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

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…

HEPATITIS A VIRUS

PicornaviridaeHepatovirusNon-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 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

HEPATITIS B VIRUS

Hepadnavirus double-stranded DNA

HBsAg -- Anti-HBsHBeAg -- Anti-HBeHBcAg -- 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 product2. Vertical transmission (predominant in endemic areas)3. Sexual transmission4. Intravenous drug abuse

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

Adults

Subclinical infection

65%

Acute

25%

Chronic Carrier

10%

Cirrhosis

Hepatocellular CarcinomaDeath

Lifelong Immunity

Fulminant Hepatitis

<1%

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. Neonates2. 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-vacHBsAg + - + -HBeAg + - +/- -Anti-HBe - + -/+ -Anti-HBc IgM + - - -Anti-HBc IgG + + + -Anti-HBs - + - +

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.

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

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.

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

Flavivirussingle-stranded RNA, positive sense6 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, Australia1b:North America, Europe, Japan2 :North America, West and Southern Europe3 :Australia, Southern Asia4 :Egypt, Central Africa6 :Asia

 

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.

Primary Hepatitis C

Cirrhosis

Hepatocellular carcinomaDEATH

Clearance

5 – 20%

Persistance infection (Chronic

Hepatitis C)

80 - 95%

20 years

Laboratory diagnosis

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

2. Confirmation: Immunoblot assay e.g. RIBA, LIAGenome 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.

SerologyNo 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 transfusion2.      Injecting drug users Hepatic damage appears to be mild or absent.Role as a causative agent is still questionable.

Enquiries:

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

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