Things to add to HBV article, hepadnavirus, components:
Virology of B: DNA virus, incorporates into nucleus, cccDNA forms template for - strand of DNA (2 ways to form cccDNA)
Waiting period
Chronic B AASLD guidelines
6/12 waiting period **
Who to test
- Hyperendemic areas
- MSM
- IVDU
- Close contacts of affected
- Pregnancy
- Dialysis patients
- HIV +
Role of liver biopsy
- In ascertaining cirrhosis in patients in whom treatment is being considered (i.e. ALT > 1.5-2x ULN, DNA +, irrespective of eAg status) with interferon and ? of cirrhosis comes up (high AST:ALT, low plt, low plt:AST ratio)
- In patients with fluctuations of ALT on therapy
- In making a determination on whether to treat high risk patients (Asian males, those with family Hx of HCC, very high DNA)
- PAN
- Papular acrodermatitis of childhood
- Neuropathy (mononeuritis multiplex)
- Membranous vs. membranoproliferative GN
- Serum sickness (4/12)
HBV and pregnancy
- Lamivudine Rx in pregnancy (? data) -> begin Tx at end
- Interferon contraindicated in pregnancy
- Vaccinate child, and give HBIG single dose (ref)
HBV and chemotherapy
When to give Lam vs. interferon to prevent activation? Evidence (good evidence for PEG and C)
Interferon contraindications
- Cirrhosis
- BM suppression
- Solid organ transplant other than liver
- Severe hyper or hypothyroidism
- Pregnancy
- Uncontrolled depression
Screening
AFP AND US for high risk:
In general:
- Cirrhotics with B
- Active hepatitis (be it biochemical or histological)
- Carriers: Asian males > 40, Asian females > 50, Africans > 20, FHx HCC, High DNA, pronged activity (from Morris Sherman's AASLD guidelines Hepatology Nov 2005)
Doses and side effects of therapy
- Interferon-2-alfa, 5 MU d or 10 q / MWF, SE: N/V flu-like/malaise itchiness/hair loss depression, suicidality hyper/hypothyroidism cytopenias
- Duration=24/52 (eAg+) 1 yr (eAg-)
- Efficacy (defined by eAg->eAb OR eAg- -> absence of DNA)
- eAg + 33% (durable 80%)
- eAg - 60-70% BUT NOT DURABLE (20%)
- NRTI (cytidine)
- HIV -: 100 q d HIV +: 150 bid (ensure that HAART is given to prevent mutation)
- Rx duration 52 weeks all comers
- Efficacy
- (eAg + 17-32% poorly durable 50% - 80%)
- (eAg - 60-70%, durable <10%)
- SE = rare, well tolerated, N/V, rare pancreatitits, mutants incl. YMDD
- Mention that it can be used in cirrhotics
- resistance 1 yr = 20% / 5 yr = 70% !! vs. adefovir ~ 2% @ 5 yrs.
- treat for 6/12 AFTER seroconversion, no date for eAg -
NRTI (AMP)
Can be added to YMDD Rx 10 daily S/E = nephropathy
- Rx 1 yr
- 24%/51%
- Not durable
- Decompensated cirrhotics - risk of HRS 2o nephrotoxicity!
- rtN236T is Downstream to YMDD motif