Mcaulliffe - Hepatitis

Question 1

What class of virus does Hepatitis C fall under?

Answer 1

Flaviviridae

Question 2

What is the nucleic acid structure of Hep C?

Answer 2

Positive strand RNA genome

Question 3

What proteins does Hep C encode?

Answer 3

Structural proteins:

• core = E1
• envelope = E2

Non-structural proteins:
- various enzymes involved in viral replication

Question 4

Hepatitis C virology

Answer 4

• very high replication rate
• high genetic variability
• lack of proof-reading function of viral RNA polymerase
• 6 Major genotypes (1-6) that are all only 30% sequence similarity
• genotype 1 is most common in the US

Question 5

How is Hep C usually transmitted?

Answer 5

IV DRUG USE, blood transfusion, sex, from infected mother to infant

Question 6

Acute Hepatitis C infection

Answer 6

Often asymptomatic but if illness arises, it is usually in infants or young woman. This is because they are better able to clear the virus so it is only chronic.

Question 7

Chronic Hep C infection

Answer 7

Often asymptomatic but could have fatigue.
Could have an elevated ALT/AST
Signs of liver disease is usually absent
Some progress into advanced liver disease, cirrhosis, and hepatocellular carcinoma (HCC)

Question 8

Screening for Hep C

Answer 8

HCV antibody via ELISA
Rapid test (OraQuick) - point of care

Question 9

What risk factor makes makes people with Hep C likely to progress into cirrhosis?

Answer 9

Level of inflammation

Question 10

What else are Hep C patients at risk for?

Answer 10

Hepatocellular carcinoma (HCC) due to cirrhosis from Hep C

Question 11

Treatment goals for chronic Hep C

Answer 11

Eradicate HCV as reflected in a sustained virologic response (SVR) to therapy
- SVR = absence of HCV RNA by PCR for 6 months following completion of treatment course.

Question 12

Sustained virologic response (SVR)

Answer 12

Absence of HCV RNA for 6 months following treatment via PCR

Question 13

Current treatment of Hep C

Answer 13

Interferon + Ribavarin

Question 14

Who should be screened for Hep B infection?

Answer 14

• individuals born in high areas of high or intermediate prevalence rates (Asia, Africa, Middle East, South America etc.)
• US born individuals not vaccinated whose parents were born in high endemicity regions
• household and sexual contacts of HBsAg carriers
• Drug users
• men who have sex with men
• prisoners
• chronic ALT elevation , or HCV or HIV infection
• patients who will receive immunosuppressive therapy
• all pregnant women

Question 15

Serologic markers for Hep B infection

Answer 15

HBsAg - hepatitis B surface antigen - marker for active infection
Anti-HBs - antibody to surface antigen - best correlate for immunity. Either tells us that patient has properly been vaccinated or was infected and then recovered.
- Anti-HBcore IgM - appears during acute infection and during flares of chronic hepatitis
- Anti-HBcore IgG/total - lifelong marker of Hep B virus infection, no correlate of activity or immunity.

Question 16

What are the stages of chronic Hep B virus?

Answer 16

1) immune tolerance
2) immune clearance
3) non-replicative phase

Question 17

Immune tolerance phase (of chronic Hep B)

Answer 17

• normal ALT
• asymptomatic
• high HBV DNA levels
• HBeAg +
• minimal or no change on liver biopsy
• high rate of maternal-fetal transmission

Question 18

Immune clearance phase

Answer 18

• AST/ALT may be elevated intermittently or constantly
• severe hepatitis may occur leading to more rapid progression to cirrhosis
• males are at a higher risk
• Non-Asians are more likely to convert HBeAg to anti-HBe and less likely to have hepatitis flares

Question 19

Non-replicative phase (of Hep B virus)

Answer 19

HBeAg -
HBsAg +
HBV DNA low or undetectable
ALT normal/mildly elevated
Reduced inflammation score on biopsy

Question 20

Chronic HBV

Answer 20

Basically, the story here is that people who are in the immune tolerant phase were usually infected. Very early in life when their immune systems ere still very immature so they don’t view the Hep B virus as foreign. This is why the viral DNA numbers are very high but the ASL/ALT numbers are normal. Then for some odd reason, at some point later in life the body starts to mount an immune response against the virus and that is when the AST/ALT numbers go up. Then t some point you get into the non-replicative phase in which DNA numbers come down, AST/ALT numbers ae pretty normal, and there is little inflammation in the liver.

Question 21

Treatment goals of Hep B

Answer 21

Sustained virologic response (Low HBV DNA)
Remission of liver disease (ALT levels)
Prevent cirrhosis, hepatic failure, and hepatic cell carcinoma
Prevent transmission to others

Question 22

Recommended Hep B drugs

Answer 22

Tenofovir
Entecavir
- ET

Question 23

What family does Hep A virus belong to?

Answer 23

Picornaviridae

- If you remember, picornaviridae has a mnemonic - PERCH - in which the H stands for Hep A

Question 24

Transmission of Hep A

Answer 24

Fecal-oral
Person to person
Food borne
Vertical (from mom to child)

Question 25

Risk factors for Hep A

Answer 25

Person to person contact
Men who have sex with men
Contaminated food/water
Daycare
Military
IV drug use
Blood transfusion

Question 26

HIV disease

Answer 26

Incubation is 15-50 days
Replication site appears to go only in the liver
Though, there is no major cytopathic effect (the liver cells don’t appear to be destroyed)
Immune-mediated injury

Clinically: there can be jaundice vs. non-jaundice that varies with age.
Illness is non-specific

Question 27

What would you see first, second, and third, in a Hep A infection?

Answer 27

1) Viremia
2) Hep A virus in the feces
3) symptoms

Question 28

How do you diagnose Hep A?

Answer 28

Elevated liver chemistries - ALT/AST and bilirubin
Diagnosis by serology - anti-HAV IgM
There is no chronic form of Hep A infection and a full recovery is infected
Contagious during incubation period and one week after and ice appears

Question 29

Hep A vaccines

Answer 29

HAVRIX
VAQTA
Twinrix

Question 30

When treating someone who has hepatitis B and will be immunocomprimised say due to chemo, what do you do?

Answer 30

Treat prophylactically with antivirals prior to starting treatment and for 6 months following chemo treatment.