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175 Cards in this Set

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HEPATITIS - CIBULL - WEDNESDAY FEB 7
define: hepatitis
a generic term for hepatocellular necrosis with variable degrees of inflammation +/- other features such as cholestasis, etc.
VIRAL HEPATITIS
during what phase are the morphologic changes of all types of viral hepatitis similar?
during the acute phase
what are the morphologic changes like in the acute phase (what areas are involved, and what areas are accentuated)?
patchy involvement of the entire lobule, with slight accentuation around the region around the central vein
what type of degeneration occurs in acute hepatitis?
ballooning degeneration
what are hepatocytes like, and what particular change has happened to some?
necrotic hepatocytes, some which have become mummified (acidophil bodies)
what cells are prominent in acute hepatitis?
Kupffer cells
does regeneration generally occur in acute hepatitis?
yes
what else occurs (list)?
inflammation, variable cholestasis, variable fatty change, etc.
what are the systemic clinical symptoms of acute hepatitis (5)?
1) malaise; 2) anorexia; 3) nausea; 4) fever (usually low grade); 5) immunologic findings (rash, arthritis, others)
what is urine like in acute hepatitis?
dark
what are other liver-relates symptoms of acute hepatitis (3)?
1) RUQ pain/tenderness; 2) jaundice; 3) itching
which hepatitis virus is a DNA virus?
HBV
what is the epidemiology of hepatitis A, B, and C?
A: fecal oral; B and C: parenteral
what is the incubation period for hepatitis A, B, and C?
2-6 weeks, 7-12 weeks, and 2-20 weeks
which can be spread through the blood?
B and C
which can be spread through feces?
A, possibly C
which can be spread by saliva?
A, B, and C
which can be spread perinatally?
B and C
how common is heterosexual sexual spread of hepatitis A, B, and C?
unknown, common, and uncommon
how common is homosexual sexual spread of hepatitis A, B, and C?
common, common, uncommon
how common is intra-family spread of hepatitis A, B, and C?
common, uncommon, uncommon
what is the icteric to anti icteric ratio of hepatitis A, B, and C?
1 to 1, 1 to 2, 1 to 4
all types may have a mild acute episode, but which type may have a severe acute episode as well?
HBV
which form has an abrupt onset?
HAV
what is the frequency of serum sickness-like-illness in hepatitis A, B, and C?
uncommon, common, rare
what is the mortality of hepatitis A, B, and C?
<0.5%, 1-3%, 1-2%
what is the rate of chronicity in hepatitis A, B, and C?
none, 5-10%, 50% or more
which increase the chance of liver cancer?
B and C
which has frequent transaminase fluctuation?
HCV
what is the antibody prevalence % in A, B, and C?
35-45%, 5-15%, 1-2%
what % of sporadic hepatitis cases are due to A, B, and C?
20%, 60%, 20%
what % of fulminant hepatitis cases are due to A, B, and C?
5%, 60%, 35%
what % of posttransfusion hepatitis cases are due to A, B, and C?
0%, 60%, 40%
what % of hepatitis cases in medical personnel cases are due to A, B, and C?
rare, 80%, 20%
what % of hepatitis cases in drug addicts are due to A, B, and C?
20%, 60%, 20%
what % of hepatitis cases in gay men are due to A, B, and C?
35%, 60%, 5%
what % of hepatitis cases in travelers are due to A, B, and C?
80%, 15%, 5%
of hepatitis B and C, which is most easily transmitted parenterally and by sexual contact?
hepatitis B is more easily transmitted both by sexual contact and parenterally
what % of HBV and what % of HCV cases have no risk factors?
30%, 40%
after personal contact, what is the most common source of HAV infection in the USA?
day care centers
what % of hepatitis A, B, and C virus recover completely?
99%, 85%, 15%
what % of patients with hepatis A, B, and C undergo massive hepatic necrosis?
<1%, 1%, 1-3%
of those who have massive hepatic necrosis with hepatitis A, B, and C, what % of each die?
50%, 67%, 87%
what is massive hepatic necrosis characterized by, histologicallly?
marked and uniform loss of hepatocytes with stromal collapse and loss of whole lobules
what happens later, if patient lives (2)?
1) fibrosis; 2) ductal proliferation
is this a type of cirrhosis?
no
what is the most common cause of liver failure?
acetaminophen (then other drugs, then hepatitis and other diseases)
HEPATITIS A VIRUS
what family is the hepatitis A virus?
picornavirus
what is the average incubation period for HAV, and what is the range?
average 30 days, range 15-50 days
what age group is most likely to get jaundice with HAV, and what % get it?
>14 yrs (70-80%)
what % of 6-14 year olds, and <6 yrs, get jaundice with HAV?
6-14 yrs: 40-50%
what are complications of HAV (3)?
1) fulminant hepatitis; 2) cholestatic hepatitis; 3) relapsing hepatitis
what are the chronic sequelae of HAV?
none
what age group has the highest mortality for HAV?
the elderly, by far: those over 49 have 17.5 per 1000 die, while those ages 30-49 have only 3.8 - those under 5 have slightly higher (3/1000) than those who are 5-29 (1.6/1000)
where is the highest concentration of infections HAV, and what is the concentration?
feces: 10^9 (infectious doses/ml)
what is the concentration in the serum and saliva?
serum is nearly 10^5, saliva just under 10^3 (infectious doses/ml)
HEPATITIS B VIRUS
what is the average incubation period, and incubation period range, of HBV?
average 60-90 days, range 45-180 days
what % get clinical illness (jaundice) with HBV, in those <5yr, and those >5yr?
<5yr, <10%; >5yr, 30-50%
what is the acute case fatality rate in hepatitis B?
0.5-1%
what % of those get chronic infection, in those <5yrs, and those >5yr?
<5yr, 30-90%, >5yr, 2-10%
what % have premature mortality from chronic liver disease?
15-25%
what are the three biggest risk factors, in order, for hepatits B?
1) heterosexual sex; 2) injecting drug use; 3) homosexual activity
what in the serology determines whether a person will recover from hepatisis B or progress to chronic hepatitis B infection?
whether or not they develop the anti-HBs antibody
of HBsAg, anti-HBs, and anti-HBc, which are positive during the early (presymptomatic) acute type B hepatitis?
only HBsAg
of HBsAg, anti-HBs, and anti-HBc, which are positive during the "window" of HBV infection?
anti-HBc (IgM)
of HBsAg, anti-HBs, and anti-HBc, which are positive during acute or chronic type B hepatitis?
HBsAg, anti-HBc
of HBsAg, anti-HBs, and anti-HBc, which are positive during recovery from type B hepatitis?
anti-HBs, anti-HBc
of HBsAg, anti-HBs, and anti-HBc, which are positive during immediate recovery phase from type B hepatitis or "low level" carrier state?
anti-HBc
of HBsAg, anti-HBs, and anti-HBc, which are positive after immunization with HBsAg?
anti-HBs
which can be positive long after hepatitis B infection?
either anti-HBs or anti-HBc
in what bodily fluids is HBV in high concentration (3)?
blood, serum, wounds
in what bodily fluids is HBV in moderate concentrations (3)?
semen, vaginal fluid, saliva
in what bodily fluids is HBV in low levels or not detectable (5)?
urine, feces, sweat, tears, breast milk
what is the msot severe consequence of hepatitis B infections due to?
the presence of the delta agent - a very small, defective RNA virus that requires HBV to cause disease
what does it increase the likelihood of (2) and how does it increase the likelihood of each?
1) fulminant hepatitis (with coinfection); 2) chronic active hepatitis (with superinfection)
***review hepatitis B graphs and charts (outcome by age, serological course)***
CHRONIC HEPATITIS
how long does chronic hepatitis last, and what viruses cause it?
>6 months, HBV and HCV
what seems to be happening with the terms used to describe chronic hepatitis?
they are being replaced by statements concerning etiology, severity (with regard to necrosis and inflammation), and stage with regard to the degree of fibrosis and progression toward cirrhosis
what are the current two classes of chronic hepatitis?
1) non-progressive (persistent); 2) progressive (active)
what % of what viruses account for chronic non-progressive (persistent) hepatitis?
10-12% of HBV, and a proportion of HCV as well
what is non-progressive (persistent) hepatitis like clinically?
prolonged, slow recovery without sequelae
what lab value changes, and what symptoms does this cause?
asymptomatic rise in serum transaminase
what morphologic changes occur in chronic non-progressive (persistent) hepatitis (2)?
1) mild inflammation; 2) evidence of hepatocellular degeneration and regeneration
what appearance often occurs due to the hepatocellular regeneration in non-progressive hepatitis?
cobblestone appearance
in what % of hepatitis B and C cases is chronic progressive (active) hepatitis seen?
in over 25% of hepatitis C, 1-3% of hepatitis B
in what other condition is it the clinicopathologic finding?
in autoimmune (lupoid) hepatitis
what is disease like?
multiple episodes of mild, often anicteric disease, with increased transaminase
how can it progress?
may be symptomatic initially, but may lead to cirrhosis, liver failure, and death
what is the morphologic pattern of chronic progressive (active) hepatitis?
bridging necrosis with "piecemeal" necrosis and inflammation
what is inflamed?
the limiting plate
what may or may not be present?
fibrosis, which may lead to progressive fibrosis and cirrhosis
what things are graded when assessing chronic hepatitis severity (3)?
1) grade of portal inflammatory activity; 2) grade of lobular inflammatory activity; 3) stage of fibrosis
what is the scale of portal inflammatory activity?
0 (none) to 4 (severe piecemeal necrosis)
what is the scale of lobular inflammatory activity?
0 (none) to 4 ( bridging necrosis)
what is the scale of fibrosis?
0 (none) to 4 (cirrhosis)
HEPATITIS C
how many genotypes and subtypes are there?
6 genotypes, >90 subtypes
what virus family does HCV belong to?
flaviviridae
what types of HCV account for 75% of cases in the USA?
1a and 1b
how does pathogenicity vary between HCV types?
all types are equally pathogenic
what do types 2 and 3 respond better to than type 1?
alpha interferon
what is the average incubation period, and incubation period range, for HCV infection?
average 6-7 weeks, range 2-26 weeks
what is the acute illness like, and what is the rate?
mild <20%
what % have chronic hepatitis?
70% (most asymptomatic)
what % go on to cirrhosis?
10-20%
what % die from CLD?
1-5%
what is the serological course like?
anti HCV always develops
what are ALT levels like?
increase in the symptomatic phase (2nd-5th months or so) and decrease in the first six months, then rise and fall in a jagged line pattern
what % of chronic liver disease is HCV related?
40-60%
how many people have chronic HCV infection in the USA?
2.7 million
hwo many people die from chronic HCV disease every year?
8,000 - 10,000
what is the most common source for HCV infection?
injecting drug use
what group has the highest prevalence of HCV?
hemopheliacs - although transfusions are no longer very dangerous
what % of IV drug users are infected after 5 years?
60-90%
what % of acute cases are transmitted sexually?
10-20%
what % of long term partners spread HCV?
1.50%
what type of transmission is most efficient?
male to female
what is the risk of transmission from a needle stick?
1.8% per stick (1/10 HBV)
what is the rate of perinatal transmission from women HCV-RNA positive at delivery?
5%
when is this rate higher?
when woman is HIV positive (17%)
what is the prognosis for infected infants?
they do well
what was it said there is no association with, in perinatal transmission (2)?
1) breast feeding; 2) delivery method
how common is severe hepatitis, in perinatal transmission?
rare
how common is household transmission of HCV?
rare, but not absent
how could it occur?
through percutaneous/mucosal exposures to blood (razors, toothbrushes, injections, folk remidies)
of those who have persistent hepatitis C, how many have stable chronic hepatitis (%)?
30%
of the other 70% which have variable (40%) and severe (30%) progression, how many respond to antiviral treatments?
35% respond, treatment fails in 65%
what are factors promoting progression of HCV (4)?
1) increased alcohol intake; 2) male; 3) over 40 years at time of infection; 4) coinfections (HIV, HBV)
HEPATITIS E VIRUS
what is the incubation period of hepatitis E (average and range)?
average 40 days, range 15-60 days
what is the overall fatality rate?
1%-3%
what group has a higher fatality rate, and what is it?
pregnant women - 15-25%
what other factor increases illness severity?
age
what are chronic sequelae?
none
what are most outbreaks associated with?
fecally contaminated drinking water
how do most US cases arise?
history of travel to HEV endemic areas
what type of transmission is minimal?
person to person
OTHER CAUSES OF HEPATITIS
what are other viral causes of hepatitis (4)?
1) HSV; 2) CMV; 3) adenovirus; 4) EBV
what alleles is autoimmune hepatitis associated with (4)?
HLA alleles - B8, Dr3, Dr52, and Dr4
what is the therapy (2)?
prednisone +/- azathioprine (not interferon as opposed to viral hepatitis, may require transplantation)
what is the clinical presentation like?
quite variable
who does type 1 (classic) autoimmune hepatitis typically occur in?
postmenopausal women
what may it present as (2)?
1) infertility; 2) endocrine dysfunction
what other diseases may it be associated with?
other autoimmune diseases such as thyroiditis, diabetes, or hemolytic anemia
what % recover without therapy?
only 20%
what antibodies are notably present (2)?
hypergammaglobulinemia with a wide variety, but most notably: 1) anti-smooth muscle; 2) ANA
who does type 2 autoimmune hepatitis often occur in?
female children (younger than type 1)
how does it compare to type 1?
often more aggressive and resistant to therapy than type 1
what antibody is it associated with?
anti-LKM-1 (liver kidney microsomal) rather than anti-smooth muscle
what does autoimmune hepatitis look like pathologically?
like viral chronic active hepatitis
what is one difference?
autoimmune hepatitis has more plasma cells in the portal infiltrate
what other diseases may look similar?
other autoimmune hepatic diseases such as primary biliary cirrhosis and sclerosing cholangitis
what are hints of drug induced liver disease (5)?
1) disproportionate necrosis; 2) eosinophilia; 3) fatty change; 4) granulomas; 5) disappropriate cholestasis
what are example drugs that cause liver damage (4)?
tylenol, INH, methyldopa, halothane, etc. (the list is long)