GIS07 Viral Hepatitis, Serological Tests And Immunization Flashcards

1
Q

Symptoms of hepatitis

A
  1. Pain over R hypochondrium (swelling of liver capsule: pain sensitive)
  2. Jaundice, pale stools, dark urine
  3. Elevated liver enzymes (Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) —> Parenchymal enzymes)
  4. Fever
  5. Loss of appetite, N+V
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2
Q

Aetiology of acute hepatitis

A
  1. Viruses
    - Hepatitis A, B, C, D, E
    - Epstein-Barr virus, Cytomegalovirus, yellow fever virus
  2. Bacteria
    - Leptospirosis, Q fever
  3. Parasites
  4. Toxins + drugs
  5. Autoimmune disease
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3
Q

Faecal-oral hepatitis vs Blood-borne hepatitis

A

Faecal-oral transmission (AE):

  1. Hepatitis A
  2. Hepatitis E
  3. Non-A, Non-B

Blood-borne transmission (BCD):

  1. Hepatitis B
  2. Hepatitis C
  3. Hepatitis D
  4. Non-A, Non-B
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4
Q

Hepatitis B

A
  • DNA virus
  • Hepa-dna-virus
  • enveloped
  • limited nucleotides (3200) —> overlapping open reading frame (ORF) to maximise effect

Transmission:

  • vertical
  • sexual / close physical contact
  • blood products

High risk groups:

  • mother / family members carriers
  • haemophiliacs (impairment to clot blood)

Incubation period:
- 2-6 months

Symptoms:

  • Adults: 50% symptomatic
  • Children: usually asymptomatic —> lead to chronic carrier state

Onset:
- acute / insidious

Fulminant hepatitis
- 0.1-1%

  • **Diagnosis:
  • S antigen in serum
  • E antigen in serum: high infectivity
  • Anti-C IgM
  • HBV DNA
  • NO viral culture

Cross-infection:
- high risk if E antigen +ve

Prevention:

  • passive immunisation: Hyperimmune Hep B Immune Globulin (HBIG)
  • active immunisation: HBV vaccine: genetically engineered vaccine: Anti-S Ab —> all infants + health care workers

Treatment:

  • ***NO curative treatment
  • Immunomodulation: ***IFN-alpha
  • Viral suppression drugs: ***Lamivudine, Adefovir, Tenofovir, combination therapy
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5
Q

Hepatitis B replication cycle

A
  1. rcDNA (relaxed circular DNA, incomplete double stranded) —> cccDNA
  2. cccDNA (covalently closed circular dsDNA) persists in infected cells as mini-chromosome (may randomly integrate into host DNA)
  3. pgRNA (pre-genomic RNA serves as mRNA for protein synthesis)
  4. -ve sense viral DNA from pgRNA by reverse transcriptase (synthesized by virus)
  5. dsDNA from -ve sense viral DNA by reverse transcriptase

***rcDNA —> cccDNA —(persist in cells)—> pgRNA —(reverse transcriptase)—> -ve sense viral DNA —(reverse transcriptase)—> dsDNA
pgRNA —> protein synthesis

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6
Q

Diagnosis of Hepatitis B virus

A
  1. Anti HBs antibody (surface antigen)
  2. Anti HBc / HBe antibody (core antigen, e antigen)
  3. HBV DNA (nucleic acid detection)
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7
Q

***Laboratory diagnosis of acute hepatitis B infection

A

Acute infection: 6 months for symptoms to appear

  1. Hepatitis B infection:
    - S antigen +ve
    - Anti-C +ve
    - HBV DNA +ve
  2. Recent / past / chronic
    - Anti-C IgM +ve —> recent
    - S antigen +ve (6 months) —> chronic
  3. Disease progression / Infectiousness
    - viral DNA quantitative result
    - E antigen +ve —> high viral load (chronic: 6 months: high replication)
    - E antigen -ve / Anti-E +ve —> low viral load (chronic: 6 months: low replication)
  4. Immunity
    - Anti-S +ve
    - Anti-C (+/- Anti-S) —> natural infection induced
    - Anti-S —> vaccine induced (vaccine only contain S antigen)
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8
Q

