Hepatite virale A-E

Hepatitis A Virus

Hepatita virala A

Familia-Picornaviridae Genul-Hepatovirus Specie-HAV Infectie a ficatului cauzat de un virus de tip ARN+,liniar.

Transmis prin ingerarea alimentelor contaminate.Primul virus hepatic descoperit,cunoscut ca fiind cea mai frecventa cauza de inflamatie

Hepatita A-caracteristici morfobiologice

Virusul depistat in 1973 prin imunomicroscopie electronica.
Primul vaccin -1992,cu 7 genotipuri,cu gazde-oameni,maimute

Cultivat-biologic in marmoze,cimpanzei,pe celule de hepatocarcinom uman,pe celule diploide umane ,celule din rinichi de maimuta Structural detine o capsida-icosaedrica,din 60 capsomeri,compusi fiecare din 4 polipeptide VP1,VP2,VP3,VP4.

Hepatita A-caracteristici clinice

Perioada de incubatie

15-45 zile

Debut-simptome nespecifice (oboseala,stare de slabiciune,anorexie,greata,varsaturi,durere abdominala,dureri de cap,eruptii cutanate,diaree.

Dupa 1-2 saptamini se poate instala icterul.Gradul de contagiune cel mai ridicat,concentratia de virusimaxima

Marcheri virali in cursul maladiei

1.HAV (Ag viral) (mase fecale, snge) n ultimele 2 sptmni de incubaie i cteva zile de la apariia icterului 2.IgM anti-HAV sint depistate de la debutul fazei icterice, titru maxim peste o sptmn i dispar dup 8-12 sptmni. 3.IgG anti-HAV persist toat viaa 4.ARN viral (n mase fecale, snge, hepatocite)

Virusul devine inactiv la temperaturi mai mari de 85C, insa in conditii normale de mediu, virusul hepatic A poate supravietui in afara corpului uman si cateva luni. Rezisten virusului este total la 60 grade 1 or, parial la 12 ore, rezist la concentratii de clor uzuale. E inactivat de formol, beta-propiolacton, UV, hipoclorit de sodiu

Diagnostic de laborator

Prelevate-materii fecale,singe,urina 1) Diagnosticul rapid se face prin imunomicroscopie electronica, radioimunotestare si ELISA. - Prin imunomicroscopie electronica virionii se evidentiaza in extractul fecal ,daca concentratia e mai mare sau egala cu 10 la a 4. Se amesteca extract 1020 % din materii fecale cu ser imun specific in raport 9 la unu. Se incubeaza la 37 grade Celsus si se centrifugheaza 30 minute la 10 000 rpm, dupa care se decanteaza supernatantul si se examineaza sedimentul la microscopul electronic.

-O sensibilitate inalta o are si ELISA,care de asemenea evidentiaza antigenul viral utilizind anticorpi marcati cu peroxidaza.

2) Diagnosticul biochimic (metoda

nespecifica) se face paralel. In serul sangvin se dozeaza aldolaza, alaninaminotransferaza, aspartataminotransferaza, bilirubina.

3) Diagnosticul serologic se bazeaza pe

evidentierea anticorpilor IgM si IgG. In acest scop se folosesc ELISA,analiza radioimuna(ARI) si reactia de fixare a complementului (RFC).

Preparate biologice pentru diagnostic si profilaxie specifica

Truse cu imunoglobuline marcate pentru depistarea antigenica rapida a virusului hepatite A;

-truse cu antigen viral si imunoconjugate pentru depistarea anticorpilor IgM si IgG antivirus hepatita A;

-imunoglobulina umana standart, care , administrate in doze de 0,1 ml/kg corp,previne boala la cntactii familiali si din colectivitati de copii.

Transmiterea hepatitei virale A

cai de transmitere
-ingerarea alimentelor si a apei ce au
intrat in contact cu materii fecale infectate; -omiterea procesului de spalare a mainilor dupa utilizarea toaletei; -utilizarea instrumentelor de mancat/baut folosite in prealabil de o persoana infectata; -sexul neprotejat (de orice forma inclusiv oral si anal.

Grupuri de risc

copii care traiesc in comunitati precum crese, gradinite etc.;

adulti care traiesc in conditii aglomerate si nesanitare; vizitatori ai tarilor cu prevalenta ridicata de hepatita A; persoanele active sexual

Prevenirea infectiei
Vaccinarea
.

