Transcript HBV Training Workshop

HBV Training Workshop
Alan Franciscus
Editor-in-Chief
HBV Advocate / HCV Advocate
WWW.HBVAdvocate.org
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www.hepatitistattoos.org
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The Liver
• About 3 lbs (men) –
size of a football
• Blood organ
• Chemical factory > 500 chemical functions
• Metabolizes sugar and fat
• Stores some vitamins and minerals
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The Liver
• Filters and Detoxifies
▫ Breathed in the air, absorbed through the skin &
by mouth
• Makes proteins to help the blood clot
• The liver can regenerate
• Non-complaining organ
WWW.HBVAdvocate.org
Keep the Liver Healthy
• Be careful with alcohol and drugs
▫ Healthy People: No more than 2 alcoholic
drinks a day – men; no more than 1 alcoholic
drink a day for women
 People with HBV – avoid alcohol
• Get vaccinated against HAV & HBV
• Eat a healthy, balanced diet
HBV Transmission & Prevention
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HBV is 50 to 100 times more infectious than HIV
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HBV Worldwide
• 2 billion people worldwide have been infected
with HBV
• An estimated 240 million people
have chronic hepatitis B (CHB)
• 600,000 annual deaths
§
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Immigration From Endemic Areas
Impacts CHB Prevalence In The United States
• Majority of immigrants have never been vaccinated against HBV
• CDC estimates 450,000 immigrants admitted to the USA between 19942003 were infected with hepatitis B
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Estimates - HBV Statistics - U.S.
• 38,000 new or acute infections
• 800,000 to 1.0 million – chronic infections –
~65% unaware
• 2,000-4,000 deaths a year
▫ 70% of deaths are from liver cancer
• ~1 of 8 Vietnamese Americans
• ~1 of 10 Chinese Americans
• ~1 of 12 Korean Americans
WWW.HBVAdvocate.org
Asian Population in the United States, 2000 = ~12 million4,5
• The Asian American community is projected to grow to 33.4 million
people (or 8% of the total US population) by 2050
▫ 68.9% of Asian Americans living in US are foreign-born
▫ Asian Americans are 2.7 times more likely to develop hepatocellular carcinoma
(HCC) and 2.4 times more likely to die from HCC than their white counterparts
Korean
Chinese
2,734,841
1,228,427
Taiwanese
Asian Indian
Hmong
1,899,599
144,795
186,310
Laotian
198,203
Vietnamese
1,223,736
Filipino
2,364,815
Samoan5
133,281
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HBV Transmission:
Concentrations of HBV in Body Fluids
HIGH
MODERATE
LOW/
NOT
DETECTED
Blood
Serum
Wounds
Semen
Vaginal fluid
Saliva
Urine
Feces
Sweat
Tears
Breast milk
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HBV Transmission (more)
• Blood borne – can live outside the body for at
least 7 days
• Highly infectious in semen and vaginal
secretions
• Sharing needles and works to inject drugs
• Needle stick accidents, Healthcare exposure
• Household – sharing personal items
• Horizontal – childhood – biting, scratching
• Vertical – Mother-to-Child transmission at birth
§
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Epidemiologic Characteristics of
Patients With Acute Hepatitis B US, 2007*
• More than 70% of acute infections
reported in 2007 were attributed
to
▫ sexual activity
▫ injection drug use (IDU)
• Sexual activity accounts for most
HBV transmission in the US
Cases Reported with Risk Factor Data
Characteristic
Had > 1 sex partner
Homosexual activity (male)
Sexual contact with CHB patient
Injection-drug use
Surgery
Household contact of CHB patient
Percutaneous injury (i.e. needlestick)
Medical employee with blood contact
Hemodialysis, blood transfusion
Unknown
*Values
Daniel D. Acute Viral Hepatitis in US, 2007. MMWR 2009;58(No.SS-3).
