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