Injectarea cu imuno-glubulina,gama globulina Imuno-globulina este un preparat care contine un nivel ridicat de anticorpi ai virusului hepatic A si se administreaza de regula persoanelor expuse la virus.

spalarea mainilor cu apa si sapun dupa fiecare utilizare a baii, inainte si dupa prepararea si mancarea alimentelor sau dupa schimbarea scutecelor; evitarea mancarurilor insuficient gatite (fierte, coapte, prajite) protejarea in timpul contactelor sexuale (de orice tip)

Acute Hepatitis B Virus Infection with Recovery

Typical Serologic Course

Symptoms HBeAg anti-HBe

Total anti-HBc

Titre
HBsAg IgM anti-HBc anti-HBs

12 16 20 24 28 32 36

52

100

Weeks after Exposure

Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course

Acute (6 months) HBeAg HBsAg Total anti-HBc Chronic (Years) anti-HBe

Titre

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36

52

Years

Weeks after Exposure

Outcome of Hepatitis B Virus Infection by Age at Infection 100

Chronic Infection (%)

100 80

80

Symptomatic Infection (%)

60

Chronic Infection
Chronic Infection (%)

60

40

40

20

20

Symptomatic Infection
0 Birth 1-6 months 7-12 months 1-4 years 0 Older Children and Adults

Age at Infection

Hepatita virala E
Infectie acuta a ficatului Cauzata de virus de tip ARN+(HEV-depistat in 1983 prin microscopie electronica. Familia-Hepevidae

Genul-Hepevirus

Virusul hepatic E nu cauzeaza infectii cronice ale ficatului, insa, in situatii foarte rare, poate conduce la afectiuni hepatice mai grave. Dimensiunile sale sint incardate in 27-30 nm. Detine o capsid icosaedric (protein unic glicozilat) . HEV se repartizeaz n 3 grupe genomice: I asiatic, II mexican, III nord-american (include i tulpini porcine)

Hepatita virale E-caracteristici clinice

Perioada de incubatie-15-60 zile Apare in materii fecale inainte cu aparitia afectiunii clinice si persista 7-14 zile dupa aceasta Materiile fecale sunt deosebit de contagioase
Desi hepatita E nu cronicizeaza niciodata, exista situatii foarte rare cand aceasta afectiune poate cauza insuficienta hepatica pentru ca distruge prea multe celule ale ficatului (1-2%), insa poate cauza moartea

Diagnosis

A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection. HBsAg - used as a general marker of infection. HBsAb - used to document recovery and/or immunity to HBV infection. anti-HBc IgM - marker of acute infection. anti-HBcIgG - past or chronic infection. HBeAg - indicates active replication of virus and therefore infectiveness. Anti-Hbe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV. HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.

Treatment

Interferon - for HBeAg +ve carriers with chronic active hepatitis. Response rate is 30 to 40%.

alpha-interferon 2b (original) alpha-interferon 2a (newer, claims to be more efficacious and efficient)

Lamivudine - a nucleoside analogue reverse transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapid emergence of drug resistance. Adefovir less likely to develop resistance than Lamivudine and may be used to treat Lamivudine resistance HBV. However more expensive and toxic Entecavir most powerful antiviral known, similar to Adefovir Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.

Prevention

Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries.
Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive. Other measures - screening of blood donors, blood and body fluid precautions.

Hepatitis C Virus
capsid envelop e protein c22 protease/helica se 33c c-100 RNA- RNA polymerase dependent

5
cor E1 e E2 NS 2 NS 3 NS 4 NS 5

hypervariable region

Hepatitis C Virus

Genome resembled that of a flavivirus positive stranded RNA genome of around 10,000 bases 1 single reading frame, structural genes at the 5' end, the non-structural genes at the 3' end. enveloped virus, virion thought to 30-60nm in diameter morphological structure remains unknown

HCV has been classified into a total of six genotypes (type 1 to 6) on the basis of phylogenetic analysis Genotype 1 and 4 has a poorer prognosis and response to interferon therapy, In Hong Kong, genotype 1 accounts for around 67% of cases and genotype 6 around 25%.

Terminology
Family Genus Species Genotype Subtype Quasispecies

Term

Definition

% Nucleotide Similarity 65.7-68.9

Genotype

Genetic heterogeneity among different HCV isolates Closely related isolates within each of the major genotypes Complex of genetic variants within individual isolates

Subtype

76.9-80.1

Quasispecies

90.8-99

Hepatitis C - Clinical Features

Incubation period:
Clinical illness (jaundice):

Average 6-7 wks Range 2-26 wks 30-40% (20-30%) 70%

85-100% No protective antibody response identified

Chronic hepatitis:
Persistent infection: Immunity:

Chronic Hepatitis C Infection

The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection. All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.

