hepatitis viruses dr zamberi sekawi bsc (med), md (ukm), mpath (microbiol), am (m’sia) clinical...
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Hepatitis viruses http://zamberi.tripod.com/index
Dr Zamberi SekawiBSc (Med), MD (UKM), MPath (Microbiol), AM (M’sia)
Clinical MicrobiologistFaculty of Medicine & Health Sciences
University Putra Malaysia
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VIRAL HEPATITIS
Hepatitis A virusHepatitis B virusHepatitis C virusHepatitis D virusHepatitis E virusHepatitis G virus
Future:? Hepatitis H virus? Hepatitis I virus? Hepatitis J virusEtc…
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HEPATITIS A VIRUS
PicornaviridaeHepatovirusNon-envelope, single-
stranded RNA, positive sense.
Only one serotype.
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Incubation period: 2 – 6 weeks
Transmission:• faecal-oral• food/water• blood product
Associated with poor personal hygiene and overcrowding.
More symptomatic in adults.
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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.
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Fulminant hepatitis occurs in elderly and patients with underlying liver disease.
Presentation: Severe jaundice, neurological changes, coagulopathy, renal failure, cardiopulmonary failure.
High mortality rate.
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Lab diagnosis
Serology:
IgM positive: recent hepatitis A
IgG positive:past hepatitis A
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Prevention
Passive immunisation Anti-HAV preparation. Used in post-exposure prophylaxis.
Active immunisationFormalin-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 monthsChildren: 0, 1, 6 – 12 months
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HEPATITIS B VIRUS
Hepadnavirus double-stranded DNA
HBsAg -- Anti-HBsHBeAg -- Anti-HBeHBcAg -- Anti-HBc
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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 product2. Vertical transmission (predominant in endemic areas)3. Sexual transmission4. Intravenous drug abuse
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Acute Hepatitis B( 25% )
S ubcl in ica l in fection( 65% )
C hron ic carriers( 10% )
O utcom e in adu lt
Acute H epatitis B andS ubcl in ica l in fection
( 10% )
C hron ic carriers( 90% )
O utcom e in neonates
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Adults
Subclinical infection
65%
Acute
25%
Chronic Carrier
10%
Cirrhosis
Hepatocellular CarcinomaDeath
Lifelong Immunity
Fulminant Hepatitis
<1%
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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.
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(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.
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(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.
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Acute Hepatitis B
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Chronic Hepatitis B
The presence of HBsAg in serum for 6 months or longer after initial detection.High risk groups:1. Neonates2. immunocompromised host
Majority is asymptomatic. Minority experiences only mild and intermittent fatigue.
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Chronic Hepatitis B
(1) Immune-tolerant phase High viral replication. The host is able to tolerate the presence of the virus.
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(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.
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(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.
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Chronic hepatitis B model
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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.
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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.
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Acute Conva Chr Post-vacHBsAg + - + -HBeAg + - +/- -Anti-HBe - + -/+ -Anti-HBc IgM + - - -Anti-HBc IgG + + + -Anti-HBs - + - +
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Treatment
Acute hepatitisSupportive.
Chronic hepatitisAim: 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.
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Presence of anti-HBe and normal ALT (third phase) will indicate the treatment is effective.
1. interferon 2. Pegylated interferon 3. Lamivudine 4. Adefovir5. Entecavir
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Prevention
Three main strategies:1. behaviour modification 2. active immunoprophylaxis3. passive immunoprophylaxis
Active immunisation has been very successful. Standard regimen: 0, 1 and 6 monthsHighly efficacious (85 to 95% seroconversion).
Immunocompromised patients respond poorly to the vaccine.
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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.
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HEPATITIS C VIRUS
Flavivirussingle-stranded RNA, positive sense6 genotypes (1 through 6).
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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, Australia1b:North America, Europe, Japan2 :North America, West and Southern Europe3 :Australia, Southern Asia4 :Egypt, Central Africa6 :Asia
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Transmission:1. Blood borne (especially blood transfusion)2. Injection-drug abuse3. Vertical transmission (uncommon)4. Multiple sexual partners
Incubation period: 2 weeks
Associated with extrahepatic manifestation. E.g. mixed cryoglobulinaemia and membranoproliferative glomerulonephritis.
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Primary Hepatitis C
Cirrhosis
Hepatocellular carcinomaDEATH
Clearance
5 – 20%
Persistance infection (Chronic
Hepatitis C)
80 - 95%
20 years
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Laboratory diagnosis
1. Screening: Serology. e.g. ELISA.
2. Confirmation: Immunoblot assay e.g. RIBA, LIAGenome detection. e.g. PCR.
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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)
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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.
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HEPATITIS D VIRUS
a.k.a. delta hepatitis agent.
Defective RNA virus, requires HBV for its replication.
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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.
SerologyNo specific treatment.Prevention by giving HBV vaccine.
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HEPATITIS E VIRUS
Non-envelope, single-stranded RNA, positive sense.World wide distribution.Causes acute hepatitis. High mortality among pregnant
women.
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HEPATITIS G VIRUS
Also known as GBV-C. Genome: single-stranded RNA, positive sense.25% similar to hepatitis C. Transmission:1. Blood transfusion2. Injecting drug users Hepatic damage appears to be mild or absent.Role as a causative agent is still questionable.