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96 Cards in this Set

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WHAT IS HEPATITIS DEFINITION
INFL OF LIVER
What is presentation of hepatitis
Jaundice, Fatigue, Nausea, Vomiting, Loss of Appetite, Joint Pain, Dark Urine, Light Stools, Abdominal Pain, Diarrhea, Fever (not always)
what are etiologies of hepatitis
Classic agents (Hep ABC...) as well as Yellow Fever, Cytomegalovirus, Epstein-Barr, Rubella, Mumps, ECHO viruses, others
What cells affected in hepatitis
Hepatocyte vs Kuppfer Cells
Physiology of Jaundice
Bile and Billirubin can't be metabolized so it comes out in skin/urine and stool as well.
Hepatitis in Cell Culture (diagnostics)
Hepatitis in Cell Culture (diagnostics)
cell culture - virus does not grow well
ANIMALS - look at liver histology after infection
SEROLOGY - ELISA,
markers for aby and agn are hard to grow
Hepatitis A Family/Genus
F Picornaviridae, G Hepatovirus
+RNA, 7.5 kb
Inc - 2-6 wks
low mortality(slightly higher in adults)
~15% prolonged or relapsing 6-9 months
Hepatitis A virus Epi
F/O - conc in shellfish
WW distribution - 1/3 Americans have evidence of past infection
vaccine greatly reduced cases in US
some epidemics up to 35K cases
persons at risk for hep a
-Household contacts of infected people -Sex contacts of infected people -Persons living in areas with increases rates (children) -Men who have sex with men -Drug users (IV and non-IV)
HAV control
Improve Sanitation Immunoglobulin-(pre or post exposure prophylaxis, short term) Vaccine
HAV vaccine
Licensed in 1995, No majors adverse effects Recommended for >2 year old who are travelers, men who have sex with men, drug users (IV or non-IV), clotting disorders (hemophilia), chronic liver disease, and children in high risk areas.
HEP E VIRUS -I
+RNA, 9.4 kb
FORMERLY CALICIVIRIDAE
first documented in Dehli in 1955
Domestic animals reservoir
F/O, probably WW
HEP E VIRUS - II
adolescence or early adult
inc 2-6 wks
acute hep w/o chronic carriage
mortality low X pregnant women
no TX or VACCINE
more prev in north africa and SW asia
HEPADNAVIRIDAE FAMILY
Hepatotrophic and DNA = hapadnavirus
Narrow host range determined by receptors
What are two genera of HEPADNAVIRIDAE
Orthohepadnavirus Genus - mammals
Avihepadnavirus -
Birds
Characteristics of Hep B virus
ds DNA
circular genome
enveloped - budding thru internal membranes - glycoproteins: HBV surface agn
Icosahedral Nucleocapsid - core protein HBV core agn
Does genotypic variation in Hep V have clinical importance
yes, maybe. Significant jgenotypic variation s exist
HBV PATHOGENESIS
Vigorous CTL - ACUTE HEP w/clearance
WEAK CTL - Asymptomatic Chronic Carrier
INTERMEDIATE CTL - Chronic carriage and chronic hep
is HBV a cytolytic infection of hepatocytes?
no
What is recruited for clearance of infection of Hep B
CTL response
HEP B EPI
WW DISTRIBUTION! - 350 mil chronic carriers
US - 1.2 mil CC
highest rates in 20-49 age (drugs sex vertical)
big decline since vaccine in 1980's
is there vertical and horizontal transmission in HBV
yes, both - vertical mom-child is what makes SE Asia levels very high
% of vertical transmission of HBV in SE Asia
up to 50% of babies - birth canal or through breast feeding
What kind of carriage does HBV vertical transmission result in
CHRONIC CARRIAGE
90% - neonates
30% - kids 1-5
6% after age 5
MOST ASYMPTOMATIC
WHAT IS DEATH RATE IN CHRONIC LIVER DISEASE PATIENTS
15-25% of chronically infected persons
Is Hepatitis B immunizing?
