Hepatitis virus Flashcards
Why is the hepatitis virus historically important?
One of the only conditions that has lead to complete remission following therapy
What are the different types of Hepatitis virus?
A, B, C
How are the different Hepatitis viruses classified?
How they transmit
Type of nucleic acid
Hepatitis viruses are genetically linked
TRUE or FALSE
FALSE
Is the pathogenesis of hepatitis cytolytic?
No
It does not cause coughs or runny noses
Depends on the immune response to cause cell damage
How is HBA transmitted?
Water
How is HBV transmitted?
Blood
Mother to child - commonest
Sex
How is HCV transmitted?
Blood
Rarely transmitted through sex or from mother to child
Snorting drugs
Injections
Blood products
What is the pathogenesis of HBV?
Chronic
What is the pathogenesis of HCV?
Chronic
What is the pathogenesis HAV?
Self-limiting
What type of nucleic acid is found in HBV?
DNA
What type of nucleic acid is found in HCV?
RNA
What is the consequence of the chronicity of HBV and HCV?
Responsible for the immune mediated liver damage that leads to fibrosis and cancer
What is the consequence of the self-limiting property of HAV?
Individuals clear the virus, recover and have lasting immunity
How was hepatitis B discovered?
Electromyography
How was hepatitis A discovered?
Culture
How was hepatitis C discovered?
Blood from chimpances with non-Anon-B hepatitis was obtained
The total RNA and DNA was extracted
Genes were used to make complementary DNA (cDNA)
These were then inserted into eukaryotic bacteria, which used their replication machinery to clone the sequences
Antibodies from NANBH patients were obtained from the plasma
Scientists identified the sequences of DNA these antibodies bound to
What differentiates cDNA from normal DNA?
It has been modified by post-transcriptional modification to remove the introns
Only codes the exons
Contains a poly-A tail
What gene was identified to belong to the HCV?
5-1-1 clone
What type of nucleic acid is found in HCV?
Positively-stranded RNA
What year was the HCV genome discovered?
1993
What does the HCV genome code for?
Only codes for structural proteins
Including core and envelope proteins
And non-structural proteins
RNA polymerase, replication complex and serine proteases
What is a good target to knock out viral function?
RNA polymerase
What percentage of acute hepatitis viruses become chronic?
80%
From the chronic infections, what percentage is associated with which level of fibrosis?
30% develop mild fibrosis
30% develop moderate fibrosis
20% develop severe fibrosis
What happens to the patients with chronic hepatitis that develop severe fibrosis?
They develop cirrhosis, which subsequently leads to cancer and death
Some improve their condition and develop moderate fibrosis with normal life expectancies
What happens to the patients with moderate and mild fibrosis?
They go on to have normal life expectancies
Some people with moderate fibrosis might develop severe fibrosis
What happens to the 20% of patients with acute hepatitis which do not develop chronic infections?
Resolution
Which factors affect the progression of cirrhosis?
Alcohol
Weight
Gender
Age
Onset of disease
How many people in the world are infected with Hepatitis C?
160 million people
What percentage of Hepatitis cases happen in Europe?
0.4-3.5%
Where are incidences of hepatitis higher?
In cities
How many major types of HCV exist?
6
How are the 6 different types of HCV differentiated?
Genetically
Why is it important to differentiate between the 6 different families of HCV?
Drugs might affect the different families in different ways
Active sites are differently shaped
How are the 6 different HCV phylotypes arranged throughout the world?
There are clusters of different virus phylotypes throughout the world
Prevalence depends on the behaviours typical for said area
Areas with more injections and higher rates of intravenous drug users have higher rates
What are the two main strategies of treating HCV?
Boosting host immunity
Direct antiviral agents
Examples of molecules boosting host immunity
Interpheron alpha
Examples of direct antiviral agents
Protease inhibitors
Polymerase inhibitors
Replication complex inhibitors
What was the outcome of boosting host immunity when first implemented to treat HCV?
Disappointing
Only a 5% success rate
Lots of side-effects
What was outcome of antiviral agents in HCV?
Higher success rates than boosting host immunity
What was the most successful treatment of HCV?
Combination therapy
Boost the host immunity and direct antiviral agents
What drug changed HCV infections?
Polymerase inhibitors
Have a 100% success rate
Why does HCV not develop resistance to polymerase inhibitors?
Because the selection pressure is so high that the mutation needed to gain resistance would render the virus non-viable
Characteristics of the HBV genome
Complex genome
Genes overlap since there are no stop codons separating the genes
Genes are encoded in one continuous cycle
How does the genome of the HBV affect its function?
Functions of the proteins encoded for by the hepatitis B overlap, much like the genome
How does HBV evade the immune system?
Some proteins encoded for by the genome help the virus evade the immune system
Hepatitis B can reduce the expression of virus proteins once the body detects these in the immune system
Hepatitis B forms reservoirs in its host by making circular complementary DNA strands in the nucleus, making it impossible for the host immunity to access these virus particles
How does Hepatitis B cause cancer?
Incorporates random sequences of DNA into the genome
Affects the function of tumour suppression genes
What two markers are used to assess patients with chronic HBV infection?
HBV markers - HBsAg, anti-HBe, HBV DNA
Liver disease markers - biochemical parameters (ALT). fibrosis markers (non-invasive markers of fibrosis, liver biopsies)
Which parameters are used to assess Hepatitis B infection?
- Active or carrier state
2. e antigen positive or negative
What are the three phases of chronic HBV infection with time?
HBeAg+ chronic hepatitis
Inactive-carrier state
HBeAg- chronic hepatitis
Describe the HBeAg+ stage of chronic HBV progression
There is immune tolerance to the virus
Antigens for HBV are high
Serum ALT levels are low since there is not a severe immune response mounted
As the immune system reacts to the virus, the ALT levels rise as the hepatocytes are attacked by the immune system, as the virus injects its DNA into these cells
Viral load decreases as a response
Describe the inactive-carrier stage of HBV progression
As the initial infection is cleared since the viral load is kept low, the cirrhosis goes back to normal
Not present in all patients
Describe the HBeAg- stage of HBV progression
The immune reaction is re-established following immunosuppression that increases viral load
The serum is negative for Hepatitis B antigens due to mutations to the viral genome
The serum is positive for Hepatitis B antibodies
How many people die worldwide from HBV?
500 000
Why is HBV deadly?
Can lead to cirrhosis in chronic infection
This is deadly if severe, since it leads to conditions like liver failure following decompensation and liver cancer
How many people are infected with HBV worldwide per year?
350 million
How many people in Europe are infected with HBV?
7000 - 8000 cases
What is the main goal for therapy of HBV?
Improve the quality of life and survival of patients by preventing the progression of the disease to cirrhosis, end-stage liver disease and death
Therapies must cause a sustained suppression of HBV replication and reduce the histological activity of chronic hepatitis B
What is a factor that directly correlates with survival in HBV patients?
Prognosis of a HBV patient is related to the viral load
The higher the HBV DNA level, the increased severity of cirrhosis and cancer present in patients
What are the three mechanisms by which HBV causes cancer?
Fibrosis and cirrhosis
DNA integration
Oncogenic proteins