HBeAg seroconversion

A

HBeAg converted to presence of Anti-E

HBeAg ↓ —> Anti-E ↑ (需要時間: Early convalescent仲未見到Anti-E)

Even though HBsAg is positive (chronic carrier) —> HBeAg low indicates low level of virus replication —> low level of infectivity

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9
Q

Immunity to Hep B

A
  1. Develop anti-S (through vaccination)

2. Cell-mediated immunity (through recovery: CD8 cytotoxic T cell, cytokines)

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10
Q

Viral escape from immune response

A
  1. Viral down regulation of MHC antigen on APC surface —> T cell cannot recognise
  2. Immune tolerance generated by E-antigen
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11
Q

Consequences of Hep B infection

A

Adult:

  1. Virus clearance (>90%) —> complete recovery
  2. Virus persistence —> chronic infection —> long term complication: chronic hepatitis, cirrhosis, cancer

Children (Asymptomatic infection)

  1. ***Virus persistence (>90%)
  2. Virus clearance

Immunocompromised:
1. Virus persistence (100%)

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12
Q

Hepatitis B lead to disease

A

Virus does not kill liver cells directly (***not cytopathic)

  1. Strong cell mediated immunity
    —> destroys infected liver cells
    —> clears virus
    —> acute hepatitis recovery
2. Poor cell mediated immunity
—> virus persists
—> ***chronic infection
—> ***chronic hepatitis B
—> ***chronic liver disease, cirrhosis, primary hepatocellular carcinoma (PHC)

Chronic: Tolerance, Clearance, Latency
—> HBV DNA ↓

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13
Q

Primary Hepatocellular Carcinoma

A

> 80% PHC tumours in HBV carriers have ***viral DNA in tumour cells
—> viral DNA integrated into hosts DNA
—> site of integration for all tumour cells is the same (monoclonal) in a given patient

Pathogenesis:

  1. HBV replication —> integration into host genome —> ***insertional mutagenesis
  2. Repeated death and regeneration?
  3. ***Oncogenes in HBV?
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14
Q

Occupational exposure to HBV and HCV

A
  1. First aid
  2. Report to infection control
  3. Risk assessment
    —> exposure evaluation: source and exposed person evaluation
  4. ***Baseline blood testing for HBV, HCV
  5. ***Post-exposure prophylaxis: HB vaccination / HBIG
    HCV: follow up and early prescription if infected
  6. Follow up lab tests and clinical assessment
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15
Q

Hepatitis C

A
  • Flaviviridae family
  • RNA virus
  • enveloped

Transmission:

  • ***blood products / needles
  • vertical (3-10%)
  • sexual?

High risk groups:

  • IV drug users
  • haemophiliacs

Incubation period:
- 2-3 months

Clinical:
- ***Asymptomatic —> lead to chronic carrier state

Onset:
- Insidious

Fulminant hepatitis:
- very rare

Diagnosis:

  • Serology: Ab takes weeks to develop: ***2 ELISAs
  • Viral RNA: ***PCR Quantitative viral load
  • NO viral culture

Cross-infection:
- Yes

Prevention:
- ***NONE

Treatment:
***Pegylated IFN α2a + α2ab
+ Ribavirin (SE: flu-like symptoms, mood change, dermatological)
+ Protease inhibitor: Telaprevir / Boceprevir

  • Assess viral load at 12 weeks after start of Rx: >2 log (99%) reduction —> predict long term response
  • new antiviral for HCV may trigger reactivation of HBV in co-infected people

Genotypes: —> predict response to antiviral

  • 1: blood transfusion associated —> 50-55% response (need 24-48 week)
  • 2: West Africa —> 75% response at 24 week
  • 6: IV drug user associated —> 48 week Rx
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16
Q

