Lecture 16

Question 1

What does HBV cause and what are the two types of infection

Answer 1

Chronic hepatitis, cirrhosis, hepatocellular carcinoma (HCC). Chronic and acute

Question 2

Acute HBV infection

Answer 2

(< 6 months) – asymptomatic or icteric hepatitis
or fulminant

Question 3

Chronic HBV infection

Answer 3

(> 6 months) - healthy carrier or cirrhosis and
HCC

Question 4

What does someone with HBV chronic infection have?

Answer 4

surface antigen HsAg carrier

Question 5

How is HBV transmitted?

Answer 5

Blood, sexual, mother-child

Question 6

HBV transmission in high prevalence areas

Answer 6

Perinatal

Question 7

HBV transmission in medium prevalence areas

Answer 7

Childhood and percutaneous transmission

Question 8

HBV transmission in low prevalence areas

Answer 8

Adult/ sexual and percutaneous

Question 9

What are the S proteins of HBV?

Answer 9

HBsAg, L, M, S

Question 10

What are the core proteins of HBV?

Answer 10

HBeAg, HBcAg

Question 11

What is the incubation period of HBV?

Answer 11

1-4 months

Question 12

What is the development of jaundic in HBV related to?

Answer 12

Age

Question 13

What cells do HBV attach to?

Answer 13

Hepatocytes

Question 14

How is HBV internalised into the cell?

Answer 14

Endocytosis and enveloped in an endosome

Question 15

What happens after the viral genome is released in the cytoplasm?

Answer 15

Once the viral genome is released into the cytoplasm, it is transported to the nucleus of the hepatocyte, where it is converted into covalently closed circular DNA (cccDNA). The cccDNA serves as a template for the transcription of viral RNA and the synthesis of viral proteins.

Question 16

How are mature virions released from the hepatocyte?

Answer 16

the mature virions are released from the hepatocyte by budding from the endoplasmic reticulum and Golgi apparatus, and are then released into the bloodstream, where they can infect other hepatocytes and continue the lifecycle of the virus.

Question 17

What are the 5 phases of chronic HBV infection?

Answer 17

1. Immune tolerant 2. Immune clearance 3. Inactive HBV carrier 4. Reactivated HBV 5. Occult HBV

Question 18

Markers for Phase 1 HBV?

Answer 18

HepB e-antigen and antibody
HepB s-antigen and antibody
High HBV DNA

Question 19

Markers for Phase 2 HBV?

Answer 19

HepB e antigen and antibody
HepB s-antigen and antibody
High HBV DNA fluctuating

Question 20

Markers for Phase 3 HBV?

Answer 20

HBsAg positive, HBe negative; Anti-HBe positive, low HBV DNA
Loq risk of cirrhosis

Question 21

Markers for Phase 4 HBV?

Answer 21

Asymptomatic or symptoms
HBsAg positive, Anti-HBe positive, HBe negative, high HBV DNA and fluctuating ALT levels

Question 22

Markers for Phase 5 HBV?

Answer 22

Unexplained liver disease in HBsAg negative, plus/minus anti-HBs individuals
Detectable HBV DNA in blood or liver by sensitive molecular methods
Mutations in HBs promoter

Question 23

How is chronic HBV treated?

Answer 23

Pegylated Interferon (PEG-IFN
Nucleoside analogs: TV, TDF and TAF

Question 24

How is chronic HBV monitored?

Answer 24

Molecular assays for HBV viral load
Biochemical assay for liver enzymes/ histology
Serology for HBeAg and anti- HBeAg

Question 25

How is an acute HBV infection diagnosed?

Answer 25

IgM anti-HBcAg

Question 26

What kind of vaccine is HBV vaccine?

Answer 26

Antibodies to Hep B surface antigen only

Question 27

What vaccine is given to children of HBV-positive mothers?

Answer 27

HBIG plus vaccine should be given to infants born to HBV positive mothers and after accidental high risk exposure

Question 28

What family and genus is HCV part of?

Answer 28

Flaviviridae family Hepacivirus genus

Question 29

How is HCV spread?

Answer 29

Blood, person-person (healthcare workers), sexual, vertical

Question 30

What are the structural protein products of HCV?

Answer 30

Core, E1, E2

Question 31

What are the acute and clinical manifestations of HCV?

Answer 31

Acute HCV: malaise, nausea, dark urine, Jaundice; incubation period 7 weeks; HCV RNA detected in blood within days of exposure followed by elevations in ALT and AST levels Chronic HCV: 50-80% of acute infections become chronic - Few symptoms lasts decades - ALT levels may fluctuate, HCV RNA constant, - Liver inflammation varies over time - 20% develop cirrhosis of which 25% develop HCC

Question 32

What are the direct acting antiviral used in interferon free treatment of HCV and what do they target?

Answer 32

Voxilaprevir targets the N53 and NS4A of serine protease Velpatasvir targets NS5A of viral replication system Sofosbuvir targets NS5B

Question 33

How does HCV drug resistance occur?

Answer 33

High replication rates and error prone polymerase

Question 34

HCV Sustained virological response (SVR12)

Answer 34

refers to the absence of HCV RNA in serum 12 weeks after stopping treatment

Question 35

HCV Non-responder (NR)

Answer 35

refers to persons in whom HCV RNA levels remain stable during treatment

Question 36

HCV Rapid virological response (RVR)

Answer 36

Undetectable HCV RNA at 4 weeks

Question 37

HCV Early virological response (EVR)

Answer 37

Undetectable HCV RNA at 12 weeks

Question 38

Significance of SVR at 12 weeks?

Answer 38

risk of HCV recurrence <1% following treatment Improved survival

Question 39

How is HCV diagnosed and what is measured?

Answer 39

ELISA measures antibodies against NS4, Core, NS3, NS5 6-8 weeks after exposure; “antigen-antibody combo” ELISAs