Hep B Flashcards
Does HBV suppression reduce risk of HCC?
Yes but not enough to stop surveillance. Reduces risk by about 50-60 percent
What are the four phases of HBV infection?
Immune tolerance (whilst a kid- if horizontal transmission skip this often)
Immune clearance
Immune control
Immune escape
Which phases of HBV infection are amenable to treatment?
Immune clearance and immune escape- ALT will be elevated or fluctuating
Hep B - who should you treat?
Immune clearance phase- eAg positive, VL over log 5 or 20 000, abnormal ALT
immune escape- eAg neg, VL over log 3 or 2000 and abnormal ALT
NO POINT in interfering if immune system has it under control
advanced fibrosis - biopsy if fibroscan over 7 kPA
Cirrhotics (but if DNA less than 2000 may treat or observe)
In decompensated cirrhosis and any detectable level DNA- always treat - NOT with IFN!
HCC
Pregnancy
What are the pitfalls of the fibroscan ?
Operator dependent Obesity Narrow rib space Ascites Falsely elevated readings with increased ALT, acute liver injury, liver congestion, cholestasis
Side effects PEG interferon
Flulike
Marrow suppression
Depression and anxiety
Autoimmune disorders especially autoimmune thyroiditis
Does resistance emerge during interferon peg therapy?
No
What factors predict a response to antiviral treatment?
High ALT
low HBV DNA
mild to mod histological activity and stage
More likely to e or s seroconvert if a>b>c>d with peg interferon alpha2B
HBV rna or DNA virus
DNA
What part of the virus is eAg?
Soluble nucleocapsid protein
cvc DNA
covalently closed circular
Becomes established in hepatocyte nuclei so eradication of virus is difficult
Clinical significance of pre-core or core promoter gene mutation
HBeAg neg in chronic HBV
More likely to have progressive liver injury, fluctuating ALT, lower HBV DNA, cannot have tenement induced HBeAg seroconversion.
Benefits of fibroscan
Non invasive
Fast
Well validated in HCV and HBV
Interpretation results fibroscan in HBV
If elevated ALT 1-5 times ULN
Less than 7.5 kPA 96% sensitivity to exclude bridging fibrosis
Over 12- 98% specific for bridging fibrosis
7.5 to 12 consider biopsy
Who should get PEG interferon
Stimulates immune system to clear virus
20-30 percent remission rate
Usually young eAg pos patients to try and prevent long term Tx with nucleoside or nucleotide analogues
Cannot give in cirrhosis
STOP (treatment fertility) if -
eAg positive - if sAg over 20 thousand at week 12
eAg negative- if no drop in sAg and less than 2log
How do you manage lamivudine resistance?
Either-
Add adefovir
Or
Change to tenofovir- current standard
(Likely 20-50% to be resistant to entecavir)
Which nucleos(t)ide analogues are ok in preg?
Lamivudine
Tenofovir
Upside and downside of tenofovir?
Low resistance Hypophosphataemia +/- Fanconi syndrome in 10% -acidosis -low K -glycosuria -rhabdo
Also causes decreased bone density
Maternal factors- highest transmission risk
EAg positive over log 8
Preventing HBV transmission in preg
Passive immunisation at deleted delivery HBIGuf sAg pos
Mode delivery does not matter
HBV immunisation as per national schedule
Antivirus in last trimester if VL over log7- tenofovir cat B. Entecavir not used. Lamivudine cat C.
Cease antiviral a if wish to breast feed
Otherwise continue until week 4 to 12
Post partum flares usually within 4 weeks
Check status child 9 months
Breast feeding does not appear to increase transmission risk - don’t do it if nipples bleeding
Agents that cause HBV reactivation
Steroids EXCEPT asthma or gout Chemo Methotrexate Rituximab Omfatumomab 6MP HIV after immune reconstitution
When is prophylaxis indicated prior to immunosuppressive?
HBsAg or DNA positive: prophylactic analogue to prevent reactivation. Tenofovir good expecially if long term therapy needed. Avoid IFN because bone marrow supression.
HbSAg neg but ant HBc positive, sAb =/- consider if rituximab.
If prophylaxis needs to be given for immunosupression, how do you do it?
Lamivudine if DNA neg and short treatment duration eg standard chemo
entecavir or tenofovir if long duration
HBV DNA less than 2000 then continue 6 months post completion of treatment
Over 2000 continue until end points as if immunocompetent
Strongest predictor of progression to cirrhosis in HBV
HBV DNA load