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DNA Virus and Hepatitis Viruses

VIEWS: 17 PAGES: 40

									Hepatitis viruses
      http://zamberi.tripod.com/index




             Dr Zamberi Sekawi
 BSc (Med), MD (UKM), MPath (Microbiol), AM (M’sia)
        Clinical Microbiologist
Faculty of Medicine & Health Sciences
      University Putra Malaysia
VIRAL HEPATITIS
   Hepatitis   A virus
   Hepatitis   B virus
   Hepatitis   C virus
   Hepatitis   D virus
   Hepatitis   E virus
   Hepatitis   G virus

   Future:
   ? Hepatitis H virus
   ? Hepatitis I virus
   ? Hepatitis J virus
   Etc…
HEPATITIS A VIRUS


                    Picornaviridae
                    Hepatovirus
                    Non-envelope, single-
                       stranded RNA,
                       positive sense.
                    Only one serotype.
Incubation period:    2 – 6 weeks

Transmission:
• faecal-oral
• food/water
• blood product

Associated with poor personal hygiene and
  overcrowding.
More symptomatic in adults.
Symptoms

Constitutional symptoms of anorexia, nausea
  and vomiting, fatigue, malaise, arthralgias,
  myalgias, headache, photophobia, pharyngitis,
  cough, and coryza may precede the onset of
  jaundice by 1 to 2 weeks.
Nausea, vomiting, and anorexia are frequently
  associated with alterations in olfaction and
  taste.

Dark urine and clay-coloured stools may be
  present.
Tender hepatomegaly.
Fulminant hepatitis occurs in elderly and patients
  with underlying liver disease.
Presentation:
  Severe jaundice, neurological changes,
  coagulopathy, renal failure, cardiopulmonary
  failure.
High mortality rate.
Lab diagnosis

Serology:

IgM positive: recent
  hepatitis A

IgG positive:
  past hepatitis A
Prevention

Passive immunisation
Anti-HAV preparation.
Used in post-exposure prophylaxis.

Active immunisation
Formalin-inactivated vaccine.
Approved for use in those > 2 years old.
Recommended to selected groups of people, e.g.
  travellers, food handlers, laboratory workers, etc.
Adults: 0, 6 - 12 months
Children: 0, 1, 6 – 12 months
HEPATITIS B VIRUS
  Hepadnavirus
  double-stranded DNA

  HBsAg -- Anti-HBs
  HBeAg -- Anti-HBe
  HBcAg -- Anti-HBc
350 million chronic carriers world-wide.
Malaysia:  5%
Prevalence is highest in China, Africa (Sub-Sahara), South
   East Asia and among Eskimos.

Transmission:
1. Blood product
2. Vertical transmission (predominant in endemic areas)
3. Sexual transmission
4. Intravenous drug abuse
                     Outcome in adult


Acute Hepatitis B   Subclinical infection    Chronic carriers
     (25%)                 (65%)                 (10%)



                    Outcome in neonates


        Acute Hepatitis B and       Chronic carriers
        Subclinical infection           (90%)
               (10%)
                              Adults

                                          10%
                        65%
                                  25%

Subclinical infection         Acute             Chronic Carrier


                                   <1%



                              Fulminant            Cirrhosis
                              Hepatitis




                                                 Hepatocellular
       Lifelong                                   Carcinoma
      Immunity                  Death
Acute hepatitis B




  (1) Incubation period: 1 – 6 months.
      HBsAg and HBeAg start to increase during this period.
      Patient is infectious.
  (2) Acute symptoms:
      Jaundice, fever, nausea, right hypochondriac pain.
      ALT reaches high level.
(3) The appearance of anti-HBe and anti-HBc antibodies.
   HBeAg disappears.
   Symptoms resolving.
(4) Window period
    ‘Window period’= period between disappearance of detectable
    HBsAg and appearance of detectable anti-HBs by standard
    laboratory test.
(5) Patient in convalescent state.
    Anti-HBs, the protective antibody becomes detectable.
(6) Years later.
    IgM anti-HBc disappears in 3 – 12 months.
    IgG anti-HBc and persist for life.
Acute Hepatitis B
Chronic Hepatitis B

The presence of HBsAg in serum for 6 months or longer
   after initial detection.
High risk groups:
1. Neonates
2. immunocompromised host
Majority is asymptomatic.
Minority experiences only mild and intermittent fatigue.
Chronic Hepatitis B




   (1) Immune-tolerant phase
       High viral replication.
       The host is able to tolerate the presence of the virus.
(2) Immune-clearance phase.
   Low viral replication.
   Patient will enter this phase when tolerance to HBV break
   down (about 15 – 35 years later).
   Host actively tries to eradicate virus. Therefore, ALT are
   raised.
   There were increasing production of anti-HBe.
   Most of liver damage happens during this time, leading to
   cirrhosis.
   The longer the duration of this phase, the greater the liver
   damage. Hence the risk of liver cancer is high.
(3) Latent infection phase
    Patient enters this phase once HBV-infected cells are
    destroyed by the immune system.
    Active replication cease and HBeAg disappear.
    ALT normal. Anti-HBe positive.
    HBsAg is still present. ‘Healthy carrier’.
    Anti-HBs is never produced.
Chronic hepatitis B model
Patient will have cirrhosis and eventually die of
   hepatocellular carcinoma (HCC).
Risk of acquiring HCC from chronic hepatitis B is 98 times
   of the normal population.
Lab investigations

