GIS07 Viral Hepatitis, Serological Tests And Immunization Flashcards
Symptoms of hepatitis
- Pain over R hypochondrium (swelling of liver capsule: pain sensitive)
- Jaundice, pale stools, dark urine
- Elevated liver enzymes (Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) —> Parenchymal enzymes)
- Fever
- Loss of appetite, N+V
Aetiology of acute hepatitis
- Viruses
- Hepatitis A, B, C, D, E
- Epstein-Barr virus, Cytomegalovirus, yellow fever virus - Bacteria
- Leptospirosis, Q fever - Parasites
- Toxins + drugs
- Autoimmune disease
Faecal-oral hepatitis vs Blood-borne hepatitis
Faecal-oral transmission (AE):
- Hepatitis A
- Hepatitis E
- Non-A, Non-B
Blood-borne transmission (BCD):
- Hepatitis B
- Hepatitis C
- Hepatitis D
- Non-A, Non-B
Hepatitis B
- 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
Hepatitis B replication cycle
- rcDNA (relaxed circular DNA, incomplete double stranded) —> cccDNA
- cccDNA (covalently closed circular dsDNA) persists in infected cells as mini-chromosome (may randomly integrate into host DNA)
- pgRNA (pre-genomic RNA serves as mRNA for protein synthesis)
- -ve sense viral DNA from pgRNA by reverse transcriptase (synthesized by virus)
- 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
Diagnosis of Hepatitis B virus
- Anti HBs antibody (surface antigen)
- Anti HBc / HBe antibody (core antigen, e antigen)
- HBV DNA (nucleic acid detection)
***Laboratory diagnosis of acute hepatitis B infection
Acute infection: 6 months for symptoms to appear
- Hepatitis B infection:
- S antigen +ve
- Anti-C +ve
- HBV DNA +ve - Recent / past / chronic
- Anti-C IgM +ve —> recent
- S antigen +ve (6 months) —> chronic - 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) - Immunity
- Anti-S +ve
- Anti-C (+/- Anti-S) —> natural infection induced
- Anti-S —> vaccine induced (vaccine only contain S antigen)
HBeAg seroconversion
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
Immunity to Hep B
- Develop anti-S (through vaccination)
2. Cell-mediated immunity (through recovery: CD8 cytotoxic T cell, cytokines)
Viral escape from immune response
- Viral down regulation of MHC antigen on APC surface —> T cell cannot recognise
- Immune tolerance generated by E-antigen
Consequences of Hep B infection
Adult:
- Virus clearance (>90%) —> complete recovery
- Virus persistence —> chronic infection —> long term complication: chronic hepatitis, cirrhosis, cancer
Children (Asymptomatic infection)
- ***Virus persistence (>90%)
- Virus clearance
Immunocompromised:
1. Virus persistence (100%)
Hepatitis B lead to disease
Virus does not kill liver cells directly (***not cytopathic)
- 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 ↓
Primary Hepatocellular Carcinoma
> 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:
- HBV replication —> integration into host genome —> ***insertional mutagenesis
- Repeated death and regeneration?
- ***Oncogenes in HBV?
Occupational exposure to HBV and HCV
- First aid
- Report to infection control
- Risk assessment
—> exposure evaluation: source and exposed person evaluation - ***Baseline blood testing for HBV, HCV
- ***Post-exposure prophylaxis: HB vaccination / HBIG
HCV: follow up and early prescription if infected - Follow up lab tests and clinical assessment
Hepatitis C
- 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
Hepatitis C progression
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
Hepatitis 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
Hepatitis E
- 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)
Hepatitis D virus
- covered by ***HBV S-antigen
- incomplete virus
- need ***co-infection with HBV
- need help of hepatitis B to supply surface antigen
***Comparison of virus
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