Path 3 Hepatitis

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HEPATITIS - CIBULL - WEDNESDAY FEB 7

Front 3

define: hepatitis

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a generic term for hepatocellular necrosis with variable degrees of inflammation +/- other features such as cholestasis, etc.

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VIRAL HEPATITIS

Front 7

during what phase are the morphologic changes of all types of viral hepatitis similar?

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during the acute phase

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what are the morphologic changes like in the acute phase (what areas are involved, and what areas are accentuated)?

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patchy involvement of the entire lobule, with slight accentuation around the region around the central vein

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what type of degeneration occurs in acute hepatitis?

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ballooning degeneration

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what are hepatocytes like, and what particular change has happened to some?

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necrotic hepatocytes, some which have become mummified (acidophil bodies)

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what cells are prominent in acute hepatitis?

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Kupffer cells

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does regeneration generally occur in acute hepatitis?

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yes

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what else occurs (list)?

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inflammation, variable cholestasis, variable fatty change, etc.

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what are the systemic clinical symptoms of acute hepatitis (5)?

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1) malaise; 2) anorexia; 3) nausea; 4) fever (usually low grade); 5) immunologic findings (rash, arthritis, others)

Front 15

what is urine like in acute hepatitis?

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dark

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what are other liver-relates symptoms of acute hepatitis (3)?

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1) RUQ pain/tenderness; 2) jaundice; 3) itching

Front 17

which hepatitis virus is a DNA virus?

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HBV

Front 18

what is the epidemiology of hepatitis A, B, and C?

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A: fecal oral; B and C: parenteral

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what is the incubation period for hepatitis A, B, and C?

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2-6 weeks, 7-12 weeks, and 2-20 weeks

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which can be spread through the blood?

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B and C

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which can be spread through feces?

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A, possibly C

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which can be spread by saliva?

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A, B, and C

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which can be spread perinatally?

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B and C

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how common is heterosexual sexual spread of hepatitis A, B, and C?

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unknown, common, and uncommon

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how common is homosexual sexual spread of hepatitis A, B, and C?

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common, common, uncommon

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how common is intra-family spread of hepatitis A, B, and C?

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common, uncommon, uncommon

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what is the icteric to anti icteric ratio of hepatitis A, B, and C?

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1 to 1, 1 to 2, 1 to 4

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all types may have a mild acute episode, but which type may have a severe acute episode as well?

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HBV

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which form has an abrupt onset?

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HAV

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what is the frequency of serum sickness-like-illness in hepatitis A, B, and C?

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uncommon, common, rare

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what is the mortality of hepatitis A, B, and C?

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<0.5%, 1-3%, 1-2%

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what is the rate of chronicity in hepatitis A, B, and C?

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none, 5-10%, 50% or more

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which increase the chance of liver cancer?

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B and C

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which has frequent transaminase fluctuation?

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HCV

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what is the antibody prevalence % in A, B, and C?

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35-45%, 5-15%, 1-2%

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what % of sporadic hepatitis cases are due to A, B, and C?

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20%, 60%, 20%

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what % of fulminant hepatitis cases are due to A, B, and C?

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5%, 60%, 35%

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what % of posttransfusion hepatitis cases are due to A, B, and C?

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0%, 60%, 40%

Front 39

what % of hepatitis cases in medical personnel cases are due to A, B, and C?

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rare, 80%, 20%

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what % of hepatitis cases in drug addicts are due to A, B, and C?

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20%, 60%, 20%

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what % of hepatitis cases in gay men are due to A, B, and C?

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35%, 60%, 5%

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what % of hepatitis cases in travelers are due to A, B, and C?

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80%, 15%, 5%

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of hepatitis B and C, which is most easily transmitted parenterally and by sexual contact?

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hepatitis B is more easily transmitted both by sexual contact and parenterally

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what % of HBV and what % of HCV cases have no risk factors?

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30%, 40%

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after personal contact, what is the most common source of HAV infection in the USA?

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day care centers

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what % of hepatitis A, B, and C virus recover completely?

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99%, 85%, 15%

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what % of patients with hepatis A, B, and C undergo massive hepatic necrosis?

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<1%, 1%, 1-3%

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of those who have massive hepatic necrosis with hepatitis A, B, and C, what % of each die?

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50%, 67%, 87%

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what is massive hepatic necrosis characterized by, histologicallly?

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marked and uniform loss of hepatocytes with stromal collapse and loss of whole lobules

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what happens later, if patient lives (2)?

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1) fibrosis; 2) ductal proliferation

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is this a type of cirrhosis?

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no

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what is the most common cause of liver failure?

Back 52

acetaminophen (then other drugs, then hepatitis and other diseases)

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HEPATITIS A VIRUS

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what family is the hepatitis A virus?

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picornavirus

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what is the average incubation period for HAV, and what is the range?

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average 30 days, range 15-50 days

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what age group is most likely to get jaundice with HAV, and what % get it?

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>14 yrs (70-80%)

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what % of 6-14 year olds, and <6 yrs, get jaundice with HAV?

