Viral Hepatitis Flashcards
What is the virus structure?
• are not able to replicate by themselves but require host cells and its cellular biochemical machinery to generate progeny • consist of DNA or RNA enclosed within a virus-encoded protein coat (nucleocapsid) and (sometimes) an outer-most host cell membrane-derived envelope • attach to host cell using receptorbinding proteins targeting host cell surface molecules that also serve as virus-specific receptors
What are the clinical symptoms of hepatitis?
- yellowing of skin and eyes (jaundice- increase bilirubin)
- dark urine
- clay-coloured stool
- nausea and vomiting
- loss of appetite
- fever
- abdominal pain
- weakness
What are the biochemical and serological tests for hepatitis?
• biochemical blood tests for hepatitis = liver enzymes (ALT, AST, ALP, GGT) = other liver proteins (e.g. albumin, prothrombin) = bilirubin (direct, indirect) • serological and molecular tests for viral hepatitis s - Enzyme Immunosorbent Assays (EIA) = Viral antigen = Anti-viral antibody - Molecular assays = PCR = Viral load - Sequencing = Genotype = Antiviral resistance • liver biopsy
Which hepatitis viruses are similar?
A and E (faecal, oral transmission)
B, C and D (parenteral, sexual)
Describe Hepatitis A Virus
• non-enveloped ss+ve RNA picornavirus
• at least 6 major genotypes, I-VI (type I is prevalent worldwide)
• incubation time is 10-50 days (avg 25-30 days)
• primarily children and young adults
• no seasonality (peaks may be seen in autumn)
• faecal-oral transmission
• abrupt onset, commonly with pyrexia
• resolves spontaneously (without chronicity – ie, no carrier
state) followed by life-long immunity
• fatality rate <0.5% in icteric cases (age dependent)
• inactivated virus vaccine (and immunoglobulin*) available
• treatment: supportive
Describe HAV transmission
- Sewage-contaminated water
- Shellfish filter off virus particles while feeding
- Shellfish harvested; eaten raw or partially cooked
- Virus ingested
What is the HAV Course of Infection?
- anti-HAV IgM in blood • IgM antibody to HAV • indicates recent HAV infection • persist for up to 4-6 months post infection - HAV RNA in blood • present at the onset of symptoms/signs - anti-HAV IgG in blood • IgG antibody to HAV • indicates HAV infection (or vaccine response) • detectable by onset of symptoms/signs • persists for life
Describe Viral Hepatitis Prevalence
A= Sub Saharan Africa, India, SE Asia B= Sub Saharan Africa, SE Asia, Russia C= anywhere, European and north American D= Europe, South America, Sub Saharan Africa E= higher distribution, E Europe, South France
What is the HAV outcome?
Children vs Adults =Subclinical infection= C 80-95%/ A 10-25% =Icteric disease= C 5-20%/ A 75-90% =Complete recovery= >98% both -No chronic disease =Fatality rate= C 0.1%/ A 0.3-2.1%
Describe Hepatitis B Virus
• Enveloped partially dsDNA hepadnavirus
• At least 8 main genotypes, A-H (type
A is prevalent in Europe)
• Incubation time is 40-180 days (avg 60-90 days)
• Primarily babies and young adults
• No seasonality
• Parenteral, vertical, sexual transmission (close contact)
• Insidious onset, sometimes apyrexial
• Virus remains in hepatocytes for life and may re-active under
immunosuppression (anti-HBcAb IgM may become detectable again)
• Chronic infection* (carrier state) develops in 5-10% of adults (but >95% of
neonates) and is associated with hepatocellular cancer
• Up to 2% fatality rate in icteric cases- liver failure
Describe HBV treatment
Recombinant HBV surface antigen vaccine (and immunoglobulin**) available
• Treatment (for chronic infection): Interferon alpha OR antivirals (eg, tenofovir,
entecavir); HBsAg seroconversion will occur in a small proportion of cases
treated with interferon alpha, but is even less likely to occur with antivirals;
however, antivirals are very effective in suppressing virus replication
(* Hepatitis B surface antigen-positive >6 months; ** Limited use)
Describe HBV structure
- Virion Dane particle
- Surface antigen= protein on envelope
- HB particles
Describe HBV Nomenclature
Hepatitis-B Surface Antigen (HBsAg)
• Found in HBV envelope
• Indicates active HBV infection
• Found in serum during acute and chronic (carrier state) infection
• Anti-HBsAg (antibody to HBsAg)
= Indicates past HBV infection or immune response to HBV vaccine
or passive antibody transferred following administration of HBV Ig
(HBIG)
Hepatitis-B Core Antigen (HBcAg) • Part of the HBV nucleocapsid • Anti-HBcAg IgM (IgM antibody to HBcAg) = Indicates recent HBV infection = Persists for 4-6 months post infection • Anti-HBcAg IgG (IgG antibody to HBcAg) = Indicates recent or past infection with HBV = Detectable by onset of acute symptoms and persists for life
