBsAg produced in yeasts Modern vaccine contains HBsAg produced in yeasts by genetic engineering techniques by genetic engineering techniques Prior vaccine is inactivated vaccine consisting of Prior vaccine is inactivated vaccine consisting of HBsAg prepared from spherical particles purified from HBsAg prepared from spherical particles purified from the serum of infected individuals. the serum of infected individuals.
Passive immunizationPassive immunization with hepatitis B immune with hepatitis B immune globulin contains HBsAb (it is prepared from sera of globulin contains HBsAb (it is prepared from sera of patients who have recovered from hepatitis Bpatients who have recovered from hepatitis B
Geographic distribution of HDV Geographic distribution of HDV infectioninfection
Hepatitis D virus (delta agent)Hepatitis D virus (delta agent)
Delta hepatitis virus is a defective virus
Can not replicate by itself, because it does not have the genes for its protein coat
HDV can replicate only in cells also infected with HBV
Enveloped virus
Genome – single-stranded RNA with negative polarity, covalently closed circle.
The RNA of HDV is very small and encodes only one protein, the internal core protein called delta antigen
Structure of HDVStructure of HDV
HDV uses the surface antigen of HBV (HBsAg) as a coat
HDV is transmitted by the same HDV is transmitted by the same means as is HBVmeans as is HBV
Sexually Sexually Perinatally Perinatally By bloodBy blood
HBV-HDV coinfectionHBV-HDV coinfection
HBV-HDV superinfectionHBV-HDV superinfection
Laboratory diagnosis of hepatitis DLaboratory diagnosis of hepatitis D
Detection of delta antigen with immunoassayDetection of delta antigen with immunoassay Detection of IgM antibody to delta AgDetection of IgM antibody to delta Ag
No specific antiviral therapyNo specific antiviral therapy
No vaccine against HDVNo vaccine against HDV
Geographic distribution of HCV Geographic distribution of HCV infectioninfection
Hepatitis C virusHepatitis C virus
Family Flaviviridae
Enveloped virus
Nucpeocapsid with cubical type of symmetry
Genome – single-stranded, positive polarity RNA
No virion polymerase
Multiple serotypes exist, the gene encoding the envelope glycoprotein has hypervariable regions
HCV has not grown in cell culture
Structure of hepatitis C virusStructure of hepatitis C virus
HCV is transmitted by the same HCV is transmitted by the same means as is HBVmeans as is HBV
Sexually Sexually From mother to child From mother to child Via bloodVia blood
Laboratory diagnosis of hepatitis CLaboratory diagnosis of hepatitis C
Detection of antibodies to HCV in an ELISADetection of antibodies to HCV in an ELISA Detection of viral RNA in PCRDetection of viral RNA in PCR
Alpha interferon is used for the treatment of Alpha interferon is used for the treatment of chronic hepatitis Cchronic hepatitis C
There is no vaccine against HCV, and There is no vaccine against HCV, and immunoglobulins are not available immunoglobulins are not available
Geographic distribution of HEV Geographic distribution of HEV infectioninfection
Hepatitis E virusHepatitis E virus
Family Caliciviridae
Small, nonenveloped virus
Genome – single-stranded RNA
Transmission by fecal-oral rout
Clinically the disease resembles hepatitis A
Chronic liver disease does not occur
Diagnosis is typically made by excluding HAV and other causes
There is no antiviral treatment and no vaccine
Clinical features of hepatitis virusesClinical features of hepatitis virusesVirus Virus Mode of Mode of
transmisstransmission ion
Incuba-Incuba-tion tion periodperiod
Chronic Chronic carrierscarriers
Laboratory Laboratory diagnosis diagnosis ((immunoassay, immunoassay, PCRPCR))
VaccinVaccinee
HAVHAV Fecal-oralFecal-oral 3-5 weeks3-5 weeks No No IgM HAV. IgM HAV.
RNARNAYes Yes
HBVHBV Parenteral Parenteral 10-15 10-15 weeksweeks
Yes Yes HBsAg, HBsAb, HBsAg, HBsAb, IgM HBcAb. DNAIgM HBcAb. DNA
Yes Yes
HCVHCV Parenteral Parenteral 5-9 weeks5-9 weeks Yes Yes HCV Ab.HCV Ab.
RNARNANo No
HDVHDV Parenteral Parenteral With coin-With coin-fection, fection, same as same as HBVHBV
Yes Yes Ab to delta Ag. Ab to delta Ag.
RNARNANo No
HEVHEV Fecal-oralFecal-oral ?? No No None None No No