Viral Hepatitis and Vaccines (Franco Falcone) Flashcards
What is Hepatitis?
Inflammation of the liver with various causes such as trauma, alcohol abuse. drug induced toxicity or viral infection.
What is Liver Cirrhosis?
An advanced consequence of liver disease progression. It is characterised by fibrosis (tissue replaced with collagenous scars with no function) and regenerative nodules (attempts to repair damaged tissue).
What is a common complication of cirrhosis?
Ascites - fluid retention in the abdominal cavity
Which therapeutic option for liver cirrhosis is available?
Liver transplant is the only option because cirrhosis is irreversible.
How does fibrosis occur?
Fibroblasts produce collagen which leads to formation of scars - they have no function and as a result lead to liver function reduction and associated symptoms.
What is the cause of most hepatitis?
Viruses
What are the types of viruses that cause viral hepatitis?
Hep A, B, C, D, E
HAV HBV HCV HDV HEV
Viral hepatitis can also be caused by other viruses such as Adenovirus, SARS, Ebola, Influenza and others but these viruses mainly cause other symptoms.
What kind of infection do naked H viruses cause?
Naked viruses (HAV, HEV) lead to acute infections, whereas the enveloped viruses (HBV, HCV, HDV) cause persistent and chronic infections and have developed ways of evading immunity.
How does the type of virus (enveloped v naked) affect their transmission?
Naked: oral fecal
Enveloped: blood another body fluids
What are the symptoms of Hepatitis?
Jaundice / Icterus are the most characteristic of hepatitis symptoms.
Yellowing of the skin and eyes due to increased levels of bilirubin in the blood (a hemoglobin breakdown product).
Normally bilirubin is conjugated to form water soluble bilirubin diglucuronide in the healthy liver. In hepatitis this conjugation does not happen.
When is jaundice a less common symptom?
In children 14 y/o or <
Aside from jaundice, what are the other symptoms of hepatitis?
Fatigue Abdominal pain Loss of appetite Nausea and vomiting Dark urine
Is HAV chronic or acute?
Acute; self-limiting
*Can result in fulminant (lightning) hepatitis and death in a small proportion of patients.
What is a benefit of HAV once overcome?
Induces lifelong protection from reinfection
How is HAV spread?
Mainly oral-fecal route; occurs worldwide and increased risk in poorly sanitised places.
What is the structure of HAV like?
Non enveloped, SS(+)RNA
Spherical (pseudo-icosahedrical)
Classified within the picornavirus family.
Baltimore Group IV
VP1,2,3 are the polypeptides on the outer capsid
How long does HBV stay in the body?
1-3 months (acute HBV)
6 months + (chronic HBV is less common)
In 20-25% patients with chronic HBV have progressive liver disease, leading to cirrhosis and around 10% will develop to liver cancer.
How can HBV be transmitted?
Enveloped so transmitted in blood or body fluids
Sexually transmitted
Blood to blood contact (sharing needles or needle stick injuries)
Perinatal transmission from mother to child.
What is the structure of HBV?
Enveloped, icosahedric capsid
A spherical, double-shelled structure, consisting of a lipid envelope containing HBsAg that surrounds an inner nucleocapsid composed of hepatitis B core antigen (HBcAg) complexed with virally encoded polymerase and the viral DNA genome.
HBV is one of few non-retroviral viruses that use reverse transcription as a part of its replication process.
What Baltimore Group is HBV found in?
VII
dsDNA
What is the incidence of HCV?
UK: 216,000 chronic hep C patients
87% are current or past injected drug users.
What are the symptoms of HCV?
In most cases, hepatitis C causes no noticeable symptoms until the liver has been significantly damaged
Chronic liver disease progression in 70-75% of patient with Hep C - can lead to liver failure and/or cancer.
Is there a vaccine for Hep C?
No
How is HCV transmitted?
Enveloped so transmitted via blood or bodily fluids.
Usually transmitted blood-blood due to high concentrtion in the blood
Semen, vaginal fluid and saliva to a much lesser extent.
What is the structure of HCV?
Enveloped, spherical, mature virions contain two virus-encoded membrane proteins (E1 and E2) in addition to capsid protein.
Baltimore Group IV SS(+)RNA
How can Hep C vary between places?
There are 11 genotypes of Hep C
Genotypes 1,2,3 most widespread across Europe.
Genotype 4 in Africa
Genotype dictates the type of treatment needed.
What are the treatment options for Hep C?
Current Tx: Combination of Ribavirin (oral nucleoside analogue) and Pegylated IFN-alpha (cytokine peptide).
Treatment for 6-12 months
Cure rate 20-40% only.
What are the cautions with Ribavirin use?
Teratogenic - should not be used in pregnant women
How does genotype affect treatment?
Ribavirin combined with pegylated INF-alpha Tx
3x more effective in genotype 2 or 3 than in genotype 1
What are the newer drugs available for Hep C treatment?
Boceprevir and Telaprevir (target HCV protease) Used for Genotype 1
What type of virus is Hep D?
A defective virus / ‘satellite’ virus; it cannot exist on its own.
What is needed for Hep D infection?
Co-infection with Hep B which provides the antigens needed for cell host cell attachment and infection.
Once inside the cell HBV can replicate independently.
What is the structure of HDV?
Enveloped, spherical
Membrane proteins originate from HBV helper virus.
What Baltimore Group is HDV from?
V
What is the significance of HDV?
The hepatitis delta virus relies on co-infection withHBV because it uses HBsAG as its own virion coat.
Chronic HBV can lead to liver cancer
Which Hepatitis Viruses can be vaccinated against?
Hep A and B
What is the difference between active and passive vaccination?
Passive immunisation is the injection of pathogen-specific pooled human immunoglobulin (antibodies). Passive vaccination does not confer life long protection.
What are live attenuated viruses?
Better. Viruses are grown in cultures and repeatedly passaged through rounds of culture. Viruses with low virulence are selected and these attenuated strains are reproduced in large quantities for vaccination. Immune response (similar to natural response) without causing full illness. Live vaccines avoided in immunocompromised oncology patients.
How do inactivated vaccines cause protection?
Viruses are cultured and inactivated with formaldehyde. These vaccines have fewer side effects that live attenuated by the immune response elicited is less vigorous.
What are subunit vaccines?
The safest method of vaccination
Surface antigens are produced by recombinant DNA technologies. The recombinant proteins can be given alone or with up to 20 other proteins.
The pathogen is not present so no risk to patients but the immune response is still evoked.
HBV and Influenza vaccine.
What kind of vaccine are flu vaccines / HBV vaccines?
Subunit vaccines.
How can we vaccinate against HAV?
There is only one HAV serotype (but atleast 7 different genotypes)
One strain vaccine can protect against all genotypes.
Vaccine consists of inactivated whole viruses propagated in MRC-5 human lung fibroblast cell line.
What three types of vaccine protect against HAV?
Monovalent vaccine which provides protection against HAV
Combined HAV and HBV vaccine
Combined HAV and typhoid fever vaccine
What kind of vaccination can be given against HBV?
Subunit vaccine consisting of HBsAg adsorbed onto aluminium hydroxide adjuvant
Prepared from yeast using recombinant DNA technology.
Combined HAV and HBV vaccine
Usually 3 doses with or without a booster
When can HBV vaccine be given as Tx?
Vaccine is highly effective is given shortly after exposure e.g. needle stick injury
