Hepatitis Flashcards
What are the two types of viral hepatitis that can be transmitted via the fecal oral route?
• why does this make sense based on their structure?
Hepatitis A and E are both non-eveloped so they don’t need to say moist while B and C both have envelopes so they can only be transmitted in fluids.
*Hepatitis D is non-enveloped, but is dependent on co-infection or superinfection with hepatitis B which IS enveloped
What is the only way that you can get infected with hepatitis D?
Co-infection with hepatitis B
What two types of Hepatitis can be chronic?
Hepatitis C - most often chronic
Hepatitis B - rarely chronic except in young children
What is the only DNA hepatitis virus?
Hep B (note that EBV and CMV can cause hepatitis, but they are not one of the classic hepatitis viruses)
**Remember that any case of chronic hepatitis puts you at an increased risk for hepatocellular carcinoma
HAV:
• Virus Family
• Virus Genus
• Structure
Family: Picornaviridae
Genus: Enterovirus
Structure: Nonenveloped icosahedral capsid, 7kb ssRNA
HEV:
•Virus Family
• Virus Genus
• Structure
Family: Calciviridae
Genus: Hepevirus
Structure: Noneveloped icosahedral capsid, 7.5 kb ssRNA
Why is HAV a good disease target for eradication?
- One Serotype
* Human Reservoir
What are the reservoirs for HEV?
• where is it most prevalent?
Reserviors:
• Swine or other animal reserviors
Prevalence:
• Not common in the US
What complication of HEV is VERY important to know?
There is a 20% fatality in pregnant women
How long is the incubation period for HAV?
• When are patients contagious?
• when in the course of life is disease most common?
• Most common symptoms?
How Long:
• 2-4 wks Post Exposure
This typically occurs in EARLY CHILDHOOD and is most commonly ASYMPTOMATIC
T or F: HAV accounts for a significant amount of US acute hepatitis?
True, 1/3 of all Acute hepatitis in the US is due to HAV
How long is the symptomatic period of Hep A?
• what are they symptoms?
4-10 weeks
Symptoms:
• Vomiting, anorexia, malaise, fever, headache, jaundice (aversion to cigarettes)
T or F: 1/3 of the US population has had HCV.
False, 1/3 of the US population has had HAV not HCV
How do outbreaks of HAV typically happen?
Salad bars on cruise ships and Raw Shellfish
During what weeks after initial infection would you expect to have a high ALT as a result of HAV?
• what about anti-HAV IgM?
ALT begins to elevates at wk 4
Peaks at week 7
Decrease to normal at week 10
• anti-HAV IgM parallels ALT, but doesn’t max until week 8 then falls back down by week 12
What happens to IgG levels in HAV infection?
IgG starts kicking in around week 4 and peaks around week 12
Who is at the greatest risk of contracting HAV?
• on a normal basis?
• During outbreaks?
- Household or sexual contacts
- Travelers to endemic areas
- Inhabitants of American Indian Reservations
During outbreaks:
• Diners, Day care center workers, Gay men, Injecting Drug Users (REMEMBER ONLY DURING OUTBREAKS)
Is HAV considered an STD?
NO, but it is fecal oral and sex opens the door to this type of transmission
How is the diagnosis of HAV made?
- Presumptive diagnosis on the basis of appearance
* Detection of anti-HAV IgM
If you have a close contact with HAV, how can you avoid getting the disease?
Passive immunization with gamma globulin
What vaccines are available for HAV and for whom?
- Inactivated Vaccine - 2 years or older
- Combination HAV/HBV vaccine - (just the inactivated vaccine + HBV vaccine) => for children 18 years or older
***Travelers to endemic areas should definitely get the vaccine
What prevented the HAV outbreak in memphis in the 90s from becoming widespread?
• the HAV vaccine was used here to prevent new disease
HBV
• Virus Family
• Structure
Family:
Hepadnavirus
Structure:
EVELOPED, PARTIALLY dsDNA CIRCULAR genome - DNA pols just stops part way through the replication of the 2nd strand
What are the 5 MAJOR proteins of HBV?