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6-14 yrs: 40-50%

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what are complications of HAV (3)?

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1) fulminant hepatitis; 2) cholestatic hepatitis; 3) relapsing hepatitis

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what are the chronic sequelae of HAV?

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none

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what age group has the highest mortality for HAV?

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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)

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where is the highest concentration of infections HAV, and what is the concentration?

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feces: 10^9 (infectious doses/ml)

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what is the concentration in the serum and saliva?

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serum is nearly 10^5, saliva just under 10^3 (infectious doses/ml)

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HEPATITIS B VIRUS

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what is the average incubation period, and incubation period range, of HBV?

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average 60-90 days, range 45-180 days

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what % get clinical illness (jaundice) with HBV, in those <5yr, and those >5yr?

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<5yr, <10%; >5yr, 30-50%

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what is the acute case fatality rate in hepatitis B?

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0.5-1%

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what % of those get chronic infection, in those <5yrs, and those >5yr?

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<5yr, 30-90%, >5yr, 2-10%

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what % have premature mortality from chronic liver disease?

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15-25%

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what are the three biggest risk factors, in order, for hepatits B?

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1) heterosexual sex; 2) injecting drug use; 3) homosexual activity

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what in the serology determines whether a person will recover from hepatisis B or progress to chronic hepatitis B infection?

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whether or not they develop the anti-HBs antibody

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of HBsAg, anti-HBs, and anti-HBc, which are positive during the early (presymptomatic) acute type B hepatitis?

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only HBsAg

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of HBsAg, anti-HBs, and anti-HBc, which are positive during the "window" of HBV infection?

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anti-HBc (IgM)

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of HBsAg, anti-HBs, and anti-HBc, which are positive during acute or chronic type B hepatitis?

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HBsAg, anti-HBc

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of HBsAg, anti-HBs, and anti-HBc, which are positive during recovery from type B hepatitis?

Back 78

anti-HBs, anti-HBc

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of HBsAg, anti-HBs, and anti-HBc, which are positive during immediate recovery phase from type B hepatitis or "low level" carrier state?

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anti-HBc

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of HBsAg, anti-HBs, and anti-HBc, which are positive after immunization with HBsAg?

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anti-HBs

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which can be positive long after hepatitis B infection?

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either anti-HBs or anti-HBc

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in what bodily fluids is HBV in high concentration (3)?

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blood, serum, wounds

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in what bodily fluids is HBV in moderate concentrations (3)?

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semen, vaginal fluid, saliva

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in what bodily fluids is HBV in low levels or not detectable (5)?

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urine, feces, sweat, tears, breast milk

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what is the msot severe consequence of hepatitis B infections due to?

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the presence of the delta agent - a very small, defective RNA virus that requires HBV to cause disease

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what does it increase the likelihood of (2) and how does it increase the likelihood of each?

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1) fulminant hepatitis (with coinfection); 2) chronic active hepatitis (with superinfection)

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***review hepatitis B graphs and charts (outcome by age, serological course)***

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CHRONIC HEPATITIS

Front 91

how long does chronic hepatitis last, and what viruses cause it?

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>6 months, HBV and HCV

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what seems to be happening with the terms used to describe chronic hepatitis?

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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

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what are the current two classes of chronic hepatitis?

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1) non-progressive (persistent); 2) progressive (active)

Front 94

what % of what viruses account for chronic non-progressive (persistent) hepatitis?

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10-12% of HBV, and a proportion of HCV as well

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what is non-progressive (persistent) hepatitis like clinically?

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prolonged, slow recovery without sequelae

Front 96

what lab value changes, and what symptoms does this cause?

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asymptomatic rise in serum transaminase

Front 97

what morphologic changes occur in chronic non-progressive (persistent) hepatitis (2)?

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1) mild inflammation; 2) evidence of hepatocellular degeneration and regeneration

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what appearance often occurs due to the hepatocellular regeneration in non-progressive hepatitis?

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cobblestone appearance

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in what % of hepatitis B and C cases is chronic progressive (active) hepatitis seen?

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in over 25% of hepatitis C, 1-3% of hepatitis B

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in what other condition is it the clinicopathologic finding?

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in autoimmune (lupoid) hepatitis

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what is disease like?

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multiple episodes of mild, often anicteric disease, with increased transaminase

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how can it progress?

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may be symptomatic initially, but may lead to cirrhosis, liver failure, and death

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what is the morphologic pattern of chronic progressive (active) hepatitis?

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bridging necrosis with "piecemeal" necrosis and inflammation

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what is inflamed?

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the limiting plate

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what may or may not be present?

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fibrosis, which may lead to progressive fibrosis and cirrhosis

Front 106

what things are graded when assessing chronic hepatitis severity (3)?

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1) grade of portal inflammatory activity; 2) grade of lobular inflammatory activity; 3) stage of fibrosis

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what is the scale of portal inflammatory activity?

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0 (none) to 4 (severe piecemeal necrosis)

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what is the scale of lobular inflammatory activity?

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0 (none) to 4 ( bridging necrosis)

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what is the scale of fibrosis?

