EXAM 3 Hepatitis Flashcards
describe acute hepatitis
- incubation = several weeks
- flu-like symptoms, fever, myalgias, pharyngitis
- jaundice, enlarged and painful liver
- marked elevations in LFTs (liver function tests)
- resolves spontaneously
hepatitis ___ can cause acute hepatitis
A, E, and B (B causes both)
hepatitis ___ causes chronic hepatitis
C and B (causes both)
describe chronic hepatitis
- often asymptomatic
- physical exam can show signs of portal hypertension or liver inflammation
- LFTs can be normal or elevated
- persists for years or decades
what type of virus is hepatatitis A?
non-enveloped ssRNA virus
the incidence of hep A among children in developing countries reaches ___%
100%, with subsequent life-long immunity (because the hep A results in acute hepatitis which will resolve itself, so the child will develop immunity)
what is the transmission of hep A?
fecal-oral route
what is the incubation period of hep A?
28 days (15-50 days)
describe outbreaks of hep A
foodborne outbreaks are common, and are related to overcrowding, poor sanitation, and polluted water sources
hep ___ is the most common cause of acute hepatitis
A
what are the risk factors for contracting hep A?
day care, international travel, MSM (men who have sex with men), IV drug use
shedding of hep A occurs ___ weeks prior to acute hepatitis and continues 1 week after onset of ___
- 1-3
- jaundice
with hep A, most adults will have ___, while ___% of children are ___
- symptoms
- 70%
- asymptomatic
describe the diagnosis of hep A
exposure + acute hepatitis + anti-HAV IgM
what are the complications with hep A?
- coagulopathy
- encephalopathy
- renal failure
- these complications are rare; hep A usually resolves itself
describe prevention of hep A
- two formalin-inactivated vaccines were FDA-licensed in mid-1990s
- two-dose vaccine with >94% pts demonstrating neutralizing antibodies one month after first dose
- two doses recommended: 0 and 6-12 months
- hep A immunoglobulin is available for immediate passive immunity (post exposure prophy if immune compromised)
describe hep A prevention via vaccination
- everyone should get vaccinated
- children most importantly
describe the virology of hep E
non-enveloped ssRNA virus
hep ___ causes acute hepatitis that is clinically indistinguishable from HAV
E
how is hep E spread?
fecal contamination of water
person-to-person spread is rare
what are the areas where hep E is endemic?
asia, north africa, middle east
the incubation of hep E is ___ days
40
which hepatitis virus can be acute or chronic?
B
describe the virology of hep B
- enveloped DNA virus: partially dsDNA / ssDNA
- 3200 nucleotides total: smallest known human DNA virus
the compact, overlapping reading frames of hep B produce what?
- surface protein (HBsAg)
- core nucleocaspid protein (HBcAg)
- HBeAg
- DNA pol (DNA- and RNA-dependent DNA polymerase with RNase H activity)
- HBxAg (transactivator, clinical relevance unknown, can bind p53)
there are 250 million ___ carriers worldwide
hep B chronic
hep B is responsible for ___ deaths annually worldwide
1 million
how many people in the US have chronic hep B?
2 million
transmission of hep B can occur in what 3 ways?
perinatal, parenteral, sexual
___ transmission of hep B predominates in high prevalence areas
perinatal
- infection rate of infants born to HBeAg+ mothers = 90% (decrease to 30% if HBeAg-)
- neonatal vaccination efficacy = 95%
describe parenteral transmission of hep B
- HBV is the most commonly transmitted blood-borne virus in healthcare settings (HBV > HCV > HIV)
- common among intravenous drug users
___ transmission of HBV is the most common mode of transmission in low-prevalence areas
sexual
___ is a clinical marker of active HBV infection
E antigen (HBeAg+)
30% of newly hep B infected adults will have ___ hepatitis
acute
perinatal/childhood primary infection is asymptomatic
the rate of progression of acute hep B to chronic hep B inversely correlates with ___.
perinatal transmission: ___% progress to chronic disease
infection between ages 1-5: ___%
adult-acquired infection: ___%
- age
- 90%
- 20-50%
- <5%
describe the relationship between chronic infection and age at infection, and symptomatic infection and age at infection
- chronic infection: more common in younger children, is reduced with age
- symptomatic infection: asymptomatic until about 12 months of age, then increases with age

chronic hep B has a broad spectrum of illness. describe
from asymptomatic to chronic hepatitis to cirrhosis / HCC (hepatocellular carcinoma - liver cancer)
what are factors that influence the natural history of chronic hep B infection
- virus replication
- host immune response
- gender (men more likely to have acute flares)
- alcohol consumption
- viral co-infection
what are the lab predictors of poor outcome of chronic hep B infection?
