Hepatitis B- Hepatitis B- what GI nurses what GI nurses Need to KnowNeed to Know

Mary Pat Pauly MDMary Pat Pauly MDGastroenterology and Hepatology Gastroenterology and Hepatology

Kaiser Permanente Kaiser Permanente Clinical Professor of Internal Medicine and GI Clinical Professor of Internal Medicine and GI

at UC Davisat UC Davis

Hepatitis B Hepatitis B

EpidemiologyEpidemiologyModes of transmissionModes of transmissionHepatitis B vaccineHepatitis B vaccineNatural History Natural History Interpretation of serologyInterpretation of serologyIndications for treatment Indications for treatment Newer drugs available for treatmentNewer drugs available for treatmentImportance of Importance of ongoing follow up ongoing follow up

Hepatitis B Hepatitis B

EpidemiologyEpidemiology– Modes of Modes of

transmissiontransmissionRole of Hepatitis B vaccineRole of Hepatitis B vaccineNatural History Natural History Interpretation of serologyInterpretation of serologyIndications for treatment Indications for treatment Newer drugs available for Newer drugs available for treatmenttreatmentImportance of Importance of ongoing follow up ongoing follow up

Global Impact of Hepatitis BGlobal Impact of Hepatitis B

World PopulationWorld Population6 billion6 billion

2 billion with past / present 2 billion with past / present HBV infectionHBV infection

350–400 million with 350–400 million with chronic hepatitis Bchronic hepatitis B

15–40% develop 15–40% develop cirrhosis, liver failurecirrhosis, liver failure

or hepatocellular or hepatocellular carcinomacarcinoma

Worldwide: Worldwide: ~1 million / year die from HBV-associated liver disease ~1 million / year die from HBV-associated liver disease

United States: United States: Chronically infected ~1.25 million; ~5000 / year dieChronically infected ~1.25 million; ~5000 / year die

Korean Mummy Found With Korean Mummy Found With HBVHBV

Virus discovered in the Virus discovered in the liver of the South Korean liver of the South Korean Handong mummy Handong mummy – 500-year-old child500-year-old child– First time HBV ever been First time HBV ever been

found in a mummified body found in a mummified body

Study of the genome of Study of the genome of the 500-year-old virus the 500-year-old virus under way under way – To see if there have been To see if there have been

any significant changes to any significant changes to HBV over timeHBV over time

Source: Seoul National University

http://www.sciencedaily.com/releases/2007/07/070725093556.htm

Prevalence of HBV in immigrant Prevalence of HBV in immigrant populationspopulations

Prevalence reflects Prevalence reflects pattern of infection pattern of infection in country of originin country of origin– Africa 10 – 15%Africa 10 – 15%– Asia 10.4%Asia 10.4%– Eastern Europe 2-7%Eastern Europe 2-7%

Survey of Asian Am Survey of Asian Am populationspopulations– 23% in NYC*23% in NYC*– 11.1% in Chicago**11.1% in Chicago***Sherman A et al. Hepatology 2005;42:

214A**Cotler S et al. Clin Gastro & Hep 2009;7:776-80

Chronic HBV Prevalence: Asian Chronic HBV Prevalence: Asian Americans in San Francisco (2001-Americans in San Francisco (2001-

2006)2006)

Lin SY, et al Hepatology. 2007;46:1034-1040.

