Hepatitis Viruses Flashcards by Danielle Himelfarb

What are laboratory indications of liver failure/liver inflammation?

Elevated AST or ALT

Increased prothrombin time or INR

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What is the definition of hepatitis?

Inflammation of liver which can lead to damage and potentially liver dysfunction

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What are classic signs and symptoms of acute hepatitis?

Fatigue, nausea, vomiting, malaise, headache, chills
Abdominal pain (RUQ), loss of appetite
Chalky stools
Jaundice and icterus (bilirubin in skin & sclerae)

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Is hepatitis B a RNA or DNA virus?

DNA virus (hepadnavirus)

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What are the different core antigens of Hepatitis B?

Core antigen HBcAg

e antigen HBeAg

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What is the e antigen of Hepatitis B?

Role not well characterized

Acts as an indicator of active viral replication and increased transmissibility

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What is the surface antigen of Hepatitis B?

HBsAg - forms viral component of lipoprotein envelope

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What is cccDNA?

Covalently closed circular DNA (tightly supercoiled)

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What is the life cycle of HBV?

Binds via surface antigen
Uncoats into cytoplasm
Nucleocapsids release ‘relaxed’ circular DNA (rcDNA) into nucleus
rcDNA is repaired to yield cccDNA (covalently closed circular DNA)
cccDNA is transcribed to 4 viral mRNA
- Smaller mRNAs transplated into structural proteins
- Larger mRNA packaged with RT into core particle
- Larger mRNA is finally transcribed by reverse transcriptase into negative strand DNA
Virion can then be released

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How long does cccDNA persist in host?

Indefinitely, never removed completely from nuclei of host

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What causes the liver damage associated with Hepatitis B?

Immune response (primarily cytotoxic T cell response) to viral antigens expressed on hepatocyte cell surface

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How many genotypes are there of Hep B?

8 (A-H)

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What are modes of HBV transmission?

Sexual, parenteral, perinatal

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What body fluids have highest concentration of Hep B virus?

Blood, serum, wound exudates

Semen, vaginal fluid, saliva are moderate

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What age will show clinical symptoms of Hep 5?

Usually > age 5

Under age 5 don’t have a fully functional immune system, and immune response is what causes clinical presentation

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What age is more likely to develop chronic infection from acute infeciton?

Usually < age 5
Immune system is not fully developed and cannot fight off disease as well
(>90% of children progress to chronic, <5% of adults)

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What are the different serologic markers of Hepatitis B?

HBsAg
HBeAg
Anti-HBs
Anti-HBe
Anti-HBc (IgM)
Anti-HBc (IgG)
HBV DNA

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What is the definition and clinical use of HBsAg?

Hepatitis B surface antigen
General marker of infection
First serologic marker to appear
Persistence for >6 months = chronic infection

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What is the definition and clinical use of HBeAg?

Hepatitis B e antigen

Indicates active replication of virus

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What is the definition and clinical use of Anti-HBs?

Antibody to hepatitis B surface antigen
Indicates recovery from natural infection and/or immunity
Detectable after Hep B immunization

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What is the definition and clinical use of Anti-HBe?

Antibody to hepatitis B e antigen
Marker of reduced level of replication
Not often done in acute evaluation

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What is the definition and clinical use of Anti-HBc (IgM)?

Antibody to hepatitis B core antigen

Marker of current acute hepatitis B infection

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What is the definition and clinical use of Anti-HBc (IgG)?

Antibody to hepatitis B core antigen

Marker of current or past infection

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What is the definition and clinical use of HBV DNA?

Hepatitis B virus genomic DNA
Marker of HBV replication
Used for monitoring response to therapy

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What is the first serologic marker of HBV to appear?

HBsAg

Can you ever see expression of HBsAg and anti-HBs serologic markers at the same time?

No, there is window period between these two

What is serologic profile of someone with an active acute Hepatitis B infection?

``` HBsAg POSITIVE Anti-HBs NEGATIVE Anti-HBc (IgM) POSITIVE Anti-HBc (IgG) NEGATIVE HBV DNA POSITIVE ```

What is serologic profile of someone with a resolved Hepatitis B infection?

