Lecture 16 Flashcards

1
Q

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

A

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

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2
Q

Acute HBV infection

A

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

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3
Q

Chronic HBV infection

A

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

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4
Q

What does someone with HBV chronic infection have?

A

surface antigen HsAg carrier

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5
Q

How is HBV transmitted?

A

Blood, sexual, mother-child

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6
Q

HBV transmission in high prevalence areas

A

Perinatal

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7
Q

HBV transmission in medium prevalence areas

A

Childhood and percutaneous transmission

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8
Q

HBV transmission in low prevalence areas

A

Adult/ sexual and percutaneous

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9
Q

What are the S proteins of HBV?

A

HBsAg, L, M, S

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10
Q

What are the core proteins of HBV?

A

HBeAg, HBcAg

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11
Q

What is the incubation period of HBV?

A

1-4 months

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12
Q

What is the development of jaundic in HBV related to?

A

Age

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13
Q

What cells do HBV attach to?

A

Hepatocytes

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14
Q

How is HBV internalised into the cell?

A

Endocytosis and enveloped in an endosome

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15
Q

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

A

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.

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16
Q

How are mature virions released from the hepatocyte?

A

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.

17
Q

What are the 5 phases of chronic HBV infection?

A
  1. Immune tolerant 2. Immune clearance 3. Inactive HBV carrier 4. Reactivated HBV 5. Occult HBV
18
Q

Markers for Phase 1 HBV?

A

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

19
Q

Markers for Phase 2 HBV?

A

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

20
Q

Markers for Phase 3 HBV?

A

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

21
Q

Markers for Phase 4 HBV?

A

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

22
Q

Markers for Phase 5 HBV?

A

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

23
Q

How is chronic HBV treated?

A

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

24
Q

How is chronic HBV monitored?

A

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

25
Q

How is an acute HBV infection diagnosed?

A

IgM anti-HBcAg

26
Q

What kind of vaccine is HBV vaccine?

A

Antibodies to Hep B surface antigen only

27
Q

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

A

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

28
Q

What family and genus is HCV part of?

A

Flaviviridae family
Hepacivirus genus

29
Q

How is HCV spread?

A

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

30
Q

What are the structural protein products of HCV?

A

Core, E1, E2

31
Q

What are the acute and clinical manifestations of HCV?

A

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

32
Q

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

A

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

33
Q

How does HCV drug resistance occur?

A

High replication rates and error prone polymerase

34
Q

HCV Sustained virological response (SVR12)

A

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

35
Q

HCV Non-responder (NR)

A

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

36
Q

HCV Rapid virological response (RVR)

A

Undetectable HCV RNA at 4
weeks

37
Q

HCV Early virological response (EVR)

A

Undetectable HCV RNA at
12 weeks

38
Q

Significance of SVR at 12 weeks?

A

risk of HCV recurrence <1% following treatment
Improved survival

39
Q

How is HCV diagnosed and what is measured?

A

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