Hepatitis-B E Antigen (HBeAg) • Associated with HBV nucleocapsid • Indicates active HBV infection • Anti-HBeAg (antibody to HBeAg) = Indicates HBV seroconversion
Describe HBV acute infection
Anti-HBc
-1 month= onset
Antibodies take time to develop-Surface antigen eliminated from blood when antibodies take over
E antigen= high viral load
Describe HBV chronic infection
-HBsAg
Surface antigen persists
Surface antibodies neutralise
HBsAg HBV Serological Profile
Incubation period
Acute HBV
Carrier (high infectivity)
Carrier (low infectivity)
Anti-HBsAg HBV Serological Profile
Convalescence
Recovery
Vaccination
HBIG
Anti-HBcAg IgM HBV Serological Profile
Acute HBV
Convalescence (-/+)
Anti-HBcAg IgG HBV Serological Profile
Acute HBV
Convalescence
Recovery
Carrier (high and low infectivity)
HBeAg HBV Serological Profile
Incubation period
Acute HBV
Carrier (high infectivity)
Anti-HBeAg HBV Serological Profile
Convalescence
Recovery (+/-)
Carrier (low infectivity)
HBV Prevalence in Europe, N America and Australia
HBsAg= 0.2-0.5%
Anti-HBs= 4-6%
Neonatal infection= Rare
Childhood infection= Rare
HBV Prevalence in East Europe, Med, USSR, South America, SW Asia
HBsAg= 2-7%
Anti-HBs= 20-55%
Neonatal infection= Frequent
Childhood infection= Frequent
HBV Prevalence in SE Asia, China, Africa
HBsAg= 8-20%
Anti-HBs= 70-95%
Neonatal infection= Very frequent
Childhood infection= Very frequent
Describe vertical transmission of HBV in endemic regions (Asia, Africa)
- New-borns, infants
- 5% recovery from acute infection
- 95% progression to chronic infection
- 10-20% chronic carriers
Describe contact transmission of HBV in endemic regions
- Young children
- 20% recovery from acute infection
- 80% progression to chronic infection
- 10-20% chronic carriers
Describe parenteral and sexual transmission of HBV
- Teenagers, adults
- 90-95% recovery from acute infection
- 5-10% progression to chronic infection
- 0.5% chronic carriers
Describe Hepatitis C Virus
Enveloped ss+ve RNA flavivirus
• At least 6 main genotypes, 1-6 (types 1 and 2 are prevalent in Europe)
• Incubation time is 15-160 days (avg 50 days)
• Primarily adults
• No seasonality
• Parenteral transmission (?sexual route)
• Acute phase very often completely asymptomatic
• Chronic infection established in 70-90% of cases
• Chronic infection (carrier state) is associated with hepatocellular cancer
• Up to 1% fatality rate in icteric cases
Describe HCV treatment
• No vaccine available
• Treatment: Interferon alpha together with ribavirin OR direct-acting
antivirals (DAAs) such as protease inhibitors (eg, boceprevir, telaprevir)
and/or polymerase inhibitors (sofosbuvir)
• Increasingly, with the advent of DAAs, HCV is fast becoming a largely
curable (>90% [genotype independent]) infection
What are the novel HCV antiviral drugs?
-Targeting translation and polyprotein processing = Protease inhibitors =NS5A --Targeting RNA replication =NNPI =NS5B polymerase inhibitors
Describe HCV course of infection
Anti-HCV Antibodies • Antibodies to HCV • Indicates recent and/or past HCV infection • Take up to 3 months to develop HCV Antigen • Reflects viraemia (active infection) HCV PCR • Determines viraemia and, thus, whether infection is an active one (which requires treatment; success depends on genotype) IL28B genotype (single nucleotide polymorphism) • Helped to determine susceptibility to antiviral therapy, but is of reduced/limited use now
What is Viraemia?
Virus in blood = active infection; virus is actively replicating
Describe Hepatitis D virus
enveloped circular ss-ve RNA
• at least 3 major genotypes, I-III (type I is most prevalent worldwide)
• similar to HBV, envelope contains HBsAg
• defective virus that needs HBV for
replication
• co-infection with HBV:
• severe acute disease
• low risk of chronicity
• super-infection on chronic HBV infection:
• chronic HDV infection
• high risk of severe chronic liver disease
• HBV vaccination provides indirect protection against HDV
Describe Hepatitis E Virus
• non-enveloped ss+ve RNA hepevirus
• 7 genotypes, 1-4 in human [type 1 and
2
cause outbreaks in humans; type 3 and 4
are also found in animals (incl swine,
deer); type
3 is found worldwide]
• faecal-oral transmission
• incubation time 15-60 days (avg 40 days)
• overall fatality rate is 1%-3% (but 15%-
25% in pregnant women in outbreaks
[HEV genotype 1])
• no chronicity identified (except in the
immunocompromised)
• probably endemic in Europe but underdiagnosed
• no vaccine (HEV genotype 1 vaccine
available in China)
• treatment: Supportive; ribavirin can be
used to treat chronic infection
What are other viral causes of Hepatitis?
- Non-A/E hepatitis
- Epstein-Barr virus (EBV)
- Cytomegalovirus (CMV)
- Herpes simplex virus type 1/2 (HSV-1/2)
- Rubella virus
- Enteroviruses
- Yellow fever virus
