Hepatitis A,B and C

Question 1

1. Are the 6 hepatitis viruses related?
2. What cells do all the viruses infect?
3. Is there a vaccine to Hep C?

Answer 1

1. No
2. Hepatocytes, cause liver pathology
3. No, only A,B,E

Question 2

1. What type of virus is Hepatitis A?
2. What aspect of Hep A makes it a good candidate for vaccines?
3. If the virus isn’t very hepatotoxic, what makes it have such a huge effect on the body?

Answer 2

1. Enterovirus, human-restricted picornavirus with fecal-oral transmission, highly environmentally stable
2. Only one serotype exists
3. Symptoms are largely immunogenic - >90% of patients recover completely with no chronic infection, rarely patients develop fulminant hepatitis with 40% mortality

Question 3

How do you diagnose Hep A?

Answer 3

Enzyme Immunoassay (EIA) for Anti-HepA IgM indicates acute infection, EgG indicates past infection, vaccination, High ALT levels indicate ongoing liver damage

Question 4

How do you treat and prevent Hep A?

Answer 4

Treatment is symptomatic, bed rest, hydration, careful with Tylenol. Prevention is with handwashing, sanitation, water treatment and HepA vaccine, prophylaxis with immune serum globulin

Question 5

1. What is the morphology and genome type of Hepatitis B?
2. What is one type of immune evasion that this virus performs?
3. Is there a vaccine?
4. What is the life cycle?

Answer 5

1. Small, enveloped, DNA virus (but carries a reverse transcriptase and replicates through RNA intermediate), partly double stranded - it is unusually stable for an enveloped virus
2. There are 1000X more HBsAg decoys than virions
3. Since there is only one serotype there is an effective vaccine available
4. Replicates in hepatocytes and leaves behind integrated copies of viral DNA

Question 6

How is hepatitis B transmitted?

Answer 6

Efficiently by injection of contaminated blood, less efficiently by sexual or birth contact

Question 7

What are the four stages of HepB / Immune interaction?

Answer 7

1- immune tolerance, virus replicates without symptoms. hepB DNA and antigens in serum, but little antibody
2- Immunogenic symptoms. ALT increases, HepB DNA declines, can have an acute symptomatic per. or lasts for years
3- Clearing the virus, viral replication shuts down, HBeAb detected, HepB DNA not detected, ALT declines, HBsAg remains
4- Virus cleared, no viral antigens, permaent IgG

Question 8

What are the HBV Infection outcomes in adults?

Answer 8

most people have a 90% resolution, others have HBsAg + detection for >6 months. Of these cases, 50% have resolution, others have carrier state, chronic persistent (deposits of immune complexes) or chronic active hepatitis (cirrhosis, carcinoma)

Question 9

What are three facets of HepB chronic infection?

Answer 9

1- Ongoing cytotoxic T-cell response against infected hepatocytes causes permanent cirrhosis - the virus itself is NOT hepatotoxic
2- Accumulation of Hep antigen-antibody complexes leads to kidney damage and arthritis
3- Virus genome integration, expression of viral transcriptional transactivators, and chronic inflammation lead to cancer

Question 10

Hepatitis B Prevention

Answer 10

Vaccination, raises neutralizing antibody, blocks virus entry
second-best option is antibody prophylaxis. Immune globulin is administered shortly prior to exposure
Combo of both given for needle sticks and newborns with HBV+ mothers

Question 11

Hepatitis B Treatment

Answer 11

Provide supportive care for acute hepatitis, drug treatment for chronic active infection but cure rate low - 1 yr of polymerase inhibitors and 4 months of pegylated alpha-interferon (significantly toxic with heavy side effects)

Transplant may be indicated for late stage if treatment fails: watch liver function markers and mental status - need patient education! many ppl don’t know Hep B is sexually transmitted

Question 12

What do interferon molecules do?

Answer 12

interferons stimulate cells to turn on genes for antiviral proteins, inert cells around the initial cell

Question 13

1. What is the morphology and genome type of Hepatitis C?
2. How is Hep C transmitted?
3. What is the difference in prognosis between Hep B and C?
4. Vaccine?

Answer 13

1. human-restricted flavivirus, enveloped + RNA genome
2. By blood, inefficiently by sex
3. Much higher potential for chronic infection than Hep B, stronger association with primary hepatocellular carcinoma
4. No!

Question 14

1. What does HCV infect?

2. Does it generate a quasispecies?

Answer 14

1. Hepatocytes and possible B lymphocytes (both carry CD 81 receptor) - B lymphocytes might be the other reservoir! - Less than half of people infected clear it, it requires a strong cytotoxic T response - 85% people infected with hep C have persistent infection-> chronic
2. Yes! Highly mutagenic (rdRNAP has no proofreading)

Question 15

How are you able to diagnosis HepC?

Answer 15

Acute symptoms similar to HBV, somewhat milder, travel to Egypt, many old cases are still being uncovered

Question 16

How do you diagnose HepC?

Answer 16

Serology: Liver function tests include ALT levels, autoantibodies, cryoglobulin
ELISA followed by RIBA (western blot), if positive, HCV genotyping
RT-PCR for viral RNA levels to assess success of therapy

Question 17

Hepatitis C treatment during an acute infection

Answer 17

Antibody to HCV is not protective - during an acute infection, a judgement call is required - short course of peg-alpha-IFN treatment reduces rates of chronic infection, but infection may spontaneously clear without treatment

Question 18

Hep C treatment during chronic infection with ongoing damage

Answer 18

Ribavirin: antiviral and immunomodulatory (can cause birth defects)

pegylated-alpha-interferon: antiviral (will cause many side effects)

if serotype 1 - HCV protease inhibitors: Increases sustained viral response (SVR) rates by 20-40%, but has additional side effects

The goal of treatment is sustained viral response - like remission. “failed” treatment may still reduce risk of hepatocellular carcinoma

Question 19

Living-Donor Liver Transplant (LDLT) for Hep C

Answer 19

If a type-matched living donor is available:

1) Start hard course of antivirals to clear extrahepatic virus reservoirs before transplant
2) Remove diseased liver and most of virus
3) Replace with partial donor liver