Chronic HBVPositive

At Risk: Lack ofProtective Antibodies

8.9%

Chronic HBV Positive,Unaware of Serostatus

65.4%

44.8%

Pre

vale

nce

(%

)

0

30

50

80

40

20

10

60

70

Transmission of HBV Transmission of HBV HBVHBV HCVHCV

IVDAIVDA commoncommon commoncommon

TransfusionTransfusion Before Before 19801980 Before 1992Before 1992

sexualsexual commoncommon uncommonuncommon

MSMMSM commoncommon rarerare

Vertical – mother Vertical – mother to baby to baby

Common Common

> 90% ->chronic > 90% ->chronic diseasedisease

< 5%< 5%

Child Child child child Africa 20 – 30% Africa 20 – 30%

chronic diseasechronic disease Tattoos, piercingTattoos, piercing possiblepossible possiblepossible

health care workerhealth care worker possiblepossible possiblepossible

28 year old nursing school colleague28 year old nursing school colleague– From TaiwanFrom Taiwan– In USA since age 10In USA since age 10

Applying for job at your hospitalApplying for job at your hospital– She was told to get HBV vaccineShe was told to get HBV vaccine– Requirement Requirement

Hepatitis B vaccine in employees who are not already Hepatitis B vaccine in employees who are not already immune to HBV immune to HBV

she was vaccinated when she went to nursing she was vaccinated when she went to nursing schoolschool– But HBsAB is neg.But HBsAB is neg.

What is your recommendation?What is your recommendation?

Hepatitis B vaccineHepatitis B vaccine

Recommended 3 doses at 0,1 and 6 monthsProtection– 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 OlderHIVchronic liver diseases diabetes obesesmokers

Two vaccines availableTwo vaccines available– Energix B – 20 mcgEnergix B – 20 mcg– Recombivax HB – 10 mcgRecombivax HB – 10 mcg

Acute HBV Infection Incidence* Acute HBV Infection Incidence* in the US (1982-2006)in the US (1982-2006)

Universal Universal vaccination vaccination of infants of infants recommended recommended in 1991in 1991

80% decline in 80% decline in incidenceincidence0

2

4

6

8

10

12

14

1982

1984

1986

Inci

den

ce

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

*Per 100,000 population.

MMWR: Surveillance Summary March 21, 2008 / Vol. 57 / No. SS—2.

Year

Risk factors for HBV in USRisk factors for HBV in US

other*Non IDMSMIDUHeterosexual

42%42%

18%18%

19%19%

16%16%

5%5%

CDC Sentinel Counties Study 1991-2006CDC Sentinel Counties Study 1991-2006

Case continuedCase continuedCheck further into history Check further into history – No FH of HBVNo FH of HBV

21 year old sister in LA who is healthy and without problems21 year old sister in LA who is healthy and without problems– Family history of mother who died at age 45 from Family history of mother who died at age 45 from

“cancer in the liver.”“cancer in the liver.”

Additional laboratory dataAdditional laboratory data– HBsAG positiveHBsAG positive– HBcAB positive HBcAB positive – HBsAB negativeHBsAB negative– ALT 20ALT 20

What can you tell her about her condition?What can you tell her about her condition?

Hepatitis B Hepatitis B

EpidemiologyEpidemiology

Modes of transmissionModes of transmission

Hepatitis B vaccineHepatitis B vaccine

Natural HistoryNatural History

Interpretation of serologyInterpretation of serology

Indications for treatment Indications for treatment

Newer drugs available for Newer drugs available for treatmenttreatment

Importance of Importance of ongoing ongoing follow up follow up

Spectrum of DiseaseSpectrum of Disease

Acute HBV infection

90% neonates 25–30% children

<10% adults

Progressive chronic hepatitis

Cirrhosis

HCCDeathDecompensated

cirrhosis

Inactivecarrier state

EASL Consensus Guidelines. J Hepatol 2003;Lok, McMahon. Hepatology 2004 (AASLD Guidelines)

Chronic infection

15–40%

Fulminant hepatic failure

~2%

Hepatitis BHepatitis B

EpidemiologyEpidemiologyModes of transmissionModes of transmissionHepatitis B vaccineHepatitis B vaccineNatural History Natural History

Interpretation of Interpretation of serologyserologyIndications for treatment Indications for treatment Newer drugs available Newer drugs available for treatmentfor treatmentImportance of Importance of ongoing ongoing follow up follow up

Hepatitis B terminologyHepatitis B terminology

There are three proteins expressed by the There are three proteins expressed by the Hepatitis B virusHepatitis B virus

Surface antigenSurface antigen– HBsAgHBsAg

Core antigenCore antigen– HBcAgHBcAg

Envelope antigenEnvelope antigen– HBeAgHBeAg

NameName AbbreviationAbbreviation DefinitionDefinitionHepatitis B Hepatitis B Surface AntigenSurface Antigen HBsAgHBsAg Protein found on the surface of virus, Protein found on the surface of virus,

indicates active infection. indicates active infection.

