Hepatitis Viruses

Question 1

Hepatitis A, E:

• Morphology (in common)
• Differences in classification between HAV and HEV
• Transmission
• Locations

Answer 1

• (+) sense ssRNA, naked, acid-stable
• HAV is a Picornavirus, HEV is a Orthohepevirus (but up until recently it was considered a Calcivirus, so some professors may still think it is)
• Shed in feces, contaminates water supply (developing countries)
• HAV is widespread in the developing world, HEV is mostly limited to South / East Asia, but also exists in Africa and Central America.

Question 2

Hepatitis A:

• Pathogenesis
• Disease
• Diagnosis
• Treatment
• Prevention

Answer 2

• Virus enters intestines, spreads via blood to liver and is directly cytopathic for hepatocytes, impairing liver function
• Jaundice, especially in adults. Anicteric hepatitis in children. Typically lasts about a month. No carrier or chronic state. Very rarely becomes fulminant.
• IgM serology, develops late in infection
• Self-limiting, no treatment
• Prevention: inactivated vaccine recommended for travelers to endemic areas

Question 3

Hepatitis E:

-some general concepts about the disease and pathogenesis, it is unlikely that it will be asked in detail

Answer 3

• Disease is indistinguishable from Hepatitis A based on symptoms. It is also self-limiting, there is no treatment.
• Diagnosis made by detecting IgM antibodies
• There is apparently a vaccine that is only available in China, I don’t know if our professors would know about it

Question 4

Hepatitis B:

• Family, Morphology
• Unique aspects of its replication
• Transmission

Answer 4

• Hepadnavirus, circular partially-dsDNA, enveloped.
• Contains DNA-dependent DNA polymerase + reverse transcriptase. Goes from partially-dsDNA -> ssRNA, then uses RT to go to dsDNA. Does not integrate into host genome, so it’s not a retrovirus.
• Parenteral, during delivery, or sex.

Question 5

Hepatitis B:

• Antigens
• Diagnosis

Answer 5

• ”s” surface or Australia antigen, “e” envelope antigen,” and “c” core antigen
  1. “s” shows up first in infection, and is the one used for the vaccine.
  2. “e” shows up next, then “c”
  3. IgM antibodies for “s” and “e” begin to show up, and the circulating levels of “s” and “e” are lost as the Ig-Ab complexes are equal and thus not shown in labs. Only anti-“c” antibodies are visible
  4. Within 6 months the person should seroconvert to IgG antibodies against “e” and more importantly “s” - this means immune system has won. If not, the virus will remain chronic.
• if “e” antigen” is present at any time, the person is contagious

Question 6

Hepatitis B:

-Possible disease patterns

Answer 6

• Acute Hepatitis then recovery
• Fulminant Hepatitis: rapid destruction of the liver
• Chronic Hepatitis: either asymptomatic carrier, chronic persistent hepatitis (low-grade), or chronic active hepatitis (high-grade, risk of cirrhosis)
• Co-infection or super-infection with hepatitis D
• Adults more typically get acute hepatitis with recovery, children more typically have chronic infection leading to cirrhosis

Note that ALT rises greater than AST are typical for viral hepatitis infections

Question 7

Hepatitis B:

• Pathogenesis
• Non-hepatitis symptoms
• Associated diseases

Answer 7

• Liver injury from CD8+ T cells attack of HBV-infected hepatocytes, also antibodies related to serum sickness
• Immune complexes can deposit in other tissues, causing arthritis, skin, and kidney damage. May see prodromal serum sickness + rash + arthalgia. May cause membranous or membranoproliferative glomerulonephritis.
• HBV related to hepatocellular carcinoma, polyarteritis nodosa

Question 8

Hepatitis B:

• Treatment
• Prevention

Answer 8

• Treatment: Typically not treated except for children and people in chronic or fulminant states. May get NRT’s like Lamividine, Interferon alpha, or immunoglobulins
• Prevention: recombinant “s” antigen vaccine

Question 9

Hepatitis D:
-Morphology
-Transmission
-Diagnosis
-Treatment
-Prevention
(disease on another card)

Answer 9

• ssRNA (-) sense, enveloped, circular genome
• Needs HBV “s” antigen to be infectious
• Diagnosis: not easy because antibodies and antigens disappear quickly from serum
• Treatment: none
• Prevention: HBV vaccine

Question 10

Hepatitis D:

-Disease patterns

Answer 10

1. Co-infection: HDV and HBV transmitted together at the same time, typically more mild as “s” antibodies are formed against both
2. Super-infection: HDV infects someone with chronic HBV. Severe, higher incidence of fulminant hepatitis, greater mortality. Remains chronically infected.

Question 11

Hepatitis C:

• Family, morphology
• Transmission
• Pathogenesis

Answer 11

• Flavivirus, (+) ssRNA, enveloped (with antigenic variability, prone to mutations - vaccine difficult; tendency for chronic state)
• Transmission: Almost always parenteral, occasionally from sex. Incubates for 60-120 days.
• Pathogenesis: mostly immunological reaction against the virus

Question 12

Hepatitis C:

• Disease process
• Diagnosis

Answer 12

• Usually shows no symptoms at acute infection, classically takes years to decades to become symptomatic, at which point it causes chronic hepatitis with eventual progression to cirrhosis. Symptoms mostly based on liver damage, may have mixed cryoglobulinemia, porphyria cutanea tarda, membranoproliferative GN. Risk of hepatocellular carcinoma.
• Diagnosis: few diagnosed until they have had the virus for years. Anti-HCV antibodies

Question 13

Hepatitis C:

-Treatment

Answer 13

• Up until recently, a combination of interferon α and ribavirin were used with strong side effects / low success
• In the last few years, expensive protease inhibitors have become available that cure hepatitis C with high success rate. The right drug is based on testing which hepatitis C is present (high variability). Drugs include Sofosbuvir, Daclatasvir, Ledipasvir.

Question 14

Hepatitis G:

• Morphology / family
• Few details, not very important

Answer 14

• Flavivirus: (+) ssRNA, enveloped.
• Transmissible parenterally. Not proven to cause liver disease (it actually has been renamed to GB-virus C because it doesn’t actually cause hepatitis).
• According to wikipedia. there is some research that potentially shows HIV patients have better outcomes when co-infected with GBV-C