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HBV Training Workshop


HBV Training Workshop Alan Franciscus Editor-in-Chief HBV Advocate / HCV Advocate WWW.HBVAdvocate.org * CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 SUPPLEMENT ... – PowerPoint PPT presentation

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Title: HBV Training Workshop

HBV Training Workshop
  • Alan Franciscus
  • Editor-in-Chief
  • HBV Advocate / HCV Advocate

The Liver
  • About 3 lbs (men)
  • size of a football
  • Blood organ
  • Chemical factory gt 500 chemical functions
  • Metabolizes sugar and fat
  • Stores some vitamins and minerals

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

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
HBV is 50 to 100 times more infectious than HIV
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

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 1994-2003 were infected with
    hepatitis B

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

Asian Population in the United States, 2000 12
  • 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
  • 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

HBV Transmission Concentrations of HBV in Body
Blood Semen Urine
Serum Vaginal fluid Feces
Wounds Saliva Sweat
Breast milk
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

Epidemiologic Characteristics of Patients With
Acute Hepatitis B - US, 2007

Cases Reported with Risk Factor Data Cases Reported with Risk Factor Data
Had gt 1 sex partner 38.3
Homosexual activity (male) 10.5
Sexual contact with CHB patient 6.2
Injection-drug use 15
Surgery 11.7
Household contact of CHB patient 2.3
Percutaneous injury (i.e. needlestick) 4.3
Medical employee with blood contact 0.6
Hemodialysis, blood transfusion 0.2, 0.6
Unknown 58
  • 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

Values total gt 100 because multiple risk
factors could be reported for a single case
Daniel D. Acute Viral Hepatitis in US, 2007. MMWR
CDC Recommends Screening Adults at High Risk
for HBV Infection

Populations Populations
Sexual exposure 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
Percutaneous or mucosal exposure to blood 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 blood-contaminated body fluids Persons with end-stage renal disease
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 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.
Screen for HBV US persons not vaccinated as
infants whose parents were born in regions with
HBV prevalence 8 (in red)
Screen for HBV Persons born in regions with HBV
prevalence 2 (in red)
  • gt 2 - Intermediate to high risk
  • (should be screened with or w/o additional risk
  • lt2 - Low (not required to screen without
    additional risk factors)

Centers for Disease Control and Prevention. MMWR.
200655(RR16). Accessed online October 16, 2007.

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

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

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

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

HBV Prevention
  • HBV Vaccination 3 dose series (Twinrix HAV
  • 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)

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
  • 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

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
  • HBV discovered in 1967 by Dr. Blumberg and
  • Dr. Blumberg awarded Nobel Prize in Medicine in

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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) gt 6 months chronic
  • Gray areas????

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

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

Laboratory Tests
  • Liver tests (ALT/AST) Healthy ALT considered to
    be lt19 for women and lt30 for men
  • CBC, platelets, prothrombin time
  • Liver biopsy
  • AFP liver cancer
  • Ultrasound/MRI/CTscan screen for liver cancer

Chronic HBV Symptoms, Progression and Management
HBV is the second most important carcinogen after
  • Acute
  • Chronic
  • Fever
  • Fatigue
  • Loss of appetite
  • Nausea
  • Vomiting
  • Dark urine
  • Clay-colored stools
  • Jaundice
  • And more
  • Children typically exhibit no symptoms
  • Fatigue
  • Fever
  • Abdominal pain
  • Muscle joint pain
  • Nausea
  • And more..
  • Chronic most people have no symptoms

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

Disease Progression
  • 3,000 4,000 deaths a year
  • 15 - 25 develop serious disease progression
    including cirrhosis, liver failure or liver
  • 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


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

Managing HBV - continued
  • Exercise
  • Support
  • Healthy diet
  • www.myplate.gov

Treatment of Chronic HBV
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. 200439857-861. Keeffe EB.
Clin Gastroenterol Hepatol 20064936-962.
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.

2008 US Algorithm Management of Chronic HBV
Infection HBeAg-positive
HBeAg ()
ALT gt ULN HBV DNA gt 20,000 IU/mL
ALT lt ULN HBV DNA lt 20,000 IU/mL
ALT lt ULN HBV DNA gt 20,000 IU/mL
  • Liver biopsy optional
  • Treat
  • Q 3 mo ALT
  • Q 6 mo HBeAg
  • Consider biopsy if
  • persistent or age gt35
  • Treat if histology abnormal
  • Observe
  • Q 3 6 mo ALT
  • Q 6 12 mo HBeAg

Keeffe EB. Et al Clin Gastroenterol Hepatol.
December 2008 http//www.cghjournal.org/inpress
2008 US Algorithm Management of Chronic HBV
Infection HBeAg-negative
HBeAg (-)
ALT gt ULN HBV DNA gt 2,000 IU/mL
ALT lt ULN HBV DNA lt 2,000 IU/mL
ALT lt ULN HBV DNA gt 2,000IU/mL
  • Q 3 mo ALT HBV DNA
  • Consider biopsy if
  • persistent DNA elevation
  • or age gt35
  • Treat if histology abnormal
  • Liver biopsy optional
  • Treat
  • Q 3 mo ALT x 3, then
  • Q 6 12 mo if ALT still lt1 x ULN

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
Detectable HBV DNA
Undetectable HBV DNA
HBV DNA lt2,000 IU/mL
HBV DNA 2,000 IU/mL
Observe or Treat
Wait List for Transplant
Keeffe EB. Clin Gstroenterol Hepatol.
Significant clinical consequences associated
with LAM resistance in this population
Keeffe EB. Et al Clin Gastroenterol Hepatol.
December 2008 http//www.cghjournal.org/inpress
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.

Chronic HBV Medications
  • 100 medications 100 of the time
  • Resistance
  • Ask about adherence
  • Potentially produce a flare-up small
  • Need to take fasting (2 hrs prior to or 2hrs
    after a meal) BARACLUDE/entecavir
  • Monitoring during treatment

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
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.

Patient Assistance Programs
  • Needymeds.org
  • Partnership for Prescription Assistance
  • Gilead
  • Pegasys
  • GSK
  • BMS
  • Idenix/Norvartis

Recommended Websites
  • HBV Advocate www.hbvdvocate.org
  • CDC Viral Hepatitis www.cdc.gov/hepatitis/
  • Hepatitis B Foundation www.hbf.org
  • www.hivandhepatitis.com
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