Hepatitis B Hepatitis B Surface AntibodySurface Antibody HBsAbHBsAb Antibody to the surface protein – confers Antibody to the surface protein – confers

immunity. Can be result of vaccination or immunity. Can be result of vaccination or past infection.past infection.

Hepatitis B Core Hepatitis B Core AntigenAntigen HBcAgHBcAg The core protein is inner structure of the The core protein is inner structure of the

virus and encloses the DNA. Found only in virus and encloses the DNA. Found only in the liver. the liver.

Hepatitis B Core Hepatitis B Core AntibodyAntibody HBcAbHBcAb Antibody to the core antigen is found in Antibody to the core antigen is found in

chronic hepatitis, resolved acute or chronic chronic hepatitis, resolved acute or chronic infection. NOT seen in those immune infection. NOT seen in those immune because of vaccine.because of vaccine.

Hepatitis B e Hepatitis B e AntigenAntigen HBeAgHBeAg This is a soluble protein detected when viral This is a soluble protein detected when viral

titers are high. Correlates with infectivity titers are high. Correlates with infectivity with the “wild type” HBV.with the “wild type” HBV.

Hepatitis B e Hepatitis B e AntibodyAntibody HBeAbHBeAb Antibody to the “e” Antigen. Can be seen in Antibody to the “e” Antigen. Can be seen in

inactive HBV, or chronic active hepatitis inactive HBV, or chronic active hepatitis secondary to a mutant: precore or core secondary to a mutant: precore or core promoter mutant. promoter mutant.

A few other termsA few other terms

ALT ALT alanine amino transferasealanine amino transferase

ASTAST aspartate aminotransferase aspartate aminotransferase

– Enzymes liberated by the liver when cells Enzymes liberated by the liver when cells injured and destroyed injured and destroyed

– Tests of liver injuryTests of liver injury

HBV viral load HBV viral load – Amount of virus measured in serumAmount of virus measured in serum

Measured in IU/mlMeasured in IU/ml

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.

Cirrhosis

Inactive Carrier

< 5%

Immune Tolerance

Early Childhood

> 95%

HBeAg-Chronic

Hepatitis B

Natural History of HBV Infection Natural History of HBV Infection

HBeAg+Chronic

Hepatitis B

Adulthood

Natural History of Hepatitis BNatural History of Hepatitis B

DynamicDynamic– Can go from Active Can go from Active inactive inactive active active

Liver disease on biopsyLiver disease on biopsy– can progress during periods of activity and can progress during periods of activity and

regress during periods of inactivity.regress during periods of inactivity.

HCC can occur HCC can occur – in patients with and without cirrhosisin patients with and without cirrhosis

Close clinical follow up is importantClose clinical follow up is important

Serology of HBVSerology of HBVInfectionInfection ALTALT HBeAGHBeAG Anti-Anti-

HBeAb HBeAb HBV DNAHBV DNA IU.mlIU.ml

histologyhistology

Immune tolerantImmune tolerant nlnl Pos+Pos+ Neg-Neg- HighHigh normalnormal

Chronic Chronic hepatitis hepatitis HBeAg +HBeAg +

upup Pos+Pos+ Neg-Neg- >20,000>20,000 activeactive

Inactive carrierInactive carrier nlnl Neg-Neg- Pos+Pos+ <2,000<2,000 normalnormal

