Hepatitis B Virus - Basics Flashcards
Interpret these HBV serological results
HBsAg -ve
anti-HBc -ve
anti-HBs -ve
1) Never been infected
2) Susceptible to becoming infected
Interpret these HBV serological results
HBsAg -ve
anti-HBc +ve
anti-HBs +ve
1) Previously infected
2) Immune to HBV by serocoversion
Interpret these HBV serological results
HBsAg -ve
anti-HBc -ve
anti-HBs +ve
1) Never been infected
2) Immune to HBV by vaccination
Interpret these HBV serological results HBsAg +ve anti-HBc +ve anti-HBs -ve anti-HBc IgM +ve
1) Acute HBV infection
2) No HBV immunity present
Interpret these HBV serological results HBsAg +ve anti-HBc +ve anti-HBs -ve anti-HBc IgM -ve
1) Chronic HBV infection
2) No HBV immunity present
Interpret these HBV serological results
HBsAg -ve
anti-HBc +ve
anti-HBs -ve
1) Recovering from acute HBV infection
2) Distantly immune and test not sensitive to detect low level of anti-HBs in serum
3) Chronically infected and test not sensitive to detect low level of anti-HBs in serum (occult HBV infection)
4) False+ve HBc in patient without HBV immunity
Define chronic hepatitis B infection
1) Chronic necroinflammatory disease of the liver caused by persistent infection w/HBV –> HBsAg +ve; anti-HBs -ve
2) Subdivide into
1. HBeAg-+ve
2. HBeAg -ve
Define inactive HBsAg carrier state
1) Persistent HBV infection of the live
2) No significant, ongoing necroinflammatory disease.
Define resolved hepatitis B
1) Previous HBV infection
2) No further virological, biochemical, or histological evidence of active virus infection or disease.
Define acute exacerbation/flare of hepatitis B
1) Intermittent elevations of AST/ALT >10x normal
2) Must also be >2x baseline
Define reactivation of hepatitis B
1) Reappearance of active necroinflammatory disease of the liver in 2 kinds of patients
1. Inactive HBsAg carrier state
2. Resolved hepatitis B
Outline the changes in HBsAg from incubation period, acute infection, to chronic infection
1) HBsAg detectable in serum 1-10w after infection
2) anti-HBc IgM detectable in serum during window period when HBsAg disappears but no anti-HBs is present
3) Hepatitis symptoms OR elevated ALT occurs the time AFTER HBsAg and anti-HBc IgM are detected but BEFORE anti-HBs is detected
4) HBsAg undetectable after 4-6m after hepatitis recovery
- persistence >6m = chronic HBV infection
5) Rate of HBsAg clearance in chronic HBV is 0.5% per year
Outline the clinical significance of e-seroconversion
1) Reduction in replication
2) Reduction in infectivity
3) Accompanied by drop in HBV DNA
4) Response to antiviral treatment
Outline the biomarkers used to monitor for active HBV
Reactivation –> indication for HBV antiviral treatment
1) HBV DNA >log 4-5
2) ALT levels >2-3x normal (35 i.e. >70-105
3) Elevations persistent for >3m
HBeAg no longer used for monitoring!!!
1) 10% HBeAg -ve patients still have active disease
2) HBeAg remains +ve in some e-seroconversion patients
Outline the clinical utility of HBeAg
1) Not used for monitoring HBV response/reactivation
2) Can predict sustained viral response
- if HBeAg -ve after antiviral then patient more likely to have sustained response –> try stopping antivirals after 6-12m if HBV DNA and ALT levels normalize
- if HBV DNA and ALT levels remain elevated despite HBeAg -ve then long term antivirals as relapse rate up to 80-90%
Explain why there is a wide difference in HBV carrier rate in various parts of the world. Explain why it is high in Hong Kong
1) Age at infection determines chronicity
2) Infection at a young age = chronic HBV infection
3) Infection at a old age = less chronic HBV infection
4) 70% of HBV cases in Hong Kong are from vertical transmission thus HBV chronicity remains high in HK
5) Theory is that HBV genome becomes integrated into the young patients thus seroconversion is rare
6) Also the rationale why PEG-IFN is only used in HCV but not HBV infections
List the major routes of transmission for HBV
1) Vertical transmission
2) Sexual transmission
3) IV drug users
4) Needle prick injuries
Outline the clinical significance of HBsAg
marker of infection
Outline the clinical significance of HBeAg
marker of replication and infectivity
previously used as monitor for treatment response
no longer reliable; use HBV DNA instead
Outline the clinical significance of HBV DNA
marker of replication and infectivity
more reliable monitor for treatment response
also a marker of HBV reactivation if HBV DNA >log 4-5
Outline the clinical significance of anti-HBeAg
only measured if HBeAg found to be negative
indicates e-seroconversion
patients less infective
Outline the clinical significance of anti-HBcIgM
marker of acute infection
may be the only marker detectable during window period between disappearance of HBsAg and appearance of anti-HBs
unreliable alone as it can persist up to 2y after initial infection
Outline the clinical significance of HBcAg
never checked as HBcAg is an INTRACELLULAR antigen expressed within infected hepatocytes
thus it is normally not detectable in serum
Outline the clinical significance of anti-HBc IgG
marker of past infection
Outline the clinical significance of anti-HBs IgG
marker of HBV immunity
List the types of HBV vaccines
1st generation: purified HbsAg from purified plasma of HBsAg carriers (risk of blood borne infections)
2nd generation: yeast derived recombinant subunit vaccine containing thimerosal (an organic mercurial) as a preservative [neurodevelopmental concerns in children]
3rd generation: mammalian cell derived recombinant subunit vaccine
Which type of HBV vaccine is currently in use in Hong Kong
Yeast derived recombinant subunit vaccines –>2 brands
1) Recombivax HB
2) Engerix-B
State the universal HBV vaccination schedule in Hong Kong
0m
1m
6m
Is pregnancy a contraindication for HBV vaccination?