total > 100% because multiple risk
factors could be reported for a single case
%*
38.3
10.5
6.2
15
11.7
2.3
4.3
0.6
0.2, 0.6
58
§
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CDC Recommends Screening
Adults at High Risk for HBV Infection
Populations
Sexual exposure
•
•
•
•
Percutaneous or
mucosal exposure to
blood
•
•
•
•
Increased HBsAg
Prevalence
• Persons born in regions with high or intermediate prevalence of HBV infection
(HBsAg prevalence ≥2%)
• U.S.-born persons not vaccinated as infants whose parents were born In regions
with high prevalence of HBV infection (HBsAg prevalence ≥8%)
Increased Risk of
Medical
Consequences
•
•
•
•
Sex partners of HBsAg-positive persons
Sexually active persons not in a long-term, mutually monogamous relationship
Persons seeking evaluation or treatment for a sexually transmitted disease
Men who have sex with men
Current or recent IDU
Household contacts of HBsAg-positive persons
Residents and staff of facilities for developmentally disabled persons
Healthcare and public safety workers with risk for exposure to blood or bloodcontaminated body fluids
• Persons with end-stage renal disease
HIV+ persons
International travelers to regions endemic with HBV infection (prevalence of ≥2%)
Persons with immunosuppressive therapy
Persons with elevated ALT or AST of unknown etiology
Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20
15
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Screen for HBV: US persons not vaccinated as infants whose
parents were born in regions with HBV prevalence ≥8% (in red)
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Screen for HBV: Persons born in regions with HBV prevalence
≥ 2% (in red)
> 2% - Intermediate to high risk
(should be screened with or w/o additional risk factors)
<2% - Low (not required to screen without additional risk
factors)
Centers for Disease Control and Prevention. MMWR.
2006;55(RR16). Accessed online October 16, 2007.
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HBV Prevention:
CDC Strategy to Eliminate HBV
• Vaccination at birth
• Screening of all pregnant women
• Vaccination of all previously unvaccinated
children and adolescents
• Vaccination of previously unvaccinated adults at
risk for HBV infection
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HBV Prevention:
Recommended for Vaccination
• Sexual exposure:
▫ Sexual contacts of HBV positive persons
▫ People who are sexually active with more than one
sexual partner w/i the last 6 months
▫ People seeking STD services
▫ Men who have sex with men
WWW.HBVAdvocate.org
HBV Prevention:
Recommended for Vaccination
• Blood/mucous exposure:
▫ Current or recent IDU
▫ Household contact
▫ Residents and staff of facilities for developmentally
disabled Americans
▫ Healthcare and public safety workers who may come
into contact with blood/bodily fluids
▫ People with kidney disease – hemodialysis
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HBV Prevention:
Recommended for Vaccination
• Others:
▫ International travelers who travel to countries that
have higher or intermediate levels of HBV
▫ Persons with chronic liver disease
▫ Persons with HIV
▫ All persons seeking protection from HBV infection
WWW.HBVAdvocate.org
HBV Prevention
• HBV Vaccination – 3 dose series (Twinrix HAV &
HBV)
• Not all respond / not all countries have vaccines
• Safer sex
• Standard safety/universal precautions
• Do not share needles or works to inject drugs
▫ Needle Exchange!
• Do not share personal items (razors, toothbrushes)
WWW.HBVAdvocate.org
More Prevention — Mother to Child
• Every pregnant woman should be screened for
HBV
• 1 in 5 not screened
• Ok to breast feed infants born to HBV-infected
mothers
• Up to 90% of infants born to mothers with
chronic HBV will become chronic unless:
▫ Infant is vaccinated and given immune globulin
within 12 hours of birth – reduces chronic rate to
~10%
WWW.HBVAdvocate.org
Pregnancy and Antiviral Therapy
• Treating pregnant women with HBV
medications – no clear recommendations
• Lamivudine, telbivudine –category C
• Tenofovir – category B
• Third trimester
Benefit vs. risk
Another baby born HBV positive
Mother has high viral load
Diagnosing HBV
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•HBV discovered in 1967 by Dr. Blumberg and colleagues
•Dr. Blumberg awarded Nobel Prize in Medicine in 1976
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Keep it Simple!
• HBV Antibodies (proteins made by body)
• HBV Antigens (HBV viral proteins)
• No HBV surface antibody and no surface antigen –
susceptible – vaccinate
• HBV surface antibody – protected
• HBV DNA (viral load) > 6 months – chronic
• Gray areas????
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HBV DNA — Viral Load
• Expressed in ‘International Units’ – IU/mL
▫ Previously reported in copies —
 IU/mL = 5 - 6 copies
▫ Range: 10 to millions or billions
• Used to:
▫ Confirm active infection
▫ Monitoring
▫ Treatment of chronic HBV
WWW.HBVAdvocate.org
HBV Genotype
• 8 different genotypes – A thru H
▫ Not routinely performed
▫ Genotypes A & B – pegylated interferon
▫ Genotype C – increased risk for disease
progression and liver cancer
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Laboratory Tests
• Liver tests (ALT/AST): Healthy ALT considered
to be <19 for women and <30 for men
• CBC, platelets, prothrombin time
• Liver biopsy
• AFP – liver cancer
• Ultrasound/MRI/CTscan – screen for liver
cancer (HCC)
Chronic HBV: Symptoms,
Progression and Management
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HBV is the second most important carcinogen after tobacco
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Symptoms
Acute
▫
▫
▫
▫
▫
▫
▫
▫
Fever
Fatigue
Loss of appetite
Nausea
Vomiting
Dark urine
Clay-colored stools
Jaundice
◦ And more……
• Children typically exhibit no
symptoms
Chronic
•
•
•
•
•
Fatigue
Fever
Abdominal pain
Muscle & joint pain
Nausea
• And more………..
• Chronic – most people have no
symptoms
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Chronic Infection
• ~90% of Infants born to HBV-infected Mothers
▫ Intervention decreases chronic rate to ~10%
▫ 25 to 50% of children aged 1-5 years
• ~5-6% of Adults
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Disease Progression
• 3,000 – 4,000 deaths a year
• ~15 - 25% develop serious disease progression
including cirrhosis, liver failure or liver cancer
▫ Usually after 20 to 30 years
• Risk factors for disease progression
▫ Host – male gender, advanced age, alcohol use &
cigarette smoking
▫ Other factors – persistent high viral load, coinfection
(HIV or HDV), immunosuppression, HBV genotype C,
HBV mutations, severity and frequency of ALT
elevations
▫ Family history of liver cancer increases risk 2-fold
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Managing Chronic HBV
• Liver biopsy
• Regular office visits and tests
▫ Medical provider will set up a regular schedule of visits
and tests
 Common tests: ALT levels, HBV DNA (viral load), HBV
viral markers, HBV genotype
▫ Screen every 6 to 12 months for liver cancer (AFP /
Ultrasound)
• Avoid alcohol, tobacco and anything that can harm
the liver
WWW.HBVAdvocate.org
Managing HBV - continued
• Exercise
• Support
• Healthy diet:
▫ www.myplate.gov
Treatment of Chronic HBV
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Goals of Treatment for Chronic HBV
Overall Goals:
• Prevent complications of chronic HBV:
▫ Cirrhosis, hepatocellular carcinoma (HCC = liver
cancer), death
• Suppression of HBV
Markers of Treatment Response:
• Decrease serum HBV DNA (viral load) to low or
undetectable levels
• Improve liver histology
• Lowering or normalization of ALT levels
Lok ASF. Hepatology. 2004;39:857-861. Keeffe EB. Clin Gastroenterol Hepatol 2006;4:936-962.
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Keep It Simple!
• Treat:
▫ Elevated ALT
▫ Elevated HBV DNA
▫ Treatment, however, is a complicated process
that takes into account many factors – see next
series of slides….
