viral hepatitis Flashcards

1
Q

hepatitis A

What virus causes?
What is the epidemiology of?
What is the incubation period?
Is viremia present?
Why is it rare in developing countries?
A

picornavirus in genus hepatovirus
epidemiology like that of polio
overt disease rare in low sanitary conditions because infection of infants results in passive–> active immunity without disease
30 day incubation period
fecal excretion of virus takes several weeks, viremia takes about a week
viremia infects liver
rare in developing countries because the virus is prevalent in these countries and there is passive immunity from mother coupled with secondary active immunity from exposure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

hepatitis A - pathogenesis

When does viremia occur?
What are symptoms?

A

after about 1 week, viremia results in infection in liver
viral growth in liver cells results in anorexia, nausea, fever, and jaundice because of deposition of bilirubin in skin
abnormal liver function tests (LFTs)
damage in liver due to lysis of infected cells to release progeny virions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

common causes of focal epidemics (5) for Hepatitis A

common causes as in social situations that benefit virus communication

A

1: outdoor summer events with inadequate sanitary facilities
2: from raw or inadequately cooked shellfish contaminated by sewage
3: within one family (spread by children’s fecal contamination)
4: from infected food handler in USA
5: from fecally contaminated food, usually imported

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

pooled gamma globulin for Hep A

How long is this effective?
How effective is it?

A

used to use intermuscluarly injected pooled human gamma globulin to protect travelers to areas when hep A is epidemic
vaccine now available so this is used primarily after suspected exposure
passive immunity does the following:
1: prevents jaundice and malaise after infection
2: doesn’t completely prevent liver damage - elevated liver tests still occur
3: provides protection for about 4 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

heme excretion

(pathway and jaundice)

A

1: old RBC (heme) converted to bilirubin in spleen
2: transported as bilirubin-albumin complex in the blood
3: converted to bilirubin-glucuronide in liver
4: excreted in bile as the above complex
5: excreted in feces as bilirubin metabolites - feces brown because of bilirubin
with viral hepatitis, step 3 is blocked so there’s a buildup of bilirubin-albumin => jaundice = yellowed skin, dark urine because excreted through urine, pale feces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Hep A vaccine

Is it killed or live?
Who is recommended to receive the vaccine?

A

formaldehyde-killed
recommended for all children, travelers to highly epidemic areas, men who have sex with men, persons who regularly receive blood products, adults in states with history of elevated rates of infection, and people with chronic liver disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

testing for Hep A

Explain how to test for Hep A. What are do positive and negative results mean from (two specific Ig-type tests)

A

can be cultured in lab but procedure not generally available
use serological test for antibody to virus
look for anti-HAV-IgG and anti-HAV-IgM
if negative for both antibodies, disease not Hep A
if negative for IgM but positive for IgG, has had hepA in the past or has had the vaccine but that’s not the current ailment
if positive for both antibodies, has acute infection or recent vaccination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how to study epidemiology of acute infection

A

1: ensure that it’s epidemic and not just better detection of disease
2: plot cases on map, looking for clustering that could suggest pattern of transmission
3: compare types of people infected to look for mode of exposure (occupation, age, food consumption, etc.)
4: plot timeline of appearance of new cases, looking for incidence and prevalence - in simple epidemics all individuals clustered around the incubation period

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

prevalance

What does this term mean?
How does it compare with “incidence”?

A

total number of cases (expressed per 100/1000/10000 individuals)
so if we were to come up with a vaccine for AIDS tomorrow, the prevalence of AIDS wouldn’t change, because the same number of people will still be infected, but the incidence will

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

common-source epidemic

What does this term mean?

A

simplest type of epidemic
all individuals are infected at roughly the same time and new cases are clustered around the incubation period (so get very pointy bell curve when you plot incidence and time)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

hepatitis B virus

What type of virus is this?
What type of nucleotide does it have?
What special replication machinery does it have?

A

hepadnavirus
virion has circular DNA that is mostly double stranded but has some single-stranded regions
contains enzyme for replication of its genome - often called DNA polymerase but is actually a reverse transcriptase
has lipoprotein envelope with viral glycoproteins as outer layer
unique because translates from RNA to DNA - has reverse transcriptase (Pol protein)
sloppy replication - get over production of virions but that don’t have viral genome so not infectious - not clear why this happens, but might be to confuse immune system by having too many targets - useful as diagnostic test - virus can suppress antibody response against it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

hep B disease

What is the incubation period?
What happens to the liver of acute and chronic carriers?

