03-11 Viral Hepatitis Flashcards

Question 1

Q

OBJECTIVE: Compare and contrast clinical presentation/manifestations of acute vs. chronic hepatitis.

Answer

A

ACUTE

<ul>
<li>Hep A</li>
<li>Hep B
<ul>
<li>> 50% asymptomatic</li>
<li>1% fulminant hepatitis</li>
</ul>
</li>
<li>Hep E
<ul>
<li>Can cause acute liver failure</li>
</ul>
</li>
</ul>

CHRONIC

Symptoms

<ul>
<li>Fatigue</li>
<li>Decreased Exercise Tolerance</li>
<li>Anorexia</li>
<li>Arthralgias</li>
<li>Malaise</li>
<li>Weakness</li>
<li>Depression</li>
</ul>

Hep B

<ul>
<li>Complex Natural hx w/ several phases</li>
<li>May move from high viral load and no dz to active disease to inactive and back</li>
<li>1° adverse outcomes are cirrhosis and HCC</li>
</ul>

Question 2

Q

OBJECTIVE: Describe the pathology of hepatitis.

Question 3

Q

OBJECTIVE: List the causes of hepatitis (including the various viral ones)

Answer

A

VIRAL

<ul>
<li>Hep A-E</li>
<li>M, M, & R</li>
<li>CMV and EBV</li>
<li>Herpes (incl Varicella zoster, i.e. chicken pox)</li>
<li>Adenoviruses</li>
<li>Rarely:  Reovirus, Yellow Feve, Coxsackie B, Echovirus, Marburg Virus, Lassa Fever Virus, Syncytial Giant-cell Hepatitis, Rift Valley Fever</li>
</ul>

Question 4

Q

OBJECTIVE: Describe the virological aspects of Hep A

<ul>
<li>Genome</li>
<li>Family</li>
<li>Transmission</li>
<li>Chronicity</li>
<li>HCC Risk</li>
<li>Causes common in US</li>
<li>Incubation</li>
<li>Diagnosis</li>
<li>Treatment if Exposed</li>
</ul>

Answer

A

<ul>
<li>Genome = RNA</li>
<li>Family = picornavirus</li>
<li>Transmission = water (i.e. fecal to oral)</li>
<li>Chronicity = acute only, but may trigger chronic AIH</li>
<li>HCC Risk = none</li>
<li>Causes in US
<ul>
<li>most cases from int'l travel</li>
<li>10% household contact</li>
<li>9% MSM</li>
<li>7% Food  (usu shellfish) or waterborne outbreaks</li>
<li>3% Daycare child or employee- 3%</li>
<li>3% IV drug use</li>
</ul>
</li>
<li>Incubation: avg 30 days (shorter than HBV and HCV)
<ul>
<li>1 wk prodrome of feeling shitty, anorexia + RUQ</li>
</ul>
</li>
<li>Diagnosis: sx PLUS (+) anit-HAV IgM
<ul>
<li>Liver zymes usu > 1000</li>
<li>jaundice less likely in kids</li>
</ul>
</li>
<li>Tx if exposed:
<ul>
<li>Give HAV vacc</li>
<li>Give Ig to:
<ul>
<li>infants</li>
<li>eldery</li>
<li>immuncomp</li>
<li>chronic liver dz</li>
</ul>
</li>
</ul>
</li>
</ul>

Question 5

Q

OBJECTIVE: Describe the virological aspects of Hep B

<ul>
<li>Genome</li>
<li>Family</li>
<li>Life Cycle</li>
<li>Transmission</li>
<li>Incubation period</li>
<li>Chronicity</li>
<li>HCC Risk</li>
</ul>

Answer

A

<ul>
<li>Genome = partial dsDNA(only DNA hep virus)

<ul>
<li>open reading frames, partially overlap, encode:</li>
<li>Viral envelope (pre-S1, preS2 and S)</li>
<li>Core pre-C (= HbeAg anitgen, directs prods to ER, ?part of immune tolerance) and C (=HbcAg, assembles into capsid)</li>
<li>DNA Polymerase (P)</li>
<li>X protein: fucks w/ p53→ ?HCC</li>
</ul>
</li>
<li>Family = Hepadnaviridae</li>
<li>Life Cycle
<ol>
<li>receptor mediated endocytosis</li>
<li>uncoats and goes into nucleus</li>
<li>Viral DNA pol turns genome into cccDNA (covalently closed circular)</li>
<li>Host RNA pol transcribes
<ul>
<li>HbeAg made, directy products to golgi for assembly and exocytosed by itself</li>
</ul>
</li>
<li>viral RT pol uses that RNA to make (-) DNA for new virus</li>
<li>assembles: virions, and decoys (filaments and spheres w/ only HbsAg) and goes out</li>
</ol>
</li>
<li>Transmission = blood/bodily fluids
<ul>
<li>vertical (mom-> baby)</li>
<li>horizontal: child-to-child, unsafe injections or transfusions, or sex</li>
<li>100X more infectious > HIV</li>
<li>super common (5-20%) in "Asia/Africa"</li>
</ul>
</li>
<li>Incubation period: at least 6wks, up to 6 mos</li>
<li>Chronicity = can be chronic
<ul>
<li>Much more likely the younger you are</li>
<li>~90% of infants will develop carrier state</li>
</ul>
</li>
<li>HCC Risk = yes</li>
</ul>

Question 6

Q

Extrahepatic mechanisms of HBV

Answer

A

<ul>
<li>Rash</li>
<li>Arthritis</li>
<li>Angioneurotic edema</li>
<li>GN</li>
<li>Vasculitis</li>
</ul>

Question 7

Q

OBJECTIVE: Describe the virological aspects of Hep C.

<ul>
<li>Virus</li>
<li>Genome</li>
<li>Family</li>
<li>Transmission</li>
<li>
Life Cycle
</li>
<li>
Dx
</li>
<li>Chronicity</li>
<li>HCC Risk</li>
</ul>

Answer

A

<ul>
<li>Virus = HCV, 6 genotypes
<ul>
<li>no ∆ in virulence</li>
<li>just susceptible to diff tx</li>
</ul>
</li>
<li>Genome = ssRNA, unenveloped</li>
<li>Family = Flaviviridae</li>
<li>Transmission = blood</li>
<li>Life Cycle = cytoplasmic
<ol>
<li>receptor-mediated endocytosis</li>
<li>ssRNA traslated by RER ribos into 1 polyprotein</li>
<li>proteases</li>
<li>bud through ER → secreted from cell</li>
</ol>
</li>
<li>Dx: anti-HCV Ab ELISA; f/u w/ PCR for HCV RNA if (+)</li>
<li>Chronicity = yes, > 75%</li>
<li>HCC Risk = yes</li>
</ul>

Question 8

Q

Extrahepatic manifestations of HCV

<ul>
<li>Heme</li>
<li>Renal</li>
<li>Derm</li>
<li>Vasc</li>
</ul>

Answer

A

Hematologic

<ul>
<li>Cryoglobulinemia</li>
<li>Aplastic anemia</li>
<li>Thrombocytopenia</li>
<li>B-cell lymphoma?</li>
</ul>

Renal

<ul>
<li>Memebranoprolif GN</li>
<li>Nephrotic syndrome</li>
</ul>

Derm

<ul>
<li>Porphyria Cutanea Tarda</li>
<li>Lichen planus</li>
<li>Leukocytoclastic vasculitis (part of cryo spectrum)</li>
</ul>

Vascular

<ul>
<li>Polyarteritis nodosa</li>
<li>Endocrine</li>
<li>Glucose intolerance (gen 1)</li>
</ul>

Question 9

Q

Who should be screened for HCV?

Answer

A

<ol>
<li>All people born between 1945 and 1965</li>
<li>Pts w/ abnl LFTs</li>
<li>
Other pts w/ risk factors:
</li>
</ol>

<ul>
<li>IVDU, I.N. cocaine or unsterile tattoes (even if just once)</li>
<li>Viral infxs w/ same risks, HIV, HBV</li>
<li>Needle stick or mucosal exposure to HCV-(+) blood</li>
<li>Transfusions or organ Transplant before July 1992
<ul>
<li>Hemophilia receiving clotting factor concentrates prior to 1987</li>
</ul>
</li>
<li>Hx of hemodialysis</li>
<li>Intimate contact
<ul>
<li>Children born to HCV-infected mom ( 4.3 to 7.1%)</li>
<li>Sexual partners of HCV-(+) pts (rare)
<ul>
<li>Higher if you have another skin-breaking STI </li>
</ul>
</li>
</ul>
</li>
</ul>

Question 10

Q

Treatment of Hep C

Answer

A

Genotypes 1 & 4

<ul>
<li>Sofosbuvir + Peg-INF + ribavirin X 12 wks</li>
<li>Cure rate = 92% (80% if already cirrhotic)</li>
</ul>

Genotype 2

<ul>
<li>Sofosbuvir + ribavirin X 12 wks</li>
<li>Cure rate = 92%</li>
</ul>

Genotype 3

<ul>
<li>Sofosbuvir + ribavirin X 24 wks</li>
<li>Cure rate = 85%</li>
</ul>

Sofosbuvir costs $1000 per pill!!!!

Question 11

Q

OBJECTIVE: Describe the virological aspects of Hep D

<ul>
<li>Genome</li>
<li>Family</li>
<li>Transmission</li>
<li>Chronicity</li>
<li>HCC Risk</li>
<li>Tx</li>
</ul>

Answer

A

<ul>
<li>Genome = Defective RNA (needs HBV)</li>
<li>Family = none, satellite virus</li>
<li>Transmission = blood
<ul>
<li>coinfected (pt gets both HBV and HDV at same time)</li>
<li>superinfected (pt gets HDV later after developing chronic HBV)</li>
</ul>
</li>
<li>Chronicity = yes</li>
<li>HCC Risk = yes</li>
<li>Interferon only option, follow [HDV DNA]</li>
</ul>

Question 12

Q

OBJECTIVE: Describe the virological aspects of Hep E

<ul>
<li>Epidemiology</li>
<li>Genome</li>
<li>Family</li>
<li>Transmission</li>
<li>Incubation</li>
<li>Chronicity</li>
<li>HCC Risk</li>
<li>Dx</li>
</ul>

Answer

A

<ul>
<li>More common in developing countries but surprisingly common here
<ul>
<li>Don't just think of it as DDx for those who went to endemic areas</li>
</ul>
</li>
<li>Genome = RNA (similar to HAV)</li>
<li>Family = Calciviridae</li>
<li>Transmission = water (i.e. fecal to oral) (similar to HAV)
<ul>
<li>pig resevoir (undercooked pork, effluent)</li>
<li>50% vert trans to baby</li>
</ul>
</li>
<li>Incubation = 2-9 wks (similar to HAV)</li>
<li>Chronicity = yes, in immunosuppressed</li>
<li>HCC Risk = no</li>
<li>Dx = Acute HEV IgM, or HEV DNA; Past exposure HEV IgG</li>
</ul>

Can cause acute liver failure

<ul>
<li>May be misdiagnosed as drug toxicity or unexplained decompensation in  cirrhotiic</li>
</ul>

Hep A and Hep E are the only water-borne viral hepaitides and the only ones w/o risk of HCC

Question 13

Q

OBJECTIVE: List the various serologic tests used to diagnose viral hepatitis A-E. Explain how they are used and what they define

Answer

A

Hep A

Hep B (see image here): if you only get one test, get Core

<ul>
<li>HBsAg:First marker of active infection (before ALT and sx); very specific</li>
<li>Anti-HBs (Surface)
<ul>
<li>protective Ab showingimmunity</li>
<li>appears after HBsAg disappears</li>
<li>vaccination gives you (+) Anti-HBs</li>
</ul>
</li>
<li>Anti-HBc (Core)
<ul>
<li>IgM: acute infection, still (+) during window phase or reactivation</li>
<li>IgG: hx of active infx (i.e. not (+) from immunization)</li>
</ul>
</li>
<li>HBeAg
<ul>
<li>Means you have actively replicating HBV</li>
<li>Appears w/ or soon after HBsAg</li>
<li>Loss = nonreplicative phase or replicative mutant</li>
</ul>
</li>
<li>Anti-HBe
<ul>
<li>appears after loss of active replication (seroconversion)</li>
</ul>
</li>
<li>HBV DNA
<ul>
<li>Best marker of replicative stage</li>
<li>Found in serum in active infection</li>
<li>May be present after pt “immune”</li>
</ul>
</li>
<li>Anti-HDV
<ul>
<li>(+) IgM = coinfection</li>
<li>(+) IgG = superinfection</li>
</ul>
</li>
</ul>

Hep C

Hep D

Hep E

Question 14

Q

OBJECTIVE: Compare and contrast the viral activity and the host response in the immunocompetent vs immunodeficient state.

Question 15

Q

OBJECTIVE: Describe the clinical outcomes of chronic hepatitis

Answer

A

(including cirrhosis and risk of hepatocelluar carcinoma)

Question 16

Q

OBJECTIVE: What vaccines and other preventative measures are there for viral hepatitis?

Question 17

Q

OBJECTIVE: Describe/define fulminant hepatic failure

Question 18

Q

Dx here? Why?

Answer

A

HBV, ground glass appearance (arrow) near pathognomonic

Question 19

Q

Hep

Answer

A

Acute hepatitis pattern w/ significant lobular inflammation,ballooned hepatocytes and apoptotic (Councilman) bodies (arrow) (H&E, 400X)

<ul>
<li>Due to Hep B here</li>
<li>Not sure if this would look different w/ other hep viruses</li>
</ul>

Question 20

Q

Fill in this table (see slide 42 if too small)

Answer

A

See answers on slide 43 if too small

Question 21

Q

What should you screen pts w/ chronic HBV for? How often?

Answer

A

Question 22

Q

At what stage of infection do you tx for HBV?

Two best meds?

Answer

A

Treat at

<ul>
<li>acute phase</li>
<li>HBeAg (+) phase</li>
<li>HBeAb (+) (i.e. seroconverted pts) who have reactivation</li>
</ul>

Two best meds

<ol>
<li>entecavir</li>
<li>tenofovir</li>
</ol>

Question 23

Q

Which of the following Regarding HAV are True?

<ol>
<li>24 year old female develops acute Hepatitis 3 months after going to India. You tell her she likely has HAV</li>
<li>32 year old with acute hepatitis Serologies are drawn anti-sAg+, anti-HAV IgM+ you dx HAV</li>
<li>50 year old Dart prof with HCV ab+ antiHAV ab(-) wants to go to central America. You strongly recommend Vaccination</li>
</ol>

Answer

A

<ol>
<li>False</li>
<li>True</li>
<li>True</li>
</ol>

Question 24

Q

Which of the following are true?

<ol>
<li>Pts with active HBV have a higher risk of sexual transmission than HAV, HIV or HCV</li>
<li>Increasing age results in increasing risk of chronic infection</li>
<li>Patients with HBV should not share food, drink from same glass or kiss their children</li>
</ol>

Answer

A

<ol>
<li>True</li>
<li>False, younger age is more likely to develop chronic infx</li>
<li>False, just don't share razors, toothbrushes, semen, blood, sperm</li>
</ol>

Question 25

Q

Which of the following are true?

<ol>
<li>HBV is a DNA virus with a very unique and fascinating life cycle</li>
<li>HBsAg + is diagnostic for HBV infection</li>
<li>HBcAb IgM is diagnostic for acute HBV§HBsAb is diagnostic for a past infection</li>
<li>A very high level of HBV DNA indicates a very aggressive infection which requires immediate treatment</li>
<li>A 50 year old Asian male with HBV and no cirrhosis is at risk for liver cancer</li>
</ol>

Answer

A

<ol>
<li>True</li>
<li>True</li>
<li>True</li>
<li>False</li>
<li>True</li>
</ol>

Question 26

Q

Which of the following statements about HCV lifecycle are true?

<ol>
<li>HCV risk  has decreased from 3-5% to 1 to 100,000 per transfusion since 1992</li>
<li>HCV is an aggressive disease which can lead to cirrhosis in 20-30% within 5 years</li>
<li>HCV is the leading cause of liver cancer and leading indication for liver transplantation in the US</li>
</ol>

Answer

A

<ol>
<li>true</li>
<li>false</li>
<li>true</li>
</ol>

Question 27

Q

Which of the following are incorrect?

<ol>
<li>HCV-Ab+ is diagnostic for active HCV infection</li>
<li>Baby boomers (birth 1945-165) should be screened for HCV even if no risk factors</li>
<li>Sexual transmission is a signficant risk factor for HCV</li>
<li>IV Drug abuse with shared needles is a significant cause of HCV transmission</li>
</ol>

Answer

A

<ol>
<li>False, HCV-Ab could be positive in person w/ prior cleared HCV infc. Need to get PCR of HCV RNA (gold std) to verify.</li>
<li>True, this generation has the highest prevalence and USPSTF recommends screening erryone</li>
<li>False, not a significant risk factor, but can happen rarely</li>
<li>True</li>
</ol>

Question 28

Q

True or False?

<ol>
<li>HCV infection can be suppressed but never eradicated</li>
<li>The cure rate for HCV is <50% if the viral load is high</li>
<li>The cure rate for HCV now is > 80% regardless of genotype viral load or race</li>
<li>Cure of Hepatitis C can result in regression of fibrosis and improved clinical outcomes</li>
</ol>

Answer

A

<ol>
<li>False!</li>
<li>False!</li>
<li>True</li>
<li>True</li>
</ol>

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03-11 Viral Hepatitis Flashcards

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