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2008 US Algorithm
Management of Chronic HBV Infection*
HBeAg-positive
HBeAg (+)
ALT < ULN
HBV DNA
< 20,000 IU/mL
Observe
• Q 3 – 6 mo ALT
• Q 6 – 12 mo HBeAg
ALT < ULN
HBV DNA
> 20,000 IU/mL
• Q 3 mo ALT
• Q 6 mo HBeAg
• Consider biopsy if
persistent or age >35
• Treat if histology abnormal
ALT > ULN
HBV DNA
> 20,000 IU/mL
• Liver biopsy optional
• Treat
Keeffe EB. Et al Clin Gastroenterol Hepatol. December 2008 http://www.cghjournal.org/inpress
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2008 US Algorithm
Management of Chronic HBV Infection
HBeAg-negative
HBeAg (-)
ALT < ULN;
HBV DNA
< 2,000 IU/mL
• Q 3 mo ALT x 3, then
• Q 6 – 12 mo if ALT
still <1 x ULN
ALT < ULN;
HBV DNA >
2,000IU/mL
• Q 3 mo ALT & HBV DNA
• Consider biopsy if
persistent DNA elevation
or age >35
• Treat if histology abnormal
ALT > ULN;
HBV DNA
> 2,000 IU/mL
• Liver biopsy optional
• Treat
Keeffe EB. Et al Clin Gastroenterol Hepatol. December 2008 http://www.cghjournal.org/inpress
2008 US Algorithm
Management of Chronic HBV Infection
Patients with Cirrhosis
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Compensated
HBV DNA
<2,000 IU/mL
HBV DNA
≥2,000 IU/mL
Decompensated
Detectable
HBV DNA
Treat
Observe or
Treat
Undetectable
HBV DNA
Observe
Treat
Wait List for Transplant
Keeffe
EB. Clin clinical
Gstroenterol
Hepatol.associated
2006;4:936-962.
*Significant
consequences
with LAM resistance in this population
Keeffe EB. Et al Clin Gastroenterol Hepatol. December 2008 http://www.cghjournal.org/inpress
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Approved HBV Medications
Generic Name
Brand Name
Manufacturer
Date Approved
Interferon alfa-2b
INTRON® A
Merck/Schering
1991
Lamivudine
EPIVIR-HBV®
GlaxoSmithKline
1998
Adefovir dipivoxil
HEPSERA ™
Gilead Sciences
2002
Entecavir
BARACLUDE ™
Bristol-Myers Squibb
2005
Peginterferon alfa-2a
PEGASYS®
Genentech/Roche
2005
Telbivudine
TYZEKA ™
Idenix/Novartis
2006
Tenofovir
VIREAD ™
Gilead Sciences
2008
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HBV Treatment Side Effects
• Direct antivirals:
▫ Minimal side effects – fatigue, stomach, diarrhea,
muscle weakness and pain
▫ Need to monitor renal function for dosing
• Pegylated interferon:
▫ More severe type of side effects – moderate to
severe fatigue, depression, anxiety, gastro, body
aches and pains, insomnia, etc.
WWW.HBVAdvocate.org
Chronic HBV Medications
• 100% medications; 100% of the time
▫ Resistance
▫ Ask about adherence
▫ Potentially produce a flare-up – small % fulminate
• Need to take fasting (2 hrs prior to or 2hrs after
a meal): BARACLUDE/entecavir
• Monitoring during treatment
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Pregnancy Drug Categories
Drug
Category
Indication
Tenofovir (Viread)
B
HBV and HIV
Telbivudine (Tyzeka)
B
HBV
Interferon (Intron A)
C
HCV and HBV
Pegylated interferon alfa-2a
(Pegasys)
C
HCV and HBV
Pegylated interferon alfa-2b
(PegIntron)
C
HCV
Entecavir (Baraclude)
C
HBV
Adefovir (Hepsera)
C
HBV
Lamivudine (Epivir-HB)
C
HBV and HIV
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Complementary and Alternative
Therapies
• Herbs have the potential to cause damage and
interact with other herbs and medications
▫ Inform your medical provider
▫ Use a reputable herbalist
▫ Acupuncture & Acupressure
▫ Traditional Chinese Medicine
 Meditation, qi qong, tai chi, massage, acupuncture,
acupressure, moxibustion.
WWW.HBVAdvocate.org
Patient Assistance Programs
• Needymeds.org
• Partnership for Prescription Assistance
•
•
•
•
•
Gilead
Pegasys
GSK
BMS
Idenix/Norvartis
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Recommended Websites
• HBV Advocate: www.hbvdvocate.org
• CDC – Viral Hepatitis: www.cdc.gov/hepatitis/
• Hepatitis B Foundation: www.hbf.org
• www.hivandhepatitis.com