``` HBsAg NEGATIVE Anti-HBs POSITIVE Anti-HBc (IgM) NEGATIVE Anti-HBc (IgG) POSITIVE HBV DNA NEGATIVE ```

What is serologic profile of someone who developed chronic Hep B disease?

``` HBsAg POSITIVE (at least 6 months apart) Anti-HBs NEGATIVE Anti-HBc (IgM) NEGATIVE Anti-HBc (IgG) POSITIVE HBV DNA POSITIVE ```

What is a key group of individuals who should be screened for Hep B?

Persons born in countries with >2% HBsAg prevalence (endemic areas)

What serologic marker will be detectable after HBV immunization?

Anti-HBs

Who receives treatment for HBV?

Patients who have evidence of liver damage (elevated ALT or significant fibrosis/inflammation) Usually treat indefinitely

What is the major treatment endpoint?

Reduction of HBV DNA

What is the most common therapy for HBV?

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) (Usually tenofovir or entecavir)

What options are available for hepatitis B prevention?

Hepatitis B immunoglobulin | Hepatitis B vaccine

What is unique about Hepatitis D?

Requires co-infection with Hepatitis B

How is diagnosis of Hepatitis D made?

Serology | Anti-HDV IgM (acute) or IgG (chronic)

``` What is the diagnosis of this serologic profile? Anti-HCV positive Anti-HBs positive Anti-HBc (IgG) positive HBsAg negative Anti-HAV negative ```

Chronic hepatitis C with resolved HBV

Is Hepatitis C a RNA or DNA virus?

RNA

How many genotypes are there of Hepatitis C?

7 genotypes (1-7)

What is unique about the life cycle of HCV?

All occurs outside of the nucleus | Uses host proteases and host cellular membranes to form membranous web on ER where RNA replication occurs

What is the main target of HCV therapies?

Non-structural proteins (protease, polymerase, NS5A)

How do HCV virions get released from the cell cytoplasm?

Uses lipid secretion pathways

Why do more people progress to chronic infection with HCV than with HBV?

HCV is highly mutagenic | Harder to develop strong immune response --> more likely to progress to chronic

What cell does HCV primarily infect?

Hepatocytes

What is the function of HCV NS3-4A core protein?

Blunts host innate immune response to virus

What causes liver damage in Hep C infection?

Immune response (cytotoxic T cells), not the direct cytopathic effect of virus

What liver disease can cause hepatocellular carcinoma?

Hep B, Hep C, chronic alcoholism

What are modes of transmission of HCV?

IDU > Sexual > Transfusion

When will symptoms of HCV develop?

Acute infection - Usually asymptomatic Chronic infection - May be asymptomatic for years Symptoms may not be present until cirrhosis develops

What is the most important factor associated with disease progression in HCV?

Alcohol

Is HCV viral load associated with disease progression?

How is HCV diagnosed?

ELISA screening for HCV antibodies | Confirmed with HCV viral load

Who receives treatment for HCV?

Based on degree of liver damage | Evidence of fibrosis (stage 2 or higher) on liver biopsy

What is the standard of care for therapy for HCV?

Moving away from Inferferon regimens | Now using protease inhibitors, polymerase inhibitors, and NS5A inhibitors

What is the goal of therapy of HCV?

Attain sustained virologic response (SVR) - undetectable viral load 3-6 months after therapy completion Is essentially a CURE

What drugs are the mainstays of treatment for HCV?

Sofosvuvir - NS5B inhibitor Simeprevir - NS3-4A protease inhibitor Ledipasvir - NS5A inhibitor

What is the diagnosis of these labs and seroglogic profile? Labs: elevated ALT/AST, elevated prothrombin and INR Anti-HCV positive Anti-HBc negative (IgM and IgG) HBsAg negative Anti-HBs positive Anti-HAV (IgM) positive

Hepatitis A | theoretically could be HCV but overwhelming majority of those patients are not symptomatic

Is Hepatitis A an RNA or DNA virus?

RNA

What is the mode of transmission of Hepatitis A?

Fecal-oral | Close contact, contaminated food, "raw oysters" is buzzword

What is the difference in clinical presentation between Hepatitis A and acute Hepatitis B?

Trick question! None

What is unique for Hepatitis A compared to other hepatitis viruses?

No chronic form

What is the therapy for Hepatitis A?

Supportive therapy

What can be done to prevent Hepatitis A infection?

Hep A immunoglobulin | Hep A vaccine

Which hepatitis viruses have an immunoglobulin that can be given for passive immunization?

Hep B and A

Is hepatitis E an RNA or DNA virus?

RNA

What are two major differences between Hepatitis A and Hepatitis E?

Hep E has chronic form that can develop in people who are severely immunosuppressed Hep E has high mortality rate in pregnant women

What is the mode of transmission of Hepatitis E?

Fecal-oral (associated with contaminated water)

Hepatitis Viruses Flashcards

(68 cards)