- DNA pols (REVERSE transcriptase)
- HBsAg (surface antigen, attachment protein)
- HBcAg (core antigen, capsid protein)
- HBeAg (derivative of HBcAg, important serologic marker)
- X antigen (influences gene expression)
What feature(s) of HBV allow use to simultaneously treat HBV and HIV?
• DNA pols is also reverse transcriptase - allows us to simultaneously treat HIV and HBV
What is the role of the X antigen in altering gene expression?
X antigen - allows the HBV genome to be effectively expressed in liver cells
What are the steps in infection of a cell with HBV?
- Viral envelope fuses with the cell to enter
- Uncoats and the 1st thing that occurs is the *VIRAL pols * that is associated with the genome when it comes in goes ahead and completes full length synthesis so that you get a dsDNA genome
- DNA goes into the nucleus and gets transcribed to RNA with HUMAN RNA pols (dna dependent rna pols)
- RNA exits the nucleus and the Hep B DNA pols uses its REVERSE TRANSCRIPTASE capacity to convert RNA into DNA
This is the opposite of what HIV does
What countries are you most likely to acquire HBV in?
- China
* Sub-Saharan Africa
How is HBV transmitted?
Transmission:
• Sexual - blood, semen, and vaginal secretions
• Parenteral - IV drug use
• PERINATAL delivery
Does the baby of a mom with HBV automatically have HBV?
• what should you do when they are born?
NO - HBV is acquired during delivery
Start treating them for HBV when they are born
Compare the infectivity or HBV and HAV.
HAV is much more infective than HBV
Compare the amount of time it takes for ALT to become elevated in HAV to HBV.
HBV has an ALT that doesn’t start to elevate until 8 weeks and doesn’t max until week 16 (goes back to baseline about week 28)
Compare this to HAV that starts to elevate at week 4 and maxes out at week 7
How long is the incubation period for HBV?
• symptomatic period?
8 weeks after initial infection
10-36 weeks after initial infection
If HBV has not resolved in _____ months its considered chronic.
• what is typically the first sign of chronicity?
HBV that has not resolved for 6 months is considered chronic
Chronicity is usually not noticed until patients present with cirrhosis or HCC appears
Which HBV marker tells you that you’re acutely infected?
HBsAg (the actual antigen can only be elevated in someone with actual virus in them)
Which HBV marker is an ID of persons who have had HBV infection or received the vaccine?
Anti-HBs (antibody to the surface antigen can be in people who have recently received the vaccine)
Which HBV marker is an indicator of active infection?
HbeAg (this is the ID of people who are at HIGH RISK OF TRANSMITTING THE VIRUS)
Which HBV marker is the ID of people who have HBsAg but have only a low risk of transmission?
Anti-HBe - Anti-HBe + Anti-HBsAg => low risk of transmission
What is the ID HBV marker of persons with a past infection?
Anti-HBc (core antibody will only be elevated in people that ACUTALLY get infected)
What does it mean if someone has a high IgM Anti-HBc?
IgM anti-core antibody is only elevated in people with ACUTE infection
What two actual virus particles appear in the serum after the Hep B surface antigen?
E antigen and HB DNA are the next things to appear in the serum
How long before IgM appears in a Hep B infection
Typically starts appearing 8 wks after infection and doesn’t peak until about week 20
What serologic markers of the Hep B virus would you expect to see in someone who has been vaccinated?
IgG for Surface Antigen ONLY
What state of disease is someone in if they have core and surface antigens as the only markers in their serum for Hep B infection?
These markers indicate a resolved acute infection
Hepatitis D
• Structure
Eveloped ss RNA virus (very small)
Compare symptoms and risk of chronic infection in Co-infection of HBV and HDV to superinfection of HBV with HDV.
Coinfection:
• WORSE bout with HBV than with HBV alone, but your risk of becoming chronic is the SAME
Superinfection:
• This is a person who has HBV but has had no infection for years and shows back up with Worsening symptoms
• These people are at a higher risk of CHRONIC HBV infection
Why do we screen people born between 1945 and 1965 for HCV?
