Transcript Slide 1

Hepatitis B- what GI nurses
Need to Know
Mary Pat Pauly MD
Gastroenterology and Hepatology
Kaiser Permanente
Clinical Professor of Internal Medicine and GI
at UC Davis
Hepatitis B
Epidemiology
Modes of transmission
Hepatitis B vaccine
Natural History
Interpretation of serology
Indications for treatment
Newer drugs available for treatment
Importance of ongoing follow up
Hepatitis B
Epidemiology
– Modes of
transmission
Role of Hepatitis B vaccine
Natural History
Interpretation of serology
Indications for treatment
Newer drugs available for
treatment
Importance of
ongoing follow up
Global Impact of Hepatitis B
2 billion with past / present
HBV infection
World Population
6 billion
15–40% develop
cirrhosis, liver failure
or hepatocellular
carcinoma
350–400 million with
chronic hepatitis B
Worldwide: ~1 million / year die from HBV-associated liver disease
United States: Chronically infected ~1.25 million; ~5000 / year die
Korean Mummy Found With
HBV
Virus discovered in the
liver of the South Korean
Handong mummy
– 500-year-old child
– First time HBV ever been
found in a mummified body
Study of the genome of
the 500-year-old virus
under way
– To see if there have been
any significant changes to
HBV over time
Source: Seoul National University
http://www.sciencedaily.com/releases/2007/07/070725093556.htm
Prevalence of HBV in immigrant
populations
Prevalence reflects
pattern of infection
in country of origin
– Africa 10 – 15%
– Asia 10.4%
– Eastern Europe 2-7%
Survey of Asian Am
populations
*Sherman A et al. Hepatology 2005;42:
214A
**Cotler S et al. Clin Gastro & Hep
2009;7:776-80
– 23% in NYC*
– 11.1% in Chicago**
Chronic HBV Prevalence: Asian
Americans in San Francisco (20012006)
80
Prevalence (%)
70
65.4%
60
50
44.8%
40
30
20
10
8.9%
0
Chronic HBV
Positive
Chronic HBV Positive,
Unaware of Serostatus
Lin SY, et al Hepatology. 2007;46:1034-1040.
At Risk: Lack of
Protective Antibodies
Transmission of HBV
HBV
HCV
IVDA
common
common
Transfusion
Before 1980
Before 1992
sexual
common
uncommon
MSM
common
rare
Vertical – mother
to baby
Common
> 90% ->chronic
disease
< 5%
Child  child
Africa 20 – 30% 
chronic disease
Tattoos, piercing
possible
possible
health care worker
possible
possible
28 year old nursing school colleague
– From Taiwan
– In USA since age 10
Applying for job at your hospital
– She was told to get HBV vaccine
– Requirement
Hepatitis B vaccine in employees who are not already
immune to HBV
she was vaccinated when she went to nursing
school
– But HBsAB is neg.
What is your recommendation?
Hepatitis B vaccine
Recommended 3 doses
at 0,1 and 6 months
Protection
– 30 – 50% first dose
– 75% second dose
– 96% with three dose
series
Vaccine is not perfect
– Economic barriers
– Cultural barriers
Some is better than
none….
Protection lower in
Older
HIV
chronic liver diseases
diabetes
obese
smokers
Two vaccines available
– Energix B – 20 mcg
– Recombivax HB – 10 mcg
Acute HBV Infection Incidence*
in the US (1982-2006)
14
Incidence
12
10
8
6
4
2
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
0
Universal
vaccination
of infants
recommended
in 1991
80% decline in
incidence
Year
*Per 100,000 population.
MMWR: Surveillance Summary March 21, 2008 / Vol. 57 / No. SS—2.
Risk factors for HBV in US

5%


16%
42%


18%
CDC Sentinel Counties Study 1991-2006
19%
other*
Non ID
MSM
IDU
Heterosexual
Case continued
Check further into history
– No FH of HBV
21 year old sister in LA who is healthy and without problems
– Family history of mother who died at age 45 from
“cancer in the liver.”
Additional laboratory data
–
–
–
–
HBsAG positive
HBcAB positive
HBsAB negative
ALT 20
What can you tell her about her condition?
Hepatitis B
Epidemiology
Modes of transmission
Hepatitis B vaccine
Natural History
Interpretation of serology
Indications for treatment
Newer drugs available for
treatment
Importance of ongoing
follow up
Spectrum of Disease
Acute HBV infection
90% neonates
~2%
25–30% children
<10% adults
Chronic infection
15–40%
Fulminant hepatic
failure
Progressive chronic
hepatitis
Inactive
carrier state
Cirrhosis
Decompensated
cirrhosis
Death
HCC
EASL Consensus Guidelines. J Hepatol 2003;
Lok, McMahon. Hepatology 2004 (AASLD Guidelines)
Hepatitis B
Epidemiology
Modes of transmission
Hepatitis B vaccine
Natural History
Interpretation of
serology
Indications for treatment
Newer drugs available
for treatment
Importance of ongoing
follow up
Hepatitis B terminology
There are three proteins expressed by the
Hepatitis B virus
Surface antigen
– HBsAg
Core antigen
– HBcAg
Envelope antigen
– HBeAg
Name
Abbreviation Definition
Hepatitis B
Surface Antigen
HBsAg
Protein found on the surface of virus,
indicates active infection.
Hepatitis B
Surface Antibody
HBsAb
Antibody to the surface protein – confers
immunity. Can be result of vaccination or
past infection.
Hepatitis B Core
Antigen
HBcAg
The core protein is inner structure of the
virus and encloses the DNA. Found only in
the liver.
Hepatitis B Core
Antibody
HBcAb
Antibody to the core antigen is found in
chronic hepatitis, resolved acute or chronic
infection. NOT seen in those immune
because of vaccine.
Hepatitis B e
Antigen
HBeAg
This is a soluble protein detected when viral
titers are high. Correlates with infectivity
with the “wild type” HBV.
Hepatitis B e
Antibody
HBeAb
Antibody to the “e” Antigen. Can be seen in
inactive HBV, or chronic active hepatitis
secondary to a mutant: precore or core
promoter mutant.
A few other terms
ALT alanine amino transferase
AST aspartate aminotransferase
– Enzymes liberated by the liver when cells
injured and destroyed
– Tests of liver injury
HBV viral load
– Amount of virus measured in serum
Measured in IU/ml
Natural History of HBV Infection
Early
Childhood
> 95%
Immune
Tolerance
Adulthood
< 5%
HBeAgChronic
Hepatitis B
Cirrhosis
Inactive
Carrier
Courtesy of W. Ray Kim, MD.
Chen DS, et al. J Gastroenterol Hep. 1993;8:470-475.
Seeff L, et al. N Engl J Med. 1987;316:965-970.
HBeAg+
Chronic
Hepatitis B
Natural History of Hepatitis B
Dynamic
– Can go from Active  inactive  active
Liver disease on biopsy
– can progress during periods of activity and
regress during periods of inactivity.
HCC can occur
– in patients with and without cirrhosis
Close clinical follow up is important
Serology of HBV
Infection
ALT HBeAG AntiHBV DNA
HBeAb IU.ml
histology
Immune tolerant
nl
Pos+
Neg-
High
normal
Chronic
hepatitis
HBeAg +
up
Pos+
Neg-
>20,000
active
Inactive carrier
nl
Neg-
Pos+
<2,000
normal
Chronic
hepatitis
HBeAg-
up
Neg-
Pos+
>2,000
active
Our colleague saw a gastroenterologist and had
additional tests ordered.
She presents the following to you for interpretation:
–
–
–
–
–
–
–
HBeAg positive
HBeAb negative
ALT 15, AST 16
Bilirubin, INR and platelet count – normal
HBV DNA –1,000,000 IU/ml 10 (6)
Alpha feto protein –normal
Ultrasound of the liver – normal.
See AASLD guidelines – www.AASLD.org
– This is exactly what is suggested in the AASLD guidelines for the
evaluation of patients with HBV. One would also like to do
complete history. Rule out other causes of liver disease such as
AIH, HCV and HIV. And hemochromatosis.
Adapted from Lok AS, et al. Hepatology. 2007;45:507-539
The next question she asks
Is she a candidate for treatment?
Hepatitis B
Epidemiology
Modes of transmission
Role of Hepatitis B vaccine
Natural History
Interpretation of serology
Indications for
treatment
Newer drugs available for
treatment
Importance of ongoing
follow up
Treatment of HBV
Current Recommendations
Monitor patients in
– Immune tolerant phase
– Inactive –carrier state
Consider treatment
– Chronic Active hepatitis
Wild type – HBeAg positive
Mutant type – HBeAg negative and HBeAb positive
Treat
– Cirrhosis with active viral replication
Consider:
– Age, severity of liver disease, likelihood of response,
potential adverse events
ccc DNA….nasty little viral form
Does not replicate
Impervious to nucleoside/tide
analogue-based therapy
Sits in cell for life of cell
– up to 10 years in immune
tolerant or inactive state
Clearance based on
immune driven hepatocyte
clearance
or cell death
Goals of treatment
Suppression of HBV DNA
– Goal is undetectable
Normal ALT
– No inflammation or ongoing liver injury
Convert from active phase to inactive
– HBeAG positive  negative and HBeAb pos.
Holy Grail
– HBsAg negative, HBsAb positive.
Hepatitis B – what every GI nurse
should know
Epidemiology
Modes of transmission
Role of Hepatitis B vaccine
Natural History
Interpretation of serology
Indications for treatment
Newer drugs available for treatment
Importance of ongoing follow up
Treatment of HBV
Interferon alfa-2b
Lamivudine
Adefovir
1990
1998
2002
Entecavir
Pegylated interferon
alfa 2a
2005
2005
Telbivudine
2006
Tenofovir
2008
Treatment available
Interferon alpha
– Useful in select patients
with HBV
Nucleoside and
nucleotide analogs
– Currently the Rx of choice
Genotype A and B
– Side effects significant
– Minimal SE
– No resistant mutants
– Possibility of resistant
mutants
– MOA
– MOA
Anti-viral
Destroys infected
hepatocytes
– Defined treatment
duration
Supresses but does not
eliminate the virus
– Treatment indefinite
Global Distribution of the 8 HBV
Genotypes
A
G
A, B, C,
D, G
A, D, E
H, F
D
B, C
D
F
A, B, C, D
Arauz-Ruiz P, et al. J Gen Virol. 2002;83:2059-2073. Bell SJ, et al. J Clin Virol. 2005;32:122-127.
Chu CJ, et al. Gastroenterology. 2003;125:444-451. Kidd-Ljunggren K, et al. J Gen Virol.
2002;83:1267-1280. Keeffe EB, et al. Clin Gastroenterol Hepatol. 2004;2:87-106.
Impact of HBV Genotype on
Disease Progression
Genotype C
– severe liver disease
– HCC
Genotype B
– Seroconversion from HBeAg ->
anti-HBe at younger age
Genotypes A and B
– Increased response to
Peginterferon alfa-2a
Keeffe EB, et al. Clin Gastroenterol Hepatol. 2006;4:936-962.
HBV Genotyping
Line Probe Assay
marker line
conj. control
amp. control
Genotype A
Genotype B
Genotype C
Genotype D
Genotype E
Genotype F
Genotype G
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Treatment
Drug
Potency
Resistance
FDA approved
Lamivudine
++
20% at 1 yr;
70% at yr 5
Yes
Adefovir
+
3% at 2 yr
28% at 5 yr
Yes
Entecavir
++++
<2% at 4 yr*
Yes
Tenofovir
++++
None yet
yes
Telbivudine
+++
4% at one yr
11-25% at year 2
yes
Emtricitabine
++
Similar to lamivudine
Not yet
Hepatitis B
Epidemiology
Modes of transmission
Role of Hepatitis B vaccine
Natural History
Interpretation of serology
Indications for treatment
Newer drugs
Importance of
ongoing follow up
Importance of follow up
To monitor for progression of disease
– To monitor those in inactive phases and
– To recommend treatment in active phases
Treament
– Monitor for efficacy
– Monitor for resistance
– monitor for toxicity
To screen patients at high risk for HCC
regularly.
Chronic HBV:
recommended followup
Immune – tolerant:
-Inactive
1. Check ALT every 3-6
months.
2. If ALT increases –
check HBV DNA
Work up further
Consider treatment or
biopsy
3. Screen for HCC in high
risk patients
1. Check ALT every 6 – 12
months
2. If ALT increases
Check HBV DNA
work up further
consider biopsy and
treatment
3. Screen for HCC in high
risk patients.
HBsAg
carrier:
Screening for HCC
Ultrasound and AFP
– AFP every 6 months and
– Ultrasound every 6 – 12 months
Screen high risk patients:
– Family history of HCC
– men over 40, women over 50
– patients with chronic hepatitis with high viral
load
– patients with cirrhosis.
“You can stab it with your
steely anti-virals but you just
can’t kill the beast.”
The Eagles
1977 – Hotel
California
Hepatitis B
with your help,
we
can do
better…