14 - Hepatitis Flashcards
What are the main causes of acute viral hepatitis in the USA (as of 2013)? What about Chronic?
Acute: Hep C most, then Hep B, smallest amount of Hep A.
Chronic: HepC most chronic in the US followed by HepB (in other places HepB is more chronic). HepA is not chronic.
What type of virus causes HepA? How many serotypes are there, and how is it spread?
RNA picornavirus.
Single serotype, only infects human.
Fecal-oral; spread through contaminated food, water, raw shellfish, and poor hygiene. Most commonly by food handlers, daycare workers, and children.
What is the incubation period of HepA? What does the virus cause?
~4 wks (2-6 wk range).
Acute disease and asymptomatic disease.
Symptomatic causes jaundice: 70-8-% adults and 10% children (these percentages are true for all symptoms of Hep)
What is the fatality associated with HepA? Can it become chronic? What is the immunity?
Fatality: overall 0.3%, >50 years: 1.8%
No chronicity, so you will never find it in a person for more than 6 mo (although it may kill you in that six months - rarely)
Protective Ab develop in response to infection confers lifelong immunity (if you survive the 6 mo, you are immune forever)
What occurs when HepA enters the body?
Enters via oral acquisition, crosses the intestines to enter the blood.
Some is released into stool.
What body fluids have the highest concentration of HepA virus?
Feces (because its fecal-oral), then serum, then saliva.
Urine does NOT have any.
What are the most common sources of HepA virus in the US?
- Personal contact
- Day care center
- Foreign travel
- Drug use
- Outbreak
What are clinical symptoms of viral hepatitis A?
Fever Fatigue Nausea Loss of appetitite Abd. pain - RUQ (liver) Dark urine (bilirubinuria-bilirubin leaking into the urine) Jaundice (seen in eyes first)
Not many symptoms in children.
Describe the time it takes for HAV-specific immunoglobulins to appear after ingestion of virus?
- virus in feces (but we never look for virus in feces the clinical setting)
- HAV-IgM: tells you you have acute HepA
- HAV-IgG: means you were exposed and recovered and are now immune or you were vaccinated
How do you diagnose HepA? What does each tell you?
HepA Ab
HepA IgM = acute (<6 mo) ie you currently have it
HepA IgG = previous exposure (>6 months) and now immune or vaccinated ie you no longer have it
-protective antibody
Who should get the HepA vaccine? When should they get it?
All children at age 1, people working in or traveling to areas with high incidence (mexico), people with chronic liver disease(alcoholic cirrhosis), or working with HAV.
To doses, six months apart.
If you don’t have time for the 2 shots 6 months apart, how do you prevent HepA pre-exposure? What about post exposure?
Pre-exposure: immune globulin to travelers to int-high HAV endemic regions.
Post exposure (within 14 days): immune globulin routine to do household and intimate contact.
What type of virus is Hep E? What is the incubation time and how is it spread?
RNA calicivirus.
Fecal-oral, contamination drinking water, minimal person-person, recent travel to endemic area.
Over 40 day incubation.
E is very similar to A.
What is the case fatality of HepE? Can it become chronic? Where is it most common geographically?
Overall: 1-3%
Pregnant women: 15-45% - pregnant women have a MUCH HIGHER risk of mortality with HepE than A
No chronicity
Central America, north Africa, middle east, and china.
What is the typical serological course of hep E?
Some virus will be seen in stool first
ALT is the most common to go up in the serum with a HepE infection.
IgG anti-HEV and IgM anti-HEV are present as well
There is no vaccine so if someone has IgG that means that they’ve had the disease
How would you diagnose hep E?
Hep E Ab
Hep E IgM = acute (<6 mo)
Hep E IgG = previous exposure (>6 mo) and now immune
-protective Ab (this is in contrast to HIV where having the protective antibody does NOT mean you’re protected)
What type of virus is HepB? What are some examples? What are the different genotypes? What genotype is most associated with cancer?
DNA Hepadnavirus.
Woodchucks, ground squirrel, duck hepatitis virus (remember HepA and HepE were not found in animals)
Genotypes A-H: C is the one most associated with cancer
What is the structure of Hep B?
It’s mostly dsDNA
Dane particles are found in serum: made of hepB antigen only, there’s no DNA
Describe how Hep B viral particles infect a cell and spread? What happens in this process if you’re immunized?
If you are immunized the virus
can’t attach to the liver.
- after attaching it uncoats
- enters nucleus
- mRNA completed
- goes into cytoplasm
- reverse transcription occurs
- then you make a DNA template and it is coated
- Then the active virus is released (sometimes the coating material is released on its own – this is what is given with antibodies (remember it doesn’t have theDNA so can’t infect).
What are the four ways that HepB is transmitted?
Four ways to transmit the virus:
1. BLOOD PRODUCTS
- Sexual transmission (high in MSM community)
- Horizontal transmission: person to person by sharing needles or blood transfusion or sex
- Vertical transmission: Mom is positive for chronic HepB and passes it off to the newborn
In which body fluids are there high amounts of Hep B? Where are there moderate or low/not detectable amounts?
High: blood (MOSTLY), serum, wound exudates
Moderate: semen, vaginal fluid, saliva
Low/not detectable: urine, feces, sweat, tears, breastmilk (so mothers can still breastfeed)
What is the geographic distribution of chronic HepB infection?
More in Canada, northern south america, africa, and china.
US doesn’t have as much bc of GREAT prenatal care so we don’t have a lot of vertical transmission. Instead it’s usually from drugs or multiple sexual partners
How does the outcome of HepB viral infection differ by the age at infection?
Newborn with hepB-90% chance they will not clear the infection (will develop chronic), BUT they are likely to not
have symptoms
Adults have good immune symptoms so will likely not develop chronic HepB, but adults are more likely to have
symptoms when they have acute HepB
What are the extra-hepatic manifestations of HepB?
If the person is viremic, it gets into different bodily fluids and that serves as a reservoir for transmission.
Can get into joints.
What does it mean if you have the core antibody of HepB in your serum? How do you differentiate?
Core antibody means you currently have hepatitis B or you had it in the past, and to distinguish between the two you look for IgM.
If IgM is present you currently have a Hepatitis B infection.
Describe the serology of someone with chronic HepB? What is their surface antigen, surface antibody, core IgM, and core IgG?
HepB surface antigen +
HepB surface antibody -
HepB core IgM -
HepB core IgG +
Describe the serology of someone who has recovered from HepB? What is their surface antigen, surface antibody, core IgM, and core IgG?
HepB surface antigen -
HepB surface antibody +
Hep B core IgM -
HepB core IgG +
Describe the serology of someone who has been vaccinated against HepB? What is their surface antigen, surface antibody, core IgM, and core IgG?
HepB surface antigen -
HepB surface antibody +
HepB core IgM NEGATIVE
HepB core IgG -
How do you differentiate between someone who had had the vaccine for HepB and someone who has recovered from a natural hepatitis B infection?
You don’t get the core unless you have or have had the infection. So if they have core IgG then they had the natural infection.
If they have no core IgG and no IgM but DO have the surface antibody, then they have been vaccinated.
In those that recover from Hep B, between week 24 where you’ve lost the surface antigen and week 32 when you have antibody, how do you diagnose acute HepB?
Core IgM, because although it’s being rapidly degraded there is still some present.
Describe the routine immunization for HepB? What is at increased risk for HepB?
Routine: all infacts and previously unvaccinated children by age 11.
Increased risk: multiple sex partners, partners or household contacts of a HBsAg-positive person, MSM, IVDU, travelers to endemic regions, or those with an occupational risk (exposed to blood or body fluids).
What should be done if there’s a HepB exposure in unvaccinated pts?
- Give HepB immune globulin (HBIG) preferably within 24 hrs but can be given up to 1 wk after. Second HBIG dose 1 mo after first.
- Hep B vaccine, preferabbly within 24 hr but can be given up to a week.
- 2nd dose 1 mo later
- third dose 6 mo after first
What should be given to HepB surface antigen positive mothers?
Give newborn both HBIG and vaccine.
What are characteristics of HepD?
Think HepDefective bc it cannot live by itself.
It lives on HepB. You have to have HepB in order to
get hepD. You can’t get hepD alone
ssRNA virus.
What is the difference between HBV-HDV coinfection vs superinfection?
Coinfection: acute HBV and HDV together, usually leads to eradication of both agents.
HDV superinfection occurs when someone already has chronic HBV: the majority of patients with HDV superinfection evolve to chronic HDV infection and hepatitis
What are characteristics of the HepC virus?
RNA virus
Produces 10^12 virions/day
What is the worldwide prevalence of HepC? What about in the US?
170-200 million worldwide
3-4 M in the US
What HepC genotypes exist in the US? Which is the most common? Why are these important to know?
1A: 37% - most common
1B: 30%
2: 10%
3: 6%
Genotype used to determine medication.
What are the most common sources of HepC infection?
IVDU (60%) and Sexual (15%)
What is the serology of someone with acute HepC infection with recovery?
ALT rises within the first 3 months and then falls. Symptoms occur at the peak of ALT (liver enzymes) around 3 months.
HCV RNA is present for about 6 months and then goes away.
Anti-HVC begins to rise after 2-3 months and increases for years.
What is the serologic pattern of acute HCV infection with progression to chronic infection?
Similar acute infection serology, but after ALT falls initially, it continues to rise and fall for years.
HCV RNA persists with a chronic infection.
Anti-HCV rises after 2-3 months, just like in the case of recovery.
How do you diagnose HepC?
HepC antibody seen in all exposures and remains present in all pts including those who spontaneously clear the virus or have successful treatment.
HepC viral RNA is present ONLY in those who are viremic.
What is the #1 cause of liver transplant death? What is it accelerated by?
HepC infection.
Death accelerated by alcohol use.
Why is the number of acute HepC infections currently on the rise?
Because of the opioid epidemic.
What is an example of a drug combination used to treat HepC?
Ledispavir combined with sofosbuvir.
Hepatitis ____ and ___ are responsible for causing acute hepatitis. What is the transmission and what’s most important for stopping it?
A and E
Fecal-oral transmission; virus shed before symptoms, increasing rapid spread.
HYGIENE most important for stopping transmission.
Inactivated vaccine for Hep ___ is effective.
Hep ___ is associated with higher mortality in pregnant women.
HepA inactivated vaccine is effective.
HepE associated with higher mortality in pregnant women.
Hep ___ and ___ are responsible for causing acute and chronic hepatitis. How are they transmitted?
B and C
Transmission: blood products, shared needles, sexual transmission (B»>C)
Hep ___ vaccine is safe and effective, and the goal is to vaccinate all infants in the US because elimination of Hep___ will eliminate Hep___ infection.
HepB.
Elimination of HepB will eliminate HepD infection.
Hep___ exists in genotypes and highly effective therapies now exist.
HepC