Hepatitis C progression

A
Clearance:
- 30-50% clear within 6 months
- early therapy increases response rate
- clearance depend on:
—> ***T cell response (CD4 + CD8)
—> HLA (Human leukocyte antigen) type
—> IFNλ polymorphism
Persistence:
- 50% persistent
—> mild disease / chronic active hepatitis
—> cirrhosis (50%) / HCC (10%)
—> cirrhosis —> hepatic failure
17
Q

Hepatitis A

A
  • Pico-rna-virus
  • RNA
  • unenveloped
  • ***NO chronic carrier state
  • Disease of adults > children
  • ***Direct Cytopathic effect

Transmission:

  • ***Faecal-oral
  • ***shell fish / oyster
  • seasonal (Dec-May)

High risk groups:

  • uncooked seafood
  • poor hygiene and water

Incubation period:
- 2-6 weeks

Clinical:

  • children 10% symptomatic
  • adult 50% symptomatic

Onset:
- acute

Fulminant hepatitis:
- rare

Sequelae in recovered:
- NO

Diagnosis:

  • **- Serology: IgM antibody
  • NO viral culture

Cross infection:
- NO

Problem with diagnosis:
- Faecal virus titer drop by the time jaundice appears

Prevention:

  • Passive immunisation: normal human immunoglobulin —> rapid onset of immunity but lasts few weeks
  • Active immunisation: HAV antigen vaccine —> stimulate specific immune response in host —> takes weeks / months to develop immunity but long-lasting
18
Q

Hepatitis E

A
  • Orthohepevirus (calici-like)
  • RNA
  • unenveloped
  • HEV 1-4
  • species A-D
  • HEV-A main cause of human infection, rare HEV-C from rats
  • 5 of 8 genotypes infect human (China mainly genotype 4)
  • ***MOST common cause of acute viral hepatitis in HK
  • peak age 45-64
  • ***NO chronic carrier state except immunocompromised
  • convalescent patients shed for weeks

Transmission:

  • Faecal-oral
  • shell fish / oyster
  • seasonal (Feb - May)
  • **- Food / water outbreaks (HEV1/2)
  • **- Undercooked pork (liver, intestine, blood curd) (HEV3/4)
  • vertical
  • (blood transfusion)

High risk groups:

  • uncooked seafood
  • poor hygiene and water

Incubation period:
- 2-8 weeks

Clinical:

  • children: often asymptomatic
  • adult: symptomatic

Onset:
- acute

Fulminant hepatitis:
- severe in immunocompromised

Sequelae in recovered:
- ?

Diagnosis:

  • **- Serology: IgG rising / IgM (Virus can persist in immunocompromised without symptoms and without serological response —> therefore ***molecular detection essential)
  • NO viral culture

Cross-infection:
- no

Prevention:

  • NONE
  • HEV239 vaccine licenced in mainland China

Treatment:
- Ribavirin useful in immunocompromised (together with reducing immunosuppression)

19
Q

Hepatitis D virus

A
  • covered by ***HBV S-antigen
  • incomplete virus
  • need ***co-infection with HBV
  • need help of hepatitis B to supply surface antigen
20
Q

***Comparison of virus

A

HBV:

  • Hepadnavirus DNA enveloped
  • Diagnosis: HBsAg, HBeAg, Anti-C IgM, HBV DNA
  • have ***prevention
  • have ***suppressive treatment (IFN-α + Viral suppression drugs e.g. Lamivudine)

HCV:

  • Flaviviridae RNA enveloped
  • Diagnosis: 2x ELISA for serology, PCR for viral RNA
  • ***NO prevention
  • have ***curative treatment (Pegylated IFN α2a + α2ab + Ribavirin + Protease inhibitor: Telaprevir / Boceprevir)

HAV:

  • Picornavirus RNA unenveloped
  • Diagnosis: IgM
  • have prevention (HAV vaccine)
  • treatment?

HEV:

  • Hepevirus RNA unenveloped
  • Diagnosis: IgM + rising IgG + Molecular detection
  • have prevention (not licensed in HK)
  • have curative treatment (Ribavirin)

HDV: covered by HBsAg