Lecture 16 Flashcards
What does HBV cause and what are the two types of infection
Chronic hepatitis, cirrhosis, hepatocellular carcinoma (HCC). Chronic and acute
Acute HBV infection
(< 6 months) – asymptomatic or icteric hepatitis
or fulminant
Chronic HBV infection
(> 6 months) - healthy carrier or cirrhosis and
HCC
What does someone with HBV chronic infection have?
surface antigen HsAg carrier
How is HBV transmitted?
Blood, sexual, mother-child
HBV transmission in high prevalence areas
Perinatal
HBV transmission in medium prevalence areas
Childhood and percutaneous transmission
HBV transmission in low prevalence areas
Adult/ sexual and percutaneous
What are the S proteins of HBV?
HBsAg, L, M, S
What are the core proteins of HBV?
HBeAg, HBcAg
What is the incubation period of HBV?
1-4 months
What is the development of jaundic in HBV related to?
Age
What cells do HBV attach to?
Hepatocytes
How is HBV internalised into the cell?
Endocytosis and enveloped in an endosome
What happens after the viral genome is released in the cytoplasm?
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.
How are mature virions released from the hepatocyte?
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.
What are the 5 phases of chronic HBV infection?
- Immune tolerant 2. Immune clearance 3. Inactive HBV carrier 4. Reactivated HBV 5. Occult HBV
Markers for Phase 1 HBV?
HepB e-antigen and antibody
HepB s-antigen and antibody
High HBV DNA
Markers for Phase 2 HBV?
HepB e antigen and antibody
HepB s-antigen and antibody
High HBV DNA fluctuating
Markers for Phase 3 HBV?
HBsAg positive, HBe negative; Anti-HBe positive, low HBV DNA
Loq risk of cirrhosis
Markers for Phase 4 HBV?
Asymptomatic or symptoms
HBsAg positive, Anti-HBe positive, HBe negative, high HBV DNA and fluctuating ALT levels
Markers for Phase 5 HBV?
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
How is chronic HBV treated?
Pegylated Interferon (PEG-IFN
Nucleoside analogs: TV, TDF and TAF
How is chronic HBV monitored?
Molecular assays for HBV viral load
Biochemical assay for liver enzymes/ histology
Serology for HBeAg and anti- HBeAg
How is an acute HBV infection diagnosed?
IgM anti-HBcAg
What kind of vaccine is HBV vaccine?
Antibodies to Hep B surface antigen only
What vaccine is given to children of HBV-positive mothers?
HBIG plus vaccine should be given to infants born to HBV positive
mothers and after accidental high risk exposure
What family and genus is HCV part of?
Flaviviridae family
Hepacivirus genus
How is HCV spread?
Blood, person-person (healthcare workers), sexual, vertical
What are the structural protein products of HCV?
Core, E1, E2
What are the acute and clinical manifestations of HCV?
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
What are the direct acting antiviral used in interferon free treatment of HCV and what do they target?
Voxilaprevir targets the N53 and NS4A of serine protease
Velpatasvir targets NS5A of viral replication system
Sofosbuvir targets NS5B
How does HCV drug resistance occur?
High replication rates and error prone polymerase
HCV Sustained virological response (SVR12)
refers to the absence of
HCV RNA in serum 12 weeks after stopping treatment
HCV Non-responder (NR)
refers to persons in whom HCV RNA levels
remain stable during treatment
HCV Rapid virological response (RVR)
Undetectable HCV RNA at 4
weeks
HCV Early virological response (EVR)
Undetectable HCV RNA at
12 weeks
Significance of SVR at 12 weeks?
risk of HCV recurrence <1% following treatment
Improved survival
How is HCV diagnosed and what is measured?
ELISA measures antibodies against NS4, Core, NS3, NS5
6-8 weeks after exposure; “antigen-antibody combo” ELISAs