Chronic Chronic hepatitis hepatitis HBeAg-HBeAg-

upup Neg-Neg- Pos+Pos+ >2,000>2,000 activeactive

Our colleague saw a gastroenterologist and had Our colleague saw a gastroenterologist and had additional tests ordered. additional tests ordered. She presents the following to you for interpretation: She presents the following to you for interpretation: – HBeAg positiveHBeAg positive– HBeAb negativeHBeAb negative– ALT 15, AST 16ALT 15, AST 16– Bilirubin, INR and platelet count – normalBilirubin, INR and platelet count – normal– HBV DNA –1,000,000 IU/ml 10 (6)HBV DNA –1,000,000 IU/ml 10 (6)– Alpha feto protein –normalAlpha feto protein –normal– Ultrasound of the liver – normal.Ultrasound of the liver – normal.

See AASLD guidelines – See AASLD guidelines – www.AASLD.org– This is exactly what is suggested in the AASLD guidelines for This is exactly what is suggested in the AASLD guidelines for

the evaluation of patients with HBV. One would also like to do the evaluation of patients with HBV. One would also like to do complete history. Rule out other causes of liver disease such as complete history. Rule out other causes of liver disease such as AIH, HCV and HIV. And hemochromatosis.AIH, HCV and HIV. And hemochromatosis.

Adapted from Lok AS, et al. Hepatology. 2007;45:507-539

The next question she asks The next question she asks

Is she a candidate for treatment?Is she a candidate for treatment?

Hepatitis B Hepatitis B

EpidemiologyEpidemiologyModes of transmissionModes of transmissionRole of Hepatitis B vaccineRole of Hepatitis B vaccineNatural History Natural History Interpretation of serologyInterpretation of serology

Indications for Indications for treatment treatment Newer drugs available for Newer drugs available for treatmenttreatmentImportance of Importance of ongoingongoing

follow upfollow up

Treatment of HBVTreatment of HBVCurrent Recommendations Current Recommendations

Monitor patients in Monitor patients in – Immune tolerant phaseImmune tolerant phase– Inactive –carrier stateInactive –carrier state

Consider treatment Consider treatment – Chronic Active hepatitisChronic Active hepatitis

Wild type – HBeAg positiveWild type – HBeAg positiveMutant type – HBeAg negative and HBeAb positiveMutant type – HBeAg negative and HBeAb positive

TreatTreat– Cirrhosis with active viral replicationCirrhosis with active viral replication

Consider: Consider: – Age, severity of liver disease, likelihood of response, Age, severity of liver disease, likelihood of response,

potential adverse eventspotential adverse events

ccc DNA….ccc DNA….nasty little viral formnasty little viral form

Does not replicateDoes not replicate

Impervious to nucleoside/tide Impervious to nucleoside/tide

analogue-based therapyanalogue-based therapy

Sits in cell for life of cellSits in cell for life of cell– up to 10 years in immune up to 10 years in immune

tolerant or inactive statetolerant or inactive state

Clearance based onClearance based on immune driven hepatocyte immune driven hepatocyte clearance clearance

or cell deathor cell death

Goals of treatment Goals of treatment

Suppression of HBV DNASuppression of HBV DNA– Goal is undetectableGoal is undetectable

Normal ALT Normal ALT – No inflammation or ongoing liver injuryNo inflammation or ongoing liver injury

Convert from active phase to inactiveConvert from active phase to inactive– HBeAG positive HBeAG positive negative and HBeAb pos. negative and HBeAb pos.

Holy GrailHoly Grail– HBsAg negative, HBsAb positive.HBsAg negative, HBsAb positive.

Hepatitis B – Hepatitis B – what every GI nurse what every GI nurse should knowshould know

EpidemiologyEpidemiologyModes of transmissionModes of transmissionRole of Hepatitis B vaccineRole of Hepatitis B vaccineNatural History Natural History Interpretation of serologyInterpