03-11 Viral Hepatitis

Question 1

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

Answer 1

<p>ACUTE</p>

<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>

<p>CHRONIC</p>

<p>Symptoms</p>

<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>

<p>Hep B</p>

<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&deg; adverse outcomes are cirrhosis and HCC</li>
</ul>

<p>&nbsp;</p>

Question 2

<p>OBJECTIVE: Describe the pathology of hepatitis.</p>

Answer 2

<p>.</p>

Question 3

<p>OBJECTIVE: List the causes of hepatitis (including the various viral ones)</p>

Answer 3

<p>VIRAL</p>

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

Question 4

<p>OBJECTIVE: Describe the virological aspects of Hep A</p>

<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 4

<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&#39;l travel</li>
<li>10% household contact</li>
<li>9% MSM</li>
<li>7% Food&nbsp; (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

<p>OBJECTIVE: Describe the virological aspects of Hep B</p>

<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 5

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

<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><strong>Family</strong> = Hepadnaviridae</li>
<li><strong>Life Cycle</strong>
<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><strong>Transmission</strong> = 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><strong>Incubation period: </strong>at least 6wks, up to 6 mos</li>
<li><strong>Chronicity</strong> = 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><strong>HCC Risk</strong> = yes</li>
</ul>

Question 6

<p>Extrahepatic mechanisms of HBV</p>

Answer 6

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

Question 7

<p>OBJECTIVE: Describe the virological aspects of Hep C.</p>

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

Answer 7

<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&nbsp;&rarr; 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

<p>Extrahepatic manifestations of HCV</p>

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

Answer 8

<p><strong><span>Hematologic</span></strong></p>

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

<p><strong><span>Renal</span></strong></p>

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

<p><strong><span>Derm</span></strong></p>

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

<p><strong>Vascular</strong></p>

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

Question 9

<p>Who should be screened for HCV?</p>

Answer 9

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

Question 10

<p>Treatment of Hep C</p>

Answer 10

<p>Genotypes 1 &amp; 4</p>

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

<p>Genotype 2</p>

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

<p>Genotype 3</p>

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

<p><strong>Sofosbuvir costs $1000 per pill!!!!</strong></p>

Question 11

<p>OBJECTIVE: Describe the virological aspects of Hep D</p>

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

Answer 11

<ul>
<li>Genome = <u><strong>D</strong></u>efective 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

<p>OBJECTIVE: Describe the virological aspects of Hep E</p>

<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 12

<ul>
<li>More common in developing countries but surprisingly common here
<ul>
<li>Don&#39;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><strong>pig resevoir</strong>&nbsp;(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 =&nbsp;Acute HEV IgM, or HEV DNA; Past exposure HEV IgG</li>
</ul>

<p><strong>Can cause acute liver failure</strong></p>

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

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

Question 13

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

Answer 13

<p>Hep A</p>

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

<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>

<p>Hep C</p>

<p>Hep D</p>

<p>Hep E</p>

Question 14

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

Answer 14

<p>.</p>

Question 15

<p>OBJECTIVE: Describe the clinical outcomes of chronic hepatitis </p>

Answer 15

<p>(including cirrhosis and risk of hepatocelluar carcinoma)</p>

Question 16

<p>OBJECTIVE: What vaccines and other preventative measures are there for viral hepatitis?</p>

Answer 16

<p>.</p>

Question 17

<p>OBJECTIVE: Describe/define fulminant hepatic failure</p>

Answer 17

<p>.</p>

Question 18

<p>Dx here? Why?</p>

Answer 18

<p>HBV, ground glass appearance (arrow) near pathognomonic</p>

Question 19

<p>Hep</p>

Answer 19

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

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

Question 20

<p>Fill in this table (see slide 42 if too small)</p>

Answer 20

<p>See answers on slide 43 if too small</p>

Question 21

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

Answer 21

<ul>
<li>AFP + U/S q6-12mo</li>
</ul>

Question 22

<p>At what stage of infection do you tx for HBV?</p>

<p>Two best meds?</p>

Answer 22

<p>Treat at</p>

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

<p>Two best meds</p>

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

Question 23

<p>Which of the following Regarding HAV are True?</p>

<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 23

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

Question 24

<p>Which of the following are true?</p>

<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 24

<ol>
<li>True</li>
<li>False, younger age is more likely to develop chronic infx</li>
<li>False, just don&#39;t share razors, toothbrushes, semen, blood, sperm</li>
</ol>

Question 25

Which of the following are true?

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

Answer 25

1. True
2. True
3. True
4. False
5. True

Question 26

Which of the following statements about HCV lifecycle are true?

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

Answer 26

1. true
2. false
3. true

Question 27

Which of the following are incorrect?

1. HCV-Ab+ is diagnostic for active HCV infection
2. Baby boomers (birth 1945-165) should be screened for HCV even if no risk factors
3. Sexual transmission is a signficant risk factor for HCV
4. IV Drug abuse with shared needles is a significant cause of HCV transmission

Answer 27

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

Question 28

True or False?

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

Answer 28

1. False!
2. False!
3. True
4. True