- Before 1989 we didn’t know about HCV so blood supplies weren’t screened
- Most people who received blood before 1989 were in this age group so its important to screen
HCV
• Family
• Structure
Family:
•Hepacivirus
Structure:
• Enveloped icosahedral capsid
• 9.4 kb ssRNA POSITIVE sense genome
What is unique about the enveloping of HCV?
• what is the importance of this envelope in the host response to infection?
HCV:
• has TWO envelope proteins E1 and E2
• E2 is immunodominant and mutates A LOT so even the same infection morphs over time creating QUASI-SPECIES allowing the infection to persist by evading host response
What are the two most common subgroups of HCV in the US?
HCV 1a and 1b are the most common in the US
T or F: the US prison population has a much higher risk of HCV compared to the NL US population.
True, US prison population has rates of 16-41% while the general population has rates of ~2%
What are the Risk Factors for acquiring Hep C infection?
- Born Between 1945 and 1965
- Illicit (IV) drug use
- Perinatal infection at birth
Compare acute infection of HBV to acute infection with HCV.
Acute infections with HCV are generally much milder than acute infections with HBV
Compare the pattern of ALT overtime in a chronic HCV to HBV.
HCV has up and down pattern of ALT because of Re-infection as the result of Quasi-Species
What is the actual cause of liver damage in ALL Hepatitis infections?
- OUR OWN IMMUNE RESPONSE VIA CYTOTOXIC T CELLS IS WHAT CAUSES THE PROBLEMS
- Hepatitis viruses are not cytolytic
What percentage of chronic hepatitis cases are due to HCV?
• HBV?
HCV:
• Accounts for 40% of all cases of Chronic Hepatitis
HBV:
• Accounts for 20% of all cases of Chronic Hepatitis
***5% of HBV cases are HDV positive
How does your chance of developing a CHRONIC HBV infection change with the age at which you were infected?
- Less than 1 y/o then 90% Chronicity
- 1-5: 30% Chronicity
- Greater than 5: 2% Chronicity
What are some extrahepatic disease that you can develop as a result of HBV?
- Polyarteritis nodosum (erythema nodosum, and arthralgia)
- Membranous Glomerular nephritis
- Membranoproliferative Glomerular Nephritis
What are the 3 stages of Hep B infection?
• when do we become symptomatic?
3 stages:
1. Immune Tolerance phase - virus proliferates and is unrecognized by the immune system, there is NO CELL DAMAGE, and NO SYMPTOMS
- Immune Clearance phase - virus proliferates and the immune system attacks the cells.
- Residual phase
What percentage of patients with HCV acute infection will become chronic?
85% of these patients will become chronic
***Why does it take so long for cancer to develop in Chronic Hepatitis patients?
The hepatitis viruses do NOT integrate into the host cell DNA, therefore they do not cause disease as quickly as viruses like HPV
**The problem in Hepatocellular Carcinoma is that Liver Cells are not made to regenerate effectively so when they do they are more prone to error
What vaccine should you suggest in patients with chronic HBV or HCV infections?
• what other dietary recommendation should you make?
HAV vaccine should be given to these patients because they are at increased risk of Acute Liver Failure if they acquire the infection
Patients SHOULD NOT DRINK EtOH
What antigens and antibodies can be detected for HCV via ELISA?
• what else do you need to find when you get an HCV infection?
anti-HCV antibodies
HCV RNA
When is Hep B Ig used?
Exposed Individuals
• Newborns
• Prophylactically for Travelers
For which types of Hepatitis is there a vaccine available?
HAV and HBV
How do we now prevent most HCV infections?
Screen the Blood supply
What is unique about the treatment of HCV?
IT IS A CHRONIC DISEASE THAT WE CAN CURE
What determines the specific treatment you will use for HCV?
The GENOTYPE of the virus
Enecavir works by binding the Hep B DNA pols and seizing it up
Tenofovir works by preventing the addition of another nucleotide in Hep B infection
T or F: Adults over 40 are at higher risk of HAV
True, so are people with existing liver disease so make sure they get Hepatitis vaccines for the type of hepatitis that they do not have