Hepatitis C Virus Infection

Typical Serologic Course
Symptoms

antiHCV

Titre

ALT

Normal 0 1 2 3 4 5 6 Month s Time after 1 2 3 Years 4

Exposure

Risk Factors Associated with Transmission of HCV

Transfusion or transplant from infected donor Injecting drug use Hemodialysis (yrs on treatment)

Accidental injuries with needles/sharps

Sexual/household exposure to anti-HCV-positive contact

Multiple sex partners

Birth to HCV-infected mother

Laboratory Diagnosis

HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears. HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.

HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.

Prognostic Tests

Genotyping genotype 1 and 4 have a worse prognosis overall and respond poorly to interferon therapy. A number of commercial and inhouse assays are available.

Genotypic methods DNA sequencing, PCR-hybridization e.g. INNOLIPA. Serotyping particularly useful when the patient does not have detectable RNA.

Viral Load patients with high viral load are thought to have a poorer prognosis. Viral load is also used for monitoring response to IFN therapy. A number of commercial and in-house tests are available.

Treatment

Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment. Ribavirin - there is less experience with ribavirin than interferon. However, recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone.

Prevention of Hepatitis C
Screening of blood, organ, tissue donors
High-risk behavior modification Blood and body fluid precautions

Hepatitis D (Delta) Virus

antigen HBsAg

RNA

Hepatitis D Virus

The delta agent is a defective virus which

shows similarities with the viroids in plants. The agent consists of a particle 35 nm in diameter consisting of the delta antigen surrounded by an outer coat of HBsAg. The genome of the virus is very small and consists of a single-stranded RNA

Hepatitis D - Clinical Features

Coinfection severe acute disease. low risk of chronic infection. Superinfection usually develop chronic HDV infection. high risk of severe chronic liver disease. may present as an acute hepatitis.

Hepatitis D Virus Modes of Transmission

Percutanous exposures injecting drug use

Permucosal exposures
sex contact

HBV - HDV Coinfection

Typical Serologic Course
Symptoms ALT Elevated

Titre
IgM anti-HDV

anti-HBs

HDV RNA HBsAg Total anti-HDV

Time after Exposure

HBV - HDV Coinfection

Typical Serologic Course
Symptoms ALT Elevated

Titre
IgM anti-HDV

anti-HBs

HDV RNA HBsAg Total anti-HDV

Time after Exposure

HBV - HDV Superinfection

Typical Serologic Course
Jaundice Symptoms ALT Total anti-HDV

Titre

HDV RNA HBsAg IgM anti-HDV

Time after

Hepatitis D - Prevention

HBV-HDV Coinfection
Pre or postexposure prophylaxis to prevent HBV infection.

HBV-HDV Superinfection
Education to reduce risk behaviors among persons with chronic HBV infection.

Hepatitis E Virus

Hepatitis E Virus

Calicivirus-like viruses unenveloped RNA virus, 32-34nm in diameter +ve stranded RNA genome, 7.6 kb in size. very labile and sensitive Can only be cultured recently

Hepatitis E - Clinical Features

Incubation period:
Case-fatality rate:

Illness severity: Chronic sequelae:

Average 40 days Range 15-60 days Overall, 1%-3% Pregnant women, 15%-25% Increased with age
None identified

Hepatitis E Virus Infection

Typical Serologic Course Symptoms
ALT
IgG anti-HEV

Titer
Virus in stool

IgM anti-HEV

1 0

1 1

1 2

1 3

Weeks after Exposure

Hepatitis E Epidemiologic Features

Most outbreaks associated with faecally contaminated drinking water. Several other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico. In the United States and other nonendemic areas, where outbreaks of hepatitis E have not been documented to occur, a low prevalence of anti-HEV (<2%) has been found in healthy populations. The source of infection for these persons is unknown. Minimal person-to-person transmission.

Prevention and Control Measures for Travelers to HEV-Endemic Regions

Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit/vegetables not peeled or prepared by traveler. IG prepared from donors in Western countries does not prevent infection. Unknown efficacy of IG prepared from donors in endemic areas.

Vaccine?