No
Is breastfeeding contraindicated in HBV carriers?
No but only if the child has received hepatitis B immunogloublin (HBIG)
When should the offspring of hepatitis B positive mothers receive passive and active immunization?
Both should be given at birth preferably within 12h
Passive = HBIG Active = 1st dose HBV yeast derived subunit vaccine
List the phases of chronic HBV infection
1) Replicative phase: immune tolerance
2) Replicative phase: immune clearance
3) Inactive carrier
4) Reactivation (HBeAg -ve chronic hepatitis)
Outline features of replicative phase: immune tolerance in chronic HBV infection
1) Occurs in perinatally acquired HBV infection
- lasts 20-30y
2) High HBeAg = high HBV replication
3) High HBV DNA = high HBV replication
4) Normal ALT = no active liver disease
Outline the clinical significance of replicative phase: immune tolerance in chronic HBV infection
Immune tolerance is thought to be the major reason for poor response to PEG-IFN therapy in HBeAg +ve Asian patients w/normal ALT
But evidence exists that the T cell response in immune tolerance and immune clearance are the same, challenging the immune tolerance concept.
Outline events of replicative phase: immune clearance in chronic HBV infection
1) Occurs in the 20-30s of perinatally acquired HBV
2) High but dropping HBeAg = falling HBV replication
3) High but dropping HBV DNA = falling HBV replication
- during this phase annual spontaneous clearance of HBeAg and HBsAg occurs as follows
- 10-20% (2-15% James) HBeAg
- 1% HBsAg in anti-HBe+ve patients (but retained risk of HCC)
3) Rise in HBV DNA often PRECEDES immune clearance suggesting a rise in viral load triggers immune clearance
4) HBcAg shift from nuclear to cytoplasmic sites within hepatocytes also precedes immune clearance suggesting a change in presentation of viral antigens also triggers immune clearance
5) High ALT = active liver disease
- attributable to sudden increase in immune-mediated lysis of infected hepatocytes
Outline the clinical significance of abortive immune clearance
1) Abortive immune clearance refers to cases in which recurrent exacerbations occur but e-seroconversion or HBV DNA clearance fails
2) Recurrent exacerbations means repeated episodes of hepatitis which increases risk of cirrhosis and HCC
Outline the features of the inactive carrier state in HBV chronic infection
1) HBeAg-ve + anti-HBe+ve
2) Low HBV DNA levels
3) ALT levels variable
- if normal then unlikely to progress to significant liver disease
- if elevated then risk of cirrhosis or HCC; not truly inactive carrier
Outline the diagnosis of inactive carrier state in HBV chronic infection
1) At least 3 HBV DNA less than 4 log
2) At least 3 normal ALT
3) >12m
Outline the features of HBeAg-ve chronic hepatitis
1) HBeAg -ve
2) High HBV DNA
3) High ALT
Outline the features of chronic HBV infection resolution
1) HBsAg -ve
- less than 1% annual clearance in Asians
- up to 2% in Western patients
2) No reduction in risk for cirrhosis or HCC
3) May remain HBV DNA +ve
Outline the diagnosis of HBV chronic infection reactivation
1) HBV DNA >4 log
2) ALT >2-3x
3) >3m
State the lifetime risk for liver related death in Chinese w/chronic HBV
Men –> 40-50%
Women –> 15%
List the risk factors for liver related death in chronic HBV infection
1) Men
2) Repeated abortive immune clearance = delayed e-seroconversion = prolonged replicative phase
3) HBV DNA level >4log (2000IU/mL)
4) HBsAg level >1000IU/mL
What is the annual incidence of relapse in inactive phase for chronic HBV infection?
Which subgroups are at higher risk of reactivation?
2-3%
Which subgroups of HBV chronic infection patients are at higher risk of reactivation?
1) Men
2) e-seroconversion ≥40y/o (i.e. delayed e-seorconversion)
3) HBV genotype C
4) ALT >5x normal during HBeAg+ve phase (replicative phase)
Outline the diagnosis of chronic HBV infection
1) HBsAg +ve >6m
2) HBV DNA > 5log (20000IU/mL)
3) ALT >2-3x normal