A

incubation period about 70 days
hepatocytes damaged by immune system
chronic carriers have chronic hepatitis and primary liver carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

transmission of Hep B

What are modes of transmission of?

A

1: blood transfer with infected blood
2: sexual transmission
3: perinatal infection of neonates by their mothers
4: sharing needles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

tests for Hep B

What are the tests?

A

serological tests for virus and antibody

hep B antigens (HB-Ags) will be present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Hep B antigens (HB-Ags)

What percentage of patients have Ags for life?

A

complex mixture of virions and subviral particles
divided into two groups depending on location in virions - core (nucleocaspid) or surface (envelope glycoproteins)
Ag usually only seen in serum for several weeks after infection, but about 5% of patients get chronic infection so Ag persists for years or for life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

HBeAg

Is this a core or envelope antigen?
Is it indicative of any particular illness?
Are Abs present? In which patients?

A

Hep B antigen - circulating core antigen e
strongly correlated with presence of infectious HBV and with progression to carcinoma in chronically infected patients
antibodies to HBeAg (and HBsAg) are usually suppressed in chronically infected patients but high in patients who have cleared the virus

17
Q

hepatocyte damage in Hep B

What is the mechanism?

A
immunologically mediated
cytotoxic T cells recognize HBV peptides presented on MHC class I on the cell surface
18
Q

perinatal transmission of hepatitis B

What percentage of infected infants will be chronic HBV carriers?
What percentage will die of liver cancer?
What is preventive treatment?

A

from HB-Ag positive mothers to neonate
90% will become chronic HBV carriers
25% will die of liver carcinoma or chronic hepatitis
can reduce incidence of infection with passive immunization with HB-immune globulin and with active immunization after birth
routine screenings of all pregnant women

19
Q

post-transfusion hepatitis

What is the only problem that persists with obtaining Hep B blood?

A

no longer a problem because the following not allowed to donate blood:
1: former hepatitis patients
2: people who have lived with a hepatitis patient in the last 6 months
3: people who have had a transfusion in the past 6 months
4: people whose serum test positive for HB-Ag
window period longer when serological test used than with PCR-based test
PCR detection prevents most transmission of HBV and HVC but post transfusion transmission of other hepatitis viruses still a problem

20
Q

killed vaccines (review)

A

purified virions are disrupted and the antigens that elicit neutralizing antibodies are purified
chemical inactivation used to eliminate residual live virus
can also clone viral genes that encode neutralizing antibodies and express them in yeast or other microbe
both types of subunit vaccines

21
Q

subunit vaccines

A

contain only antigenically important subunits of virions

killed vaccines because no infections virions are present

22
Q

passive immunization for Hep B

What populations are necessary for pooled IgG?
When is it effective?

A

pooled human IgG from serum of persons with large amounts of Ab against HBV can protect against overt HBV
used for passive immunization of neonates if needed
pooled normal human gamma globulin usually not adequate (unlike with hep A - for hep B, concentration of antibody in pooled human serum not usually high enough)
also effective post exposure to prevent infection and for infected infants

23
Q

subunit vaccine for Hep B

Recommended for who?

A

HB-Ag can be produced in recombinant form
consists of individual viral proteins expressed by yeast or bacteria then purified and formulated with an adjuvant
killed vaccine
recommended for high-risk groups, hospital personnel
because hep B is an STD, infections take place after puberty, so immunization in early childhood is important

24
Q

hepatitis C virus

What type of Virus is Hep C?
Enveloped?
Nucleotide status?
Diagnostic status?
Incubation period?
What percentage of infected people have chronic infection?
A

a flavivirus
enveloped plus-stranded RNA
causes most nonA-nonB hepatits
can be detected by PCR test for the RNA (and by serological, but that’s less sensitive)
transmitted by blood transfusion, needle-sharing, STD
60 day incubation period
results in immunologically mediated damage to hepatocytes
worse than hep B because in hep B on 5% of patients get chronic disease, whereas with hep C 25% get chronic disease

25
Q

window period

A

interval between the time that a donor can transmit a given virus and the time that that donor’s infection can be detected by a given test done with donated blood
problem in transplants and transfusions

26
Q

steps to make hep C antigen

What are the?
Do you use convalescent serum or acute serum?

A

1: take blood from a donor caused by nonA-nonB hepatits in a recipient who recovered
2: infect a chimpanzee with the donor’s blood
3: ultracentrifuge the chimp’s serum to get a pellet of “virus”
4: randomly clone the DNA adn RNA molecules in the pellet, hoping to clone the viral genome
5: express the cloned DNA in E. coli
6: choose the clone that reacts with convalescent serum but not with acute serum (serum collected before and after infection from recipient of antibody)

27
Q

timecourse of hep C infection

A

1-2 weeks after exposure: HCV RNA detectable
2-6 weeks: elevated ALT
4-8 weeks: HCV antibody detectable
24 weeks: HCV clearance or persistence
about 25% have persistence => chronic disease
15-30 years (in chronic cases) get cirrhosis

28
Q

similarities between Hep B and C

A

long incubation periods
cause both acute and chronic disease but more common in HCV
prodromal symptoms of rash and arthritis in acute
substantial risk for primary hepatocellular carcinoma
transmitted as STD and by needle-sharing (so look for needle tracks)
transmitted perinatally (HBV > HCV)

29
Q

prodromal symptoms

What does this term mean?

A

nonspecific symptoms that appear before the definitive symptom (jaundice, in the case of hep A and B)

30
Q

treatment of chronic viral hepatitis

A

1: prolonged treatment with alpha-interferon - expensive, has adverse side effects, and low rate of success
2: lamivudine - chain terminating reverse transcriptase inhibitor originally used to treat AIDS
3: responds better to interferon plus ribavirin
4: telaprevir and boceprivir recently approved for hep C - inhibit essential protease - use combined with alpha interferon plus ribavirin - can eliminate persistent infection in many patients

31
Q

hep B tumorogenesis

What are the rates of cancer from Hep B?
What cause cancer?
Does the virus integrate with genome?

A

due to hep B, leading cause of cancer deaths worldwide (500000 annually)
5% of infected become chronic carriers - 2-4% of these get carcinoma
tumors have integrated hep B virus DNA - suspected that in some cases integration near a cellular proto-oncogene leads to over expression and induces transformation - some viral proteins may act as oncogenes
also likely due to constant destruction of liver cells - must be regenerated, which can result in mutations in the process

32
Q

hep C tumorogenesis

What causes?
Does the virus integrate with genome?

A

virus contains no known oncogenes
chronic immune response likely promotes tumor development
alcoholism speeds up liver damage and rate of carcinoma
virus does not integrate into genome

33
Q

hepatocellular carcinoma epidemiology

What is the prognosis for surgical resection of LV in hepatitis?

A

most common primary liver malignancy
worldwide incidence > 600000 cases per year
more common in men than in women
can have as high as 50% rate of recurrence following resection

34
Q

risk factors for hepatocellular carcinoma

A

1: cirrhosis or advanced fibrosis
2: males > females
3: older age
4: comorbidities with HBV, HIV, alcohol use
5: african american race
6: HCV patients with diabetes or insulin resistance
7: smoking (possibly)

35
Q

hepatitis D

What type of nucleotide?
How is it reliant on Hep B?
How is it diagnosed?

A

defective RNA virus (formerly called delta agent)
Circular negative RNA
can produce infectious progeny only in cells also infected by hep B so only those who have acute or chronic hep B can get it
needs hep B because D’s genome doesn’t encode for its own envelope proteins - needs B’s envelope
can get serological diagnosis because there is one protein unique to hep D - PCR diagnosis still better

36
Q

hepatitis E virus

What is enveloped status?
What is nucleotide status?
What is transmission?
What countries is this disease found in?

A

non-enveloped plus-stranded RNA virus
transmitted by fecal-oral pathway
seems to mostly occur from contaminated water or food, person-to-person transmission rare
almost exclusively in developing countries - mortality rate high in pregnant women

37
Q

similarities between different hep types (A through E)

A and E
B, C, and D
B and C
A, C, E

A

A and E are fecal-oral transmission, only cause acute disease in patients with normal immune response, shorter incubation period (30 days)

B, C, and D are transferred by blood and blood byproducts, venereally and perinatally - cause chronic disease with liver damamge - long incubation period (50-70 days)

B and C, if chronic, can cause hepatocellular carcinoma

A, C, E: +ssRNA

38
Q

incidence

A

number of new cases of a disease during an epidemic

so if we were to come up with a vaccine for AIDS tomorrow, the prevalence of AIDS wouldn’t change, but the incidence will become zero because there will be no new cases

39
Q
What are the nucleic acid structures of
Hep A
Hep B
Hep C
Hep D
Hep E
A
A: +ssRNA (non-enveloped)
B: dsDNA Circular with some ssDNA (enveloped)
C: +ssRNA (enveloped)
D: -ssRNA Circular (enveloped)
E: +ssRNA (non-enveloped)