Serology:

1. HBsAg:      Presence of virus (acute or chronic)
2. HBeAg:      Active replication of HBV.
3. Anti-HBs: Immunity to HBV either by natural infection
   or vaccination.
4. Anti-HBe: Low viral replication.
5. Anti-HBc: Ongoing or previous HBV infection
   depending on IgM or IgG.
               Acute   Conva   Chr Post-vac
HBsAg            +       -      +     -
HBeAg            +       -     +/-    -
Anti-HBe         -       +     -/+    -
Anti-HBc IgM     +       -       -    -
Anti-HBc IgG     +       +      +     -
Anti-HBs         -       +       -    +
Treatment

Acute hepatitis
Supportive.

Chronic hepatitis
Aim: to help the body to eradicate the virus. (during the
  second phase).

Recommended for patients with:
• persistent levels of ALT in serum
• detectable levels of HBsAg, HBeAg and HBV DNA in
  serum
• liver biopsy suggesting chronic hepatitis and
  compensated liver disease.
Presence of anti-HBe and normal ALT (third phase) will
   indicate the treatment is effective.



1.    interferon
2.   Pegylated  interferon
3.   Lamivudine
4.   Adefovir
5.   Entecavir
Prevention

Three main strategies:
1. behaviour modification
2. active immunoprophylaxis
3. passive immunoprophylaxis

Active immunisation has been very successful.
Standard regimen: 0, 1 and 6 months
Highly efficacious (85 to 95% seroconversion).

Immunocompromised patients respond poorly to the
  vaccine.
Passive immunoprophylaxis is used in:
1. neonates born to HBsAg-positive mothers.
   Anti-HBs immunoglobulins should be given immediately
   after delivery together with the recombinant HBV
   vaccine. (90% protected)
2. after needlestick exposure.
3. after sexual exposure.
4. after liver transplantations in patients who are HBsAg-
   positive pretransplantation.
HEPATITIS C VIRUS


            Flavivirus
            single-stranded RNA, positive sense
            6 genotypes (1 through 6).
Hepatitis C virus mutates very rapidly. Therefore, the
   production of protective antibody is short-lived.
Vaccine production is very difficult.
Worldwide incidence: 1 – 2%
Higher rates in Eastern Europe and Africa (especially
   Egypt).

Genotypes
1a :North and South America, Australia
1b :North America, Europe, Japan
2 :North America, West and Southern Europe
3 :Australia, Southern Asia
4 :Egypt, Central Africa
6 :Asia
Transmission:
1. Blood borne (especially blood transfusion)
2. Injection-drug abuse
3. Vertical transmission (uncommon)
4. Multiple sexual partners

Incubation period: 2 weeks

Associated with extrahepatic manifestation.
  E.g. mixed cryoglobulinaemia and
  membranoproliferative glomerulonephritis.
              Primary
             Hepatitis C


5 – 20%                        80 - 95%

                           Persistance infection
Clearance
                           (Chronic Hepatitis C)




                                 Cirrhosis

                            20 years

                              Hepatocellular
     DEATH
                                carcinoma
Laboratory diagnosis

1. Screening: Serology. e.g. ELISA.

2. Confirmation:       Immunoblot assay e.g. RIBA, LIA
                       Genome detection. e.g. PCR.
Treatment and prevention

Treatment:
a) IFN  monotherapy
   Sustained response rate for:
       6-month therapy = 10 – 20%
       12 – 18-month therapy = 15 – 30%
b) Combination IFN  and ribavirin
   Sustained response rate:  40%

(Sustained response: normal ALT  undetectable HCV RNA
  6 months after completion of therapy)
Interferon therapy is indicated in patients who are at the
   greatest risk for progression to cirrhosis:
1. Persistently elevated ALT > 6 months.
2. Detectable serum HCV RNA by a qualitative or
   quantitative assay.
3. Liver biopsy = grade 2 or 3 fibrosis.
4. Moderate degrees of liver inflammation and necrosis.

No vaccine is available.
HEPATITIS D VIRUS


               a.k.a. delta hepatitis
                  agent.
               Defective RNA virus,
                  requires HBV for its
                  replication.
Worldwide distribution with endemicity in the
  Mediterranean countries.
HDV can either:
 infect a person simultaneously with HBV (coinfection) or
 superinfect a person already infected with HBV
  (superinfection).

Duration of HDV infection is determined by duration of
  HBV infection.
Serology
No specific treatment.
Prevention by giving HBV vaccine.
 HEPATITIS E VIRUS



Non-envelope, single-stranded RNA, positive sense.
World wide distribution.
Causes acute hepatitis. High mortality among pregnant
  women.
HEPATITIS G VIRUS

Also known as GBV-C.
Genome: single-stranded RNA, positive sense.
25% similar to hepatitis C.

Transmission:
1.   Blood transfusion
2.   Injecting drug users

Hepatic damage appears to be mild or absent.
Role as a causative agent is still questionable.
Enquiries:

03 – 8946 8459
zamberi@medic.upm.edu.my
szamberi@yahoo.com

http://zamberi.tripod.com/index

								
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