19 - Blood Borne Viral Diseases Flashcards
Five viruses that cause hepatitis
- HAV
- HBV
- HCV
- HDV
- HEV
HBV, HCV, and HDV transmission
Parenterally
HAV and HEV transmission
Enterally
HBV and HCV
Cause chronic infection, causing cirrhosis and hepatocellular carcinoma
HDV infection
Chronic infection in the presence of HBV
Other viruses that can cause liver inflammation
- CMV
- EBV
- HSV
- Yellow fever
HBV
- 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
HBV surface proteins
HBsAg
HBV structural core protein
HBcAg
Non structural precore proteins
HBeAg
HBV life cycle
- 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
Two types of SVP
- Sphere
- Filament
SVP
- Contain only envelope glycoproteins and host-derived
lipids, and it is not a complete
virion - Non-infectious.
- Involved in antibody neutralisation (decoy)
HBV transmission
- Parenteral (blood transfusion, needlestick injury tattooing)
- Sexual
- Vertical
- Intra-familial
- Aboriginal
How long can HBV survive outside the body and still be capable of causing infection/resistant to common household disinfectants
7 days
Hepatitis B disease
- 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)
Hepatitis symptoms
- Flu like symptoms
- Jaundice
- Itching
Prevention of perinatal HBV transmission
By providing hepatitis B immune globulin and hepatitis B vaccine to their infants within 12 hours of birth
Chance of vertically infected infants will go on to chronicity
90%
HBV infection recovery indications
Clearance of HBsAg from blood and appearance of anti-HBs
HBV chronic infection indications
Persistence of HBsAg >6 months after infection andq lack of anti HBs
HBeAg
Active viral replication
Anti-HBs(Ab) and Anti-Hbe (Ab)
Recovery
Anti-HBc (Ab)
If positive, indicates HBV exposure
Management of chronic hepatitis B
- 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
Example of NUCs
Lamivudine inhibits HBV DNA synthesis ➔ suppression of viral replication and reduction of hepatic necrosis, and HBeAg seroconversion
Hepatitis D virus
- 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
HDV Coinfection
- Both HBV and HDV are acquired simultaneously
- Severe acute disease/ low risk of chronic infection
Superinfection
- Chronic HBV carriers are infected with HDV
- Usually develop chronic HDV infection/ high risk of severe chronic hepatitis
- May present as an acute hepatitis
T/F: Hepatitis D infections can be prevented by hepatitis B immunisation
TRUE
Hepatitis C virus
- 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
HCV structure
- (+)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
HCV genome
- Contains a single, long, open reading frame (3,006-3037 codons) flanked by 5’ and 3’ untranslated regions(UTRs)
- Contains IRES
HCV replication
- Formation of replication complex which replicates the (+)RNA genome through (-) intermediates
- RdRp NS5B is the key enzyme of RNA synthesis.
HCV transmission
- Contact with blood from an infected person and sexual transmission
- 2-6 month incubation period
- 80% asymptomatic
- 70% result in chronic persistent infection
