Hepatitis Viruses I

Question 1

Hepatitis means…

Answer 1

…inflammation of the liver.

• The causes of hepatitis are varied and include viruses, bacteria, protozoa and toxins.
• Viral hepatitis accounts for significant cases of hepatitis
• Some hepatitis may result in cirrhosis of liver and hepatocellular carcinoma (HCC)

Question 2

Other Viruses that can cause liver inflammation…

Answer 2

• Epstein–Barr virus (Herpesviridae)
• Cytomegalovirus (Herpesviridae)
• Varicella–zoster virus (Herpesviridae)
• Yellow fever virus (Flaviviridae)

Question 3

Hepatitis A Virus

Answer 3

• Hepatitis A Virus genus of the Picornaviridae family
• ( + ) ss RNA icosohedral naked

Question 4

Hepatitis A Structure

Answer 4

• small, icosahedral l (+) single stranded RNA (7.48 kb)
• 4 structural proteins

Question 5

Hepatitis A Replication

Answer 5

• replicates in the cytoplasm
• the mRNA is encoded as a polyprotein that is further cleaved to various mature proteins
• virus assembly in the cytoplasm lvirus release as a result of cell lysis
• difficult to propagate in vitro lseveral HAV strains

Question 6

HAV Clinical Disease

Answer 6

•Worldwide - Higher incidence in lower socioeconomic population

Question 7

HAV Transmission

Answer 7

•fecal–oral transmission, shellfish (oysters, clams), water, contaminated food, vegetables

Question 8

HAV Incubation

Answer 8

• Virus replicates initially in the enteric mucosa (incubation period 15 – 45 days, mean 25)
• Virus can be found in feces 10-14 days before the onset, replication in intestine, followed by a period of viremia with spread to the liver lmost infections are asymptomatic

Question 9

HAV

Answer 9

lacute hepatitis: replicate in small intestine, ldevelopment of viremia, spreads to liver

• replicates in the liver and causes necrosis of liver lonset is sudden after 14–40 days incubation
• The response to replication in the liver consists of lymphoid cell infiltration, necrosis of liver parenchymal cells, and proliferation of Kupffer cells. A variable degree of biliary stasis may be present
• Cytotoxic T lymphocytes (CTLs) damage the hepatocytes
• Initial immune response is the development of HAVspecific IgM antibody followed by appearance of IgG after a few weeks

Question 10

HAV Symptoms

Answer 10

• fever, poor appetite, nausea, headache, malaise, vomiting, abdominal pain, jaundice (may not develop in children), dark urine, clay-colored stool, enlarged liver
• usually self–limiting (complete recovery), immunity is complete
• In rare cases (~0.1%) fulminant hepatitis is associated with extensive liver necrosis

Question 11

HAV Prevention

Answer 11

• Immune serum globulin administered before or during incubation period. (Household members, travelers going to endemic areas)
• Inactivated Hepatitis A Vaccine: Havrix and VAQTA Inactivated Hepatitis A virus strain HM175
• Booster: 6-12 month after the initial dose
• Active immunization is as effective as ISG, if given shortly after exposure.
• 92% decline in HAV since vaccination (1995)

Question 12

Hepatitis B Virus

Answer 12

• Hepatitis B Virus genus of the Hepadnaviridae family
• partially ds DNA icosohedral enveloped

Question 13

Hepatitis B Structure

Answer 13

• Small (42 nm), circular, smallest DNA virus
• Partially double stranded DNA 3200 nucleotides associated with viral DNA polymerase
• HBcAg (core antigen) encloses DNA
• HBeAg (encoded by core gene), glycoprotein
• HBsAg (surface antigen) surrounds the core, envelope
• 4 subtypes of HBsAg (adw, ayw, adr, ayr)

Question 14

HBV Replication

Answer 14

• Full length (+)RNA is inserted into core
• Reverse transcriptase synthesizes a full length (–)DNA strand using the (+)RNA template
• (–)DNA template is used to make a variable short piece of (+)DNA l RNA degrades in the core
• Virus assembly in the cytoplasm
• Acquires envelope from Golgi or ER membranes
• Released from the cells

Question 15

HBV Epidemiology

Answer 15

• Worldwide, in the United States 0.1 to 0.5% of the population are chronic carriers
• 50% infections in U.S. are sexually transmitted

Question 16

HBV Pathogenesis

Answer 16

• Immunologic responses
• Serum-sickness like rash and arthritis, jaundice
• Circulating immune complexes activate complement system
• CTL kills infected cells causing damage to liver, type IV hypersensitivity
• Insufficient T-cell function increase the risk of chronicity

Question 17

HBV Clinical Disease

Answer 17

• acute hepatitis B (similar to Hepatitis A) but differs in longer incubation period (mean 60-90 days)
• onset tends to be slow
• mode of transmission is usually through body fluid (blood, saliva, semen, cervical secretions, blood products)
• vertical transmission to infants tends to be more severe
• chronic carriers arise in about 10% of infections

Question 18

Chronic HBV

Answer 18

• 10-20% adult cases become chronic
• ~90% chronicity in newborns after transmission
• main reservoirs of infection - liver
• Virus replicates in the liver
• Integrated HBV DNA may be present
• Covalently closed circular DNA (cccDNA) in the nucleus forms the mini-chromosome and provides stability to HBV DNA for persistence
• demonstrate HBsAg in serum (for life)
• Anti-HBc and HBeAg are also seen in chronicity
• Cirrhosis of liver
• Hepatocellular carcinoma (HCC) (200–fold increased risk)
• HBV DNA found in nearly all HCC cases
• Mechanisms of role of HBV in HCC is unclear

Question 19

HBV Diagnosis Acute Hepatitis B

Answer 19

Question 20

HBV Diagnosis Chronic Hepatitis B

Answer 20

Question 21

HBV Treatment

Answer 21

•Interferon-alpha, Lamivudine (3TC), nucleoside and nucleotide analogs are active

Question 22

HBV Prevention

Answer 22

• hyperimmune globulin (passive)
• HBV Vaccine: HBsAg from carriers (fixed) ,HBsAg synthesized in yeasts, humoral immunity