yes, only one infection
Predominant mode of transmission in industrialized world
sexual and parenteral (blood-borne)
Infection to disease ration in Hep B
10:1
What is a high blood titer in Chronic Hep B carriers
10 to the 10th/ml blood - blood is highly infectious
Is virus resistant to drying
pretty resistant, can last 1 week
How is Hep B transmitted thru sex
unprotected sex, especially if multiple partners
What are other blood-borne routes for Hep B
nosocomial exposure(hospital)
Household exposure(sharing razor, TB, etc with chronic carrier)
blood transfusion - 1/200000 units of blood
Hemodialysis
Tatoos and piercings
IVDU - IV drug use
What are possible results of Chronic HBV Infection
life-long asymptomatic carriage w/o obvious adverse effect
Spontaneous clearance(small fraction, usually when infected as adult)
Cirrhosis - hepatocytes replaced with necrotic tissue
Hepatocellular carcinoma - destruction of hepatocytes and regrowth selects for tumors
Integration into hepatocyte DNA with subsequent oncogenesis
What are antibodies to HBV infection and which are stronger
surface and core antigens
CORE - appears at onset of symptoms and persist for life. indicates previous or ongoing infection
SURFACE - previous infection or vaccination
When does HBV antigen show up
during acute and chronic hep. Indicates infection
What is the best correlate of infectivity in HBV
Hep B e Antigen. Secreted product of the nucleocapsid gene found during acute and chronic hep B
When is Hep B e antibody seen
temporarily during acute inf or during and after a burst in viral replication.
What does spontaneous conversion from e antigen to e antibody
predictor of long-term clearance of HBV in patients undergoing antiviral therapy and indicates lower levels of HBV.
What does IgM antibody to Hepatitis B core Antigen indicate
acute or recent infection(less than 6mos)
Describe multiple factors we need to assess for treatment
Clinical status
Hepatocellular enzyme levels
viral load
Liver function enzymes
Antibody and antigen status
biopsy
Is there good treatment for chronic HB
Treatments are experimental and still inadequate
what is a rate of the clearance in one trial
16 %
What are treatment for chronic HB
Pegylated alpha interferon(encapsulated)
Nucleoside or nucleotide analogues
Describe analogues(similar to the DNA, stops replication)
lamivudine
adefovir
entecavir
telbivdine
Resistant in chronic HBV is concern
yes(up to 10 % of cases in one study)
Describe prevention and control
Universal precautions in healthcare settings
Condoms
Testing of pregnant women
Hepatitis B immune globulin (HBIG)
HBV vaccine
What is HBV vaccine based on
S gene expressed in yeast
advantages and disadvantages of HBV vaccine
dis - 3 doses needed, can't clear in chronic carriers
adv - no major side effects,
Who/what is indicated for HBV vaccine
all children 1st 18 months
HCWs
IVDU
Hi risk sexual exposure
Living with chronic carrier
Immediately, post exposure
what are subviral agents
DEFECTIVE VIRUS
SATELLITE VIRUS
VIROID
VIRUSOID
PRION
What is a DEFECTIVE VIRUS
unable to replicate b/c of lack of complete genome. often competes with with complete virions for cell resources
what is SATELLITE VIRUS
depends on helper virus to provide some factor for replication
what is VIROID
Circular RNA molecule, contains no protein, too little NA to encode for replication.
what is VIRUSOID
ssRNA satellite virus
what is PRION
only protein!
Describe the Hepatitis D
Satellite HBV(cannot replicate in the absence of HBV)

