Transcript HBV Training Workshop
HBV Training Workshop
Alan Franciscus Editor-in-Chief HBV Advocate / HCV Advocate
WWW.HBVAdvocate.org
www.HBVAdvocate.org
WWW.HBVAdvocate.org
WWW.HBVAdvocate.org
www.hcvadvocate.org
www.hepatitistattoos.org
WWW.HBVAdvocate.org
WWW.HBVAdvocate.org
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
WWW.HBVAdvocate.org
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
WWW.HBVAdvocate.org HBV is 50 to 100 times more infectious than HIV
WWW.HBVAdvocate.org
HBV Worldwide
• 2 billion people worldwide are infected with HBV ▫ An estimated 400-800 million people have chronic hepatitis B (CHB) 2,3 • Complications from HBV are the 10 th cause of death worldwide leading
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
§
WWW.HBVAdvocate.org
Estimates - HBV Statistics - U.S.
• 43,000 new or acute infections • 2-3 million – chronic infections - ~65% unaware • 3,000-4,000 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 million 4,5
• 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
Asian Indian 1,899,599 Chinese 2,734,841 Korean 1,228,427 Laotian 198,203 Hmong 186,310 Vietnamese 1,223,736 Taiwanese 144,795 Filipino 2,364,815 Samoan 5 133,281
HIGH
WWW.HBVAdvocate.org
HBV Transmission:
Concentrations of HBV in Body Fluids
Blood Serum Wounds
MODERATE LOW/ NOT DETECTED
Semen Urine Vaginal fluid Feces Saliva Sweat Tears Breast milk
WWW.HBVAdvocate.org
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
* • • 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 Daniel D. Acute Viral Hepatitis in US, 2007. MMWR 2009;58(No.SS-3).
Cases Reported with Risk Factor Data Characteristic Had > 1 sex partner Homosexual activity (male) Sexual contact with CHB patient Injection-drug use Household contact of CHB patient Percutaneous injury (i.e. needlestick) Medical employee with blood contact Hemodialysis, blood transfusion Unknown
* Values 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 §
§
CDC Recommends Screening Adults at High Risk for HBV Infection
Sexual exposure Percutaneous or mucosal exposure to blood Increased HBsAg Prevalence Increased Risk of Medical Consequences Populations
• • • •
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 blood contaminated body fluids Persons with end-stage renal disease
• •
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%)
• • • •
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
16
WWW.HBVAdvocate.org
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) Centers for Disease Control and Prevention.
MMWR.
2006;55(RR16). Accessed online October 16, 2007.
> 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)
WWW.HBVAdvocate.org
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
WWW.HBVAdvocate.org
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
WWW.HBVAdvocate.org
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% • Treating pregnant women with HBV medications – no clear recommendations
Diagnosing HBV
WWW.HBVAdvocate.org •HBV discovered in 1967 by Dr. Blumberg and colleagues •Dr. Blumberg awarded Nobel Prize in Medicine in 1976
WWW.HBVAdvocate.org
WWW.HBVAdvocate.org
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????
WWW.HBVAdvocate.org
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
WWW.HBVAdvocate.org
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
WWW.HBVAdvocate.org HBV is the second most important carcinogen after tobacco
WWW.HBVAdvocate.org
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
WWW.HBVAdvocate.org
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
WWW.HBVAdvocate.org
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 by 2 fold
WWW.HBVAdvocate.org
WWW.HBVAdvocate.org
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.mypyramid.gov
Treatment of Chronic HBV
WWW.HBVAdvocate.org
39
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.
WWW.HBVAdvocate.org
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 < 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 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
• •
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 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 ALT > ULN; HBV DNA > 2,000 IU/mL
• •
Q 3 mo ALT & HBV DNA Consider biopsy if persistent DNA elevation
•
or age >35 Treat if histology abnormal
• •
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
Compensated Decompensated HBV DNA <2,000 IU/mL HBV DNA ≥2,000 IU/mL Detectable HBV DNA Treat Undetectable HBV DNA Observe Observe or Treat Treat Wait List for Transplant
Keeffe EB.
Clin Gstroenterol Hepatol
. 2006;4:936-962.
Keeffe EB. Et al Clin Gastroenterol Hepatol. December 2008 http://www.cghjournal.org/inpress
WWW.HBVAdvocate.org
Approved HBV Medications
Generic Name Interferon alfa-2b Lamivudine Adefovir dipivoxil Entecavir Peginterferon alfa-2a Telbivudine Tenofovir Brand Name INTRON ® A EPIVIR-HBV ® HEPSERA ™ BARACLUDE ™ PEGASYS ® TYZEKA ™ VIREAD ™ Manufacturer Merck/Schering GlaxoSmithKline Gilead Sciences Bristol-Myers Squibb Genentech/Roche Idenix/Novartis Gilead Sciences Date Approved 1991 1998 2002 2005 2005 2006 2008
WWW.HBVAdvocate.org
HBV Drugs and Resistance
*Entecavir, peginterferon alfa-2a and tenofovir recommended as first line of treatment
WWW.HBVAdvocate.org
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 (2hrs prior to or 2hrs after a meal): BARACLUDE/entecavir • Monitoring during treatment
WWW.HBVAdvocate.org
Pregnancy Drug Categories
Drug
Tenofovir (Viread) Telbivudine (Tyzeka) Interferon (Intron A) Pegylated interferon alfa-2a (Pegasys) Pegylated interferon alfa-2b (PegIntron) Entecavir (Baraclude) Adefovir (Hepsera) Lamivudine (Epivir-HB)
Category
B B C C C C C C
Indication
HBV and HIV HBV HCV and HBV HCV and HBV HCV HBV HBV HBV and HIV
WWW.HBVAdvocate.org
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
WWW.HBVAdvocate.org
Recommended Websites
• HBV Advocate: www.HBVAdvocate.org
• CDC – Viral Hepatitis: www.cdc.gov/hepatitis/ • Hepatitis B Foundation: www.hbf.org
• www.hivandhepatitis.com