- HBeAg positivity
- HBV serum DNA level >2000 IU/ml
- high titer HBsAg
- necro-inflammation on liver biopsy
describe the extra-hepatic manifestations of chronic hep B?
- present in up to 20% of chronic HBV patients
- related to circulating immune complexes
- polyarteritis nodosa (autoimmune disease)
- membranous nephritis and MPGN (nephrotic range proteinuria)
- aplastic anemia
what is hepatocellular carcinoma?
- a possible result of chronic hep B infection
- associated with cirrhosis of any cause including HBV
- HCC can develop in chronic HBV in absence of cirrhosis
- HBV DNA level, HBeAg status, co-infection with HCV and HDV
- screen for HCC among chronic HBV patients (liver U/S q6 mo)
describe hep B diagnosis with HBV surface antigen and antibody
- HBsAg is serologic hallmark of infection (1-10 weeks)
- persistent HBsAg for >6 mo = chronic infection
- clearance of HBsAg followed by development of anti-HBs, conferring life-long immunity
- window period in between decrease in HBsAg and increase in anti-HBs can be several months
- co-existence of both HBsAg and anti-HBs: regard as chronic carrier state
describe diagnosis of hep B based on HBV core antigen and antibody
- HBcAg is intracellular and never detected in serum
- anti-HBc persists throughout infection
- IgM anti-HBc may be only positive test in window period of acute infection
- total/IgG anti-HBc is present in recovery (+anti-HBs) and in chronic disease (+HBsAg)
describe diagnosis of hep B via e antigen and antibody
- HbeAg is a marker of replication and infectivity
- correlates with high viral loads
- conversion from HBeAg to anti-HBe typically associated with disease remission
describe diagnosis of hep B via HBV serum DNA PCR
- used for initiation and monitoring of antiviral therapy
in the treatment of hep B, what are the two types of antivirals?
IFN and nucleoside analogs
in hep B, when should you treat?
when there is HBV DNA >20,000 (HBeAg+) or >2,000-20,000 (HBeAg-)
and
disease (increased ALT and/or necroinflammation on liver biopsy)
___ and ___ are the first line of defense in the treatment of hep B in the US
tenofovir and entecavir
for the prevention of hep B, ___ vaccine is safe and highly efficacious against all HBV serotypes, and is useful as ___ prophylaxis (+/- HBIg)
recombinant antigen, post-exposure
describe the virology of hep D
defective ssRNA virus
hep D is a passenger virus accompanying hep ___
B
___% of HBV+ patients are co-infected with HDV globally
10%
low in US and europe, common in IVDU
endemic in mediterranean and north africa
why would it be important to vaccinate against hep B to avoid contracting hep D?
because without hep B, you cannot get hep D
can hep D be cleared by the host?
yes, that is typical
describe HDV super-infection in chronic HBV+ pts
- leads to chronic HDV infection (>90%)
- suppresses HBV replication
- fulminant hepatitis, cirrhosis and HCC much more common
how is hep D diagnosed?
PCR or anti-HDAg IgM/IgG
___ is the only approved treatment for the management of hep D (low success rate)
IFN-alpha
describe the virology of hep C
enveloped RNA virus in flavivirus family
related to yellow fever, dengue, and west nile
describe the transmission of hep C
- blood borne transmission
- blood transfusion, IVDU, needle sticks, sex
hep C leads to chronic hepatitis in ___% of cases
60-80%
what are the long term risks associated with hep C
cirrhosis and hepatocellular carcinoma
what are the tests available for the diagnosis of hep C?
- antibody immunoassay
- molecular testing for presence of HCV RNA
in the diagnosis of hep C, always start with ___
HCV antibody
- negative HCV Ab = no infection present
- positive HCV Ab = past or present infection, need to check for virus
describe how hep C can also be diagnosed via HCV RNA
- positive = active infection
- negative = cleared infection (or false positive Ab)
who should be tested for hep C?
everyone born between 1945 and 1965
potential exposures
describe the management of hep C
- always test for HIV and hep B
- determine genotype (for drug selection)
- evaluate for liver damage and cirrhosis
what is the treatment goal for hep C management?
reduction of HCV RNA to undetectable levels
describe sustained virologic response in the management of hep C
- absence of viral RNA 12 weeks after treatment
- 97-100% chance of cure