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0 (none) to 4 (cirrhosis)

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HEPATITIS C

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how many genotypes and subtypes are there?

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6 genotypes, >90 subtypes

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what virus family does HCV belong to?

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flaviviridae

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what types of HCV account for 75% of cases in the USA?

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1a and 1b

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how does pathogenicity vary between HCV types?

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all types are equally pathogenic

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what do types 2 and 3 respond better to than type 1?

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alpha interferon

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what is the average incubation period, and incubation period range, for HCV infection?

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average 6-7 weeks, range 2-26 weeks

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what is the acute illness like, and what is the rate?

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mild <20%

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what % have chronic hepatitis?

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70% (most asymptomatic)

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what % go on to cirrhosis?

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10-20%

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what % die from CLD?

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1-5%

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what is the serological course like?

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anti HCV always develops

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what are ALT levels like?

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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

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what % of chronic liver disease is HCV related?

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40-60%

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how many people have chronic HCV infection in the USA?

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2.7 million

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hwo many people die from chronic HCV disease every year?

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8,000 - 10,000

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what is the most common source for HCV infection?

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injecting drug use

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what group has the highest prevalence of HCV?

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hemopheliacs - although transfusions are no longer very dangerous

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what % of IV drug users are infected after 5 years?

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60-90%

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what % of acute cases are transmitted sexually?

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10-20%

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what % of long term partners spread HCV?

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1.50%

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what type of transmission is most efficient?

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male to female

Front 134

what is the risk of transmission from a needle stick?

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1.8% per stick (1/10 HBV)

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what is the rate of perinatal transmission from women HCV-RNA positive at delivery?

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5%

Front 136

when is this rate higher?

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when woman is HIV positive (17%)

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what is the prognosis for infected infants?

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they do well

Front 138

what was it said there is no association with, in perinatal transmission (2)?

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1) breast feeding; 2) delivery method

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how common is severe hepatitis, in perinatal transmission?

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rare

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how common is household transmission of HCV?

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rare, but not absent

Front 141

how could it occur?

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through percutaneous/mucosal exposures to blood (razors, toothbrushes, injections, folk remidies)

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of those who have persistent hepatitis C, how many have stable chronic hepatitis (%)?

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30%

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of the other 70% which have variable (40%) and severe (30%) progression, how many respond to antiviral treatments?

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35% respond, treatment fails in 65%

Front 144

what are factors promoting progression of HCV (4)?

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1) increased alcohol intake; 2) male; 3) over 40 years at time of infection; 4) coinfections (HIV, HBV)

Front 146

HEPATITIS E VIRUS

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what is the incubation period of hepatitis E (average and range)?

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average 40 days, range 15-60 days

Front 149

what is the overall fatality rate?

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1%-3%

Front 150

what group has a higher fatality rate, and what is it?

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pregnant women - 15-25%

Front 151

what other factor increases illness severity?

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age

Front 152

what are chronic sequelae?

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none

Front 153

what are most outbreaks associated with?

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fecally contaminated drinking water

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how do most US cases arise?

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history of travel to HEV endemic areas

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what type of transmission is minimal?

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person to person

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OTHER CAUSES OF HEPATITIS

Front 159

what are other viral causes of hepatitis (4)?

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1) HSV; 2) CMV; 3) adenovirus; 4) EBV

Front 160

what alleles is autoimmune hepatitis associated with (4)?

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HLA alleles - B8, Dr3, Dr52, and Dr4

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what is the therapy (2)?

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prednisone +/- azathioprine (not interferon as opposed to viral hepatitis, may require transplantation)

Front 162

what is the clinical presentation like?

Back 162

quite variable

Front 163

who does type 1 (classic) autoimmune hepatitis typically occur in?

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postmenopausal women

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what may it present as (2)?

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1) infertility; 2) endocrine dysfunction

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what other diseases may it be associated with?

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other autoimmune diseases such as thyroiditis, diabetes, or hemolytic anemia

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what % recover without therapy?

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only 20%

Front 167

what antibodies are notably present (2)?

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hypergammaglobulinemia with a wide variety, but most notably: 1) anti-smooth muscle; 2) ANA

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who does type 2 autoimmune hepatitis often occur in?

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female children (younger than type 1)

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how does it compare to type 1?

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often more aggressive and resistant to therapy than type 1

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what antibody is it associated with?

Back 170

anti-LKM-1 (liver kidney microsomal) rather than anti-smooth muscle

Front 171

what does autoimmune hepatitis look like pathologically?

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like viral chronic active hepatitis

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what is one difference?

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autoimmune hepatitis has more plasma cells in the portal infiltrate

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what other diseases may look similar?

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other autoimmune hepatic diseases such as primary biliary cirrhosis and sclerosing cholangitis

Front 174

what are hints of drug induced liver disease (5)?

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1) disproportionate necrosis; 2) eosinophilia; 3) fatty change; 4) granulomas; 5) disappropriate cholestasis

Front 175

what are example drugs that cause liver damage (4)?

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tylenol, INH, methyldopa, halothane, etc. (the list is long)