Term
True or False:
Transmission of blood-borne pathogens is most likely when infection is not clinically apparent. |
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Definition
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Term
| What are the associated risks of infection from a needle stick infected with HBV, HCV and HIV? |
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Definition
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Term
| How is prevention of blood-borne pathogen transmission achieved? |
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Definition
1) Screening of blood products for Ab and NAT
2) Testing for surrogate markers of hep B (ALT)
3) Pre-secrening interviews to identify risk
4) Hep B vaccination |
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Term
| Other than the 6 major hepatitis viruses, how else can systemic hepatitis infection occur? |
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Definition
1) CMV
2) EBV
3) Yellow fever
4) Dengue |
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Term
| When is the only situation where you might see HDV? |
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Definition
| Co-infection or super-infection with HBV |
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Term
| Which forms of viral hepatitis have available therapeutic options? |
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Definition
1) HBV (IFN and Lamivudine)
2) HCV (IFN and Ribavirin) |
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Term
| Which forms of viral hepatitis have Parenteral transmission? |
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Definition
1) HBV (also sexual and perinatal)
2) HCV
3) HDV
4) HGV (also sexual and parinatal) |
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Term
| Which forms of viral hepatitis have fecal-oral transmission? |
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Definition
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Term
| Which forms of viral hepatitis have ssRNA (+) genomes? |
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Definition
1) HAV (Picornavirus/unenveloped)
2) HCV (Flavivirus/enveloped)
3) HEV (Calicivirus/un-enveloped)
4) HGV (Flavivirus/enveloped) |
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Term
| Which two viral hepatitis forms are Flaviviruses? |
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Definition
| HCV (enveloped ssRNA (+) ) and HGV |
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Term
| Which form of viral hepatitis have (-) RNA genomes? |
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Definition
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Term
| Which form of viral hepatitis has an incomplete dsDNA genome? |
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Definition
HBV (hepatdnavirus- circular genome)
Treat with IFN and Lamivudine |
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Term
| Which form of viral hepatitis are most likely to cause chronic infection? |
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Definition
1) HBV is 2-10% with 90% in neonates
2) HCV is 70-90%
3) HDV (with HBV) |
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Term
| Rank the severity of viral hepatitis infections from severe to mild. |
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Definition
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Term
| Which form of viral hepatitis are worrisome for liver cancer (HCC)? |
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Definition
BCD for cancer!
1) HBV-Hepatna, dsDNA
2) HCV-Flavivirus, ssRNA (+)
3) HDV-ssRNA(-)) |
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Term
| Which forms of viral hepatitis should be treated with antibiotic prophylaxis? |
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Definition
1) HAV (HAIG and vaccine)
2) HBV (HBIG and vaccine)
3) HDV (HBV vaccine) |
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Term
| Explain the genomic structure of HBV |
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Definition
1) Incomplete dsDNA circular genome
2) 4 genes (Surface, Core, Pol, X) |
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Term
| Explain the pathogenesis of HBV infection. |
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Definition
1) Entry via blood/intimate contact/birth
2) Replication in liver (Kupffer cells, hepatocytes)
3) 80% subclinical, 20% acute hepatitis with jaundice, rare Fulminant hepatitis (severe)
4) Hepatocyte damage due to IMMUNOPATHOGENESIS
5) 90-98% clear infection, while 2-10% persists in adults and 90% in kids.
6) Most (90%) are asymptomatic carriers, but some can develop Cirrhosis or Hepatocellular carcinoma (HCC) |
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Term
| How do you diagnose a case of HBV? |
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Definition
1) Liver enzymes (ALT, AST) as markers of liver damage
2) Circulating HBV DNA in blood by PCR (ongoing viral replication)
3) HBV serology (S and C and E antigens and accompanied antibodies) |
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Term
| How do you diagnose an acute vs. chronic case of HBV? |
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Definition
KEYS
HBsAg will persist in chronic infection
anti-HBsAg will only be seen if immunity exists
1) If HBsAg is persistent after acute infection, it is chronic
2) HBeAg (pre-core antigen) is a sign of ongoing HBV replication and is associated with infectivity
3) Anti-HBs indicates immunity to HBV
4) Anti-HBc indicates previous or current HBV infection and is seen in chronic infection
5) Anti-Hbc is variable |
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Term
| What virulence factors are associated with HBV? |
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Definition
1) Ability to establish chronic infection
2) HBsAg as immune decoy
3) HBx protein- transcriptional activator that may lead to HPCC |
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Term
| How do you treat/prevent HBV infection? |
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Definition
1)
-If acute, HBIG in unvaccinated youth or exposed infants
-If chronic, PEG-IFN-alpha and Lamivudine (or Tenofovir and Entecavir)
- for cirrosis and end-stage liver disease, perform liver transplantation with aggressive Lamivudine treatment.
2) Prevent with recombinant HBsAg vaccine (initial injection with 2 boosters) is routine for infants and adolescents. |
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Term
| How is HDV a unique case of viral hepatitis? |
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Definition
HDV is a defective RNA virus that needs HBV for infection and is prevalent among injection drug users, causing more severe acute and chronic cases.