Negative stranded RNA,

Covalently closed circular genome

1.7 kb

Genome encodes for a single polypeptide(hepatitis delta agent)
How % of people co-infected HBV and HDV
5-60 %
Describe the characteristics of transmission
Parenteral transimssion most efficient
Sexual transmission less efficient
Perinatal transmission rare
Describe coinfection in HDV
transmission w/ B virus and D virus simultaneously
Describe desease w/ coinfection B and D
Severe acute
Not chronic
Very aggressive desease
(Fulminant- 2-20%)
Describe the superinfection
~80 % develop chronic HDV infection
~80 % develop cirrhosis(compare w/ 15~30% w/ HBV alone)
Explain about serological characteristics of HBV-HDV coinfection
Symptoms and elevating ALT occur same time
anti-IgM rises w/ total anti- HDV

Total anti-HDV decreases slower than IgM

See the material
anti-HBs shows up after Ig M anti-HDV and total anti-HDV
Explain about serological characteristics of HBV-HDV superinfection
Jaundice occurs as a one of the symptoms.
HBsAg can see right after exposure

See the material
Symptoms are milder and total anti-HDV level stays high
Under superinfection HDV RNA is present throughout course(compared to coninfection which has short duration of RNA and HBs Ag)
Describe the prevention of HBV-HDV coinfection
pre- or post- exposure prophylaxis to prevent HBV infection
Describe the prevention of HBV-HDV superinfection
Education to reduce risk behaviors among persons w/ chronic HBV.
Describe the characteristics of Hepatitis C virus
Family Flaviviridae
Genus Hepacivirus
Positive-stranded RNA
Genome 9.4 kb
Six major genotypes or clades w/ no cross-protection
which symptoms are milder, super of coinfection
Super-chronic-cirrohsis
Describe the characteristics of WW distribution
~3 % of the world chronically infected
~2.7 million chronically infected in the U.S
19% population in Egypt(from schistosomiasis vaccine)
Is initial HCV infection mild and what are the long term problems
mild or asymptomatic
chronic carriage more than 50 %
Cirrhosis and Hepatocellular carcinoma
What are the risk factors for HCV
IVDU
Transfusion
Transplant
Needle stick/ iatrogenic
Birth to HCV-infected mother
Sex w/ infected partner
What are the % of biggest risk factor of HCV infection
60% IVDU
50% Sexual
Male>Female
Hemophilia has high level in blood transmission HCV
What behavioral change happened early 2000 to reduce the incidence of HCV
reduced IVDU- moved on to crack smoking
What is cause of non A non B hepatitis
HCV- Late 80's discovery
What is prevalence of HCV following IVDU
rapidly acquired 30% - 3 yrs
50% - 5 yrs
4 X more common that HIV
Highly efficient
Post-transfussion HCV
See the material
Describe occupational transmission of HCV
Inefficient
Hollow bore needles
10 times lower than for HBV infection
What kind of people has a possibility of perinatal transmission
Women HCV-RNA positive at delivery
Average rate of infection -6%
If women co-infected w/ HIV -17%
Severe hepatitis in infant is rare
No relation w/ breast feeding and delivery method
Describe characteristics of Sexual transmission of HCV
efficiency is low
(rare btwn long-term steady partners)
MSM no higher risk than heterosexuals
Male to female>Female to male transmission
What are risk factors of HCV sexual transmission
Infected partner
multiple partners
early sex
non-use of condoms
other STDs
sex w/ trauma
Through what kind of things is household transmission occur in HCV
Through percutaneous/ mucosal exposures to blood
(contained equipment used for home therapies; IV therapy, injections)
Theoretically through sharing of contaminated personal articles(razors, toothbrushes)
Household transmission-rare
What are other potential exposures to blood
No or insufficient data showing increase risk relate to,
Intranasal cocaine use
Tattooing
Body piercing
Acupuncture
What will happen after HCV Infection and describe % of each of these
Chronic infection- 60-85%
Chronic hepatitis- 10-70%(most asymptomatic)
Cirrhosis 5-20%
Mortality from chronic liver disease- 1-5 %
What are factors promoting HCV progression or severity
Increased alcohol intake
Male gender
Age>40 years at time of infection
HIV co-infection
Chronic HBV co-infection
What are characteristics of HCV clinical
Incubation period; 6-7 weeks(range2-26w)
Acute illness
less than 20% symptomatic
Case fatality rate low
Describe characteristics of serologic pattern of Acute HCV infection w/ recovery
ALT elevates around 1 month, and decreases around 6 months.
anti-HCV gets high
HCV RNA shows up from 1months after exposure and disappears less than 1 year.
Symptoms + or -
Describe characteristics of Acute HCV infection w/ progression to chronic Infection
Symptoms; +/-
Anti-HCV; high
increase from 1 month, from 6 months starts wax and waning for ALT and HCV RNA
How evaluate chronic HCV infection
Same process for HBV,
liver function enzymes
Assess severity and possible treatment depending on,
Clinical status
Viral load
Antibody and antigen status
Biopsy
varies from Dr to Dr.
Describe characteristics of management of chronic HCV infection
Treatments; experimental and inadequate
Clearance of infection; <50 %
Involve combinations of ; Pegylated alpha interferon
Nucleoside or nucleotide analogues(ribavirin)
Describe the name of nucleoside analogues
Lamivudine, adefovir, entecavir, telbivudine
(all drugs block some form of replication)
What is a biggest concern in management of chronic HCV infection
Emergence of resistant viruses
Describe ways for prevention and control of HCV
Screen and blood donors
Virus inactivation of plasma-derived products
Safe injection and infections control practices
Describe the risk-reduction counseling and services
Obtain history of high-risk drug and sex behaviors

Provide information on minimizing risky behavior, including referral to other services

Vaccinate against hepatitis A and/or hepatitis B
Who should take HCV test
<Risk of infection>
Ever injected illegal drugs
Received clotting factors made before 1987
Received blood.organs before July 1992
Ever on chronic hemodialysis
Evidence of liver disease
<Risk of exposure>
Healthcare, emergency, public safety workers after needle stick/ mucosal exposures to HCV-positive blood
Children born to HCV-positive women
What are ways for reducing harm to liver
Limit or abstain from alcohol
Vaccinate against hepatitis A and B
Refer to support group
What routes of transmission of HCV to others should be used to prevent
Direct exposure to blood
Perinatal exposure
Sexual exposure
What viruses have first and second highest risk of needle stick infection
1 HBV(HBs Ag+, HBeAg+);20-30% clinical hepatitis, 37-62% Seroconversion
2 HBV(HBsAg+, HBeAg-); 1-6% clinical hepatitis, 23-37% Seroconversion
(eAg=more infectious sAg=less infective)

HCV 0-7%, HIV-1 0.3%