19 - Blood Borne Viral Diseases

Question 1

Five viruses that cause hepatitis

Answer 1

• HAV
• HBV
• HCV
• HDV
• HEV

Question 2

HBV, HCV, and HDV transmission

Answer 2

Parenterally

Question 3

HAV and HEV transmission

Answer 3

Enterally

Question 4

HBV and HCV

Answer 4

Cause chronic infection, causing cirrhosis and hepatocellular carcinoma

Question 5

HDV infection

Answer 5

Chronic infection in the presence of HBV

Question 6

Other viruses that can cause liver inflammation

Answer 6

• CMV
• EBV
• HSV
• Yellow fever

Question 7

HBV

Answer 7

• Partially ds circular DNA 3.2kb
• 4 overlapping open reading frames (S, C, P and X) that encode surface proteins, structural core protein, polymerase, and non structural precore proteins

Question 8

HBV surface proteins

Answer 8

HBsAg

Question 9

HBV structural core protein

Answer 9

HBcAg

Question 10

Non structural precore proteins

Answer 10

HBeAg

Question 11

HBV life cycle

Answer 11

• Relaxed circular DNA (RC-DNA) –> cccDNA
• DNA is transcribed by host RNA polymerase into pregenomic RNA (pgRNA) and subgenomic mRNAs
• pgRNA is encapsidated, together with the P protein, and reverse transcribed inside the nucleocapsid
• (+)DNA synthesis from the (-)DNA template generates new RC-DNA
• Subviral particles (SVP) are present at much higher concentration than viral particles (VP) in serum

Question 12

Two types of SVP

Answer 12

• Sphere
• Filament

Question 13

SVP

Answer 13

• Contain only envelope glycoproteins and host-derived
  lipids, and it is not a complete
  virion
• Non-infectious.
• Involved in antibody neutralisation (decoy)

Question 14

HBV transmission

Answer 14

• Parenteral (blood transfusion, needlestick injury tattooing)
• Sexual
• Vertical
• Intra-familial
• Aboriginal

Question 15

How long can HBV survive outside the body and still be capable of causing infection/resistant to common household disinfectants

Answer 15

7 days

Question 16

Hepatitis B disease

Answer 16

• 45-180 day incubation period
• Can cause acute and chronic disease
• Most acute infections are symptomatic and cleared by IR
• ~10% of infections are not cleared and virus continues to replicate
• Risk of chronic infection varies according to age at infection (greatest in young children)

Question 17

Hepatitis symptoms

Answer 17

• Flu like symptoms
• Jaundice
• Itching

Question 18

Prevention of perinatal HBV transmission

Answer 18

By providing hepatitis B immune globulin and hepatitis B vaccine to their infants within 12 hours of birth

Question 19

Chance of vertically infected infants will go on to chronicity

Answer 19

90%

Question 20

HBV infection recovery indications

Answer 20

Clearance of HBsAg from blood and appearance of anti-HBs

Question 21

HBV chronic infection indications

Answer 21

Persistence of HBsAg >6 months after infection andq lack of anti HBs

Question 22

HBeAg

Answer 22

Active viral replication

Question 23

Anti-HBs(Ab) and Anti-Hbe (Ab)

Answer 23

Recovery

Question 24

Anti-HBc (Ab)

Answer 24

If positive, indicates HBV exposure

Question 25

Management of chronic hepatitis B

Answer 25

- Based on levels of serum HBV DNA, ALT and severity of liver disease - Nucleoside or nucleotide analogues (NUCs) - however Antiretroviral treatment can select for drug resistant virus

Question 26

Example of NUCs

Answer 26

Lamivudine inhibits HBV DNA synthesis ➔ suppression of viral replication and reduction of hepatic necrosis, and HBeAg seroconversion

Question 27

Hepatitis D virus

Answer 27

- Circular,ssRNA(-) genome of 1,68 kb - Unique virus dependent on HBV - enveloped (HBsAg) - Considered a satellite virus of HBV but does not share sequence similarity (can replicate independently of HBV.) - Range of clinical outcomes from asymptomatic infection to fulminant hepatitis

Question 28

HDV Coinfection

Answer 28

- Both HBV and HDV are acquired simultaneously - Severe acute disease/ low risk of chronic infection

Question 29

Superinfection

Answer 29

- Chronic HBV carriers are infected with HDV - Usually develop chronic HDV infection/ high risk of severe chronic hepatitis - May present as an acute hepatitis

Question 30

T/F: Hepatitis D infections can be prevented by hepatitis B immunisation

Answer 30

TRUE

Question 31

Hepatitis C virus

Answer 31

- High propensity for establishing chronic infection - Can lead to advanced liver fibrosis, cirrhosis and hepatocellular carcinoma - Most common indication for liver transplantation in developed countries. - Unlike HBV, is curable

Question 32

HCV structure

Answer 32

- (+)ssRNA approximately 9,600 nucleotide bases in length. - Flaviviridae family - Circulate as a hybrid lipoviral particle that consists of lipoproteins tightly associated with the HCV particle. - The formation of the lipoviral particle facilitates HCV entry into hepatocytes and it protects HCV from antibody neutralisation - 8 recognised genotypes

Question 33

HCV genome

Answer 33

- Contains a single, long, open reading frame (3,006-3037 codons) flanked by 5' and 3' untranslated regions(UTRs) - Contains IRES

Question 34

HCV replication

Answer 34

- Formation of replication complex which replicates the (+)RNA genome through (-) intermediates - RdRp NS5B is the key enzyme of RNA synthesis.

Question 35

HCV transmission

Answer 35

- Contact with blood from an infected person and sexual transmission - 2-6 month incubation period - 80% asymptomatic - 70% result in chronic persistent infection