- "Virus-like" particle contains RNA and delta Ag, enveloped within an HBV envelope (HBsAg)
- RNA has "Self-cleaving" and "self-ligating" capabilities. |
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Term
| How do you diagnose/treat HDV? |
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Definition
1) Serology for delta Ag
2) HBV vaccine, IFN-a and Liver transplant |
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Term
| How does HCV present in the blood? |
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Definition
-As heterogeneous "quasispecies," with multiple sequence isolates at any one time arising from diversity if hv region of envelope gene (IMMUNE ESCAPE).
- 6 different genotypes, but 1 is common in US |
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Term
| What are the most likely outcomes of HCV infection? |
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Definition
1.5% of US population is infected and is #1 indicator for liver transplant.
1) 80-90% have persistent chronic viral infection
2) 10-20% develop chronic hepatitis (risk for cirrhosis and HCC)
3) Associated with immune-meiated Cryoglobulinemia |
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Term
| What is Cryoglobulinemia? |
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Definition
| Immune-mediated disease associated with chronic HCV. |
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Term
| What virulence factors are associated with HCV? |
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Definition
1) High mutation rate
2) Protease blocks immune activation of infected cell. |
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Term
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Definition
1) Serology for anti-HCV Ab
2) RT-PCR for circulating virus |
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Term
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Definition
1) PEG-IFN-a and Ribavirin (IL28B genotype predicts responsiveness)
2) Protease inhibitors (Boceprevir and Telaprevir) added to standard therapy.
3) No prophylaxis with IG or vaccine |
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Term
| Why are transplant infection risks called "Iatrogenic"? |
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Definition
| They are caused by physicians who give immunosuppressive drugs. |
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Term
| Which latent infections are of primary concern for reactivation after transplantation? |
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Definition
1) Latent HSV
2) re-infection with HBV or HCV (if transplant for HBV or HCV)
3) Trypanosoma cruzi (Chagas disease) |
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Term
| Which donor-organ associated pathogens are considered clinically relevant? |
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Definition
1) Prion disease
2) CMV
3) EBV
4) T. cruzi |
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Term
True or False:
More severe disease is associated with secondary HSV reactivation following transplant than primary HSV |
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Definition
False!
Primary is more serious. |
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Term
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Definition
DNA virus in herpesvirus family that infects B cells via CD21 (CR2) or nasopharyngeal cells by CD21-liker receptor.
Can establish LATENCY and IMMORTALIZE B cells
1) Primarily by saliva
2) Replication in pharyngeal epithelium or tonsillar B cells
3) Spread by blood
4) Infect B lymphocytes and sets up latent infection
5) CTL recognize latent EBV and eliminate most of them
6) During latency, only EBNA-1 antigen is produced, which cannot be presented by MHC-1
7)PTLD arises from lack of CTL recognition of latent EBV in immunosuppressed hosts. |
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Term
| How does PTLD occur in immunosuppressed patients with latent EBV? |
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Definition
During latency, only EBNA-1 antigen is produced, which cannot be presented by MHC-1
PTLD arises from lack of CTL recognition of latent EBV in immunosuppressed hosts. |
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Term
| What is the clinical presentation of EBV infection? |
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Definition
1) Acute infection causes IM
2) Chronic can cause cancer, as well as post-transplant lymphoproliferative disease (PTLD) of B cells, which can cause lymphoma. |
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Term
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Definition
No culture!
1) Acute- monospot test for Ab against EBV and microscopy for atypical lymphocytosis
2) Recent or past infection- detect anti-EBV Ab (anti-early antigen, anti-viral capsid antigen, anti EBNA)
3) PTLD- qPCR to determine EBV load to identify patients at risk and Biopsy to confirm. |
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Term
| What prevention/treatment options are available for EBV |
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Definition
No vaccine or acute treatment available!
1) PTLD- decrease immunosuppressive therapy to allow CTL response!
2) Acyclovir and Ganciclovir are OK against EBV during replication, but NOT FOR LATENCY.
3) Immune therapy (CTL in bone marrow transplant patients or Rituximab). |
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Term
| How is HBeAg clinically relevant? |
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Definition
| Sign of ongoing HBV replication= transmission risk |
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Term
| Explain the difference in diagnostic profiles between Anti-HBc Ag and Anti-HBs AGg in HBV infection. |
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Definition
Anti-HBc Ag will be seen in chronic HBV, but not in vaccinated individuals.
Anti-HBs Ag will not be seen in chronic HBV, but will be found in vaccinated individuals. |
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Term
| How is HCV treatment an example of personalized medicine? |
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Definition
| The IL-28B genotype is predictive of response to INF-a/Ribavirin therapy effectiveness. |
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Term
| How does HBV compare to HCV in terms of transmissability, acute infection, chronic cirrosis and HCC? |
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Definition
1) B is more transmissible (30% vs. 3% of blood exposures)
2) B presents acutely, but C will not
3) C is a more common cause of cirrhosis and HCC. |
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Term
| Who is under particularly high level of risk for latent EBV reactivation? |
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Definition
1) Immunosuppressed post-transplant
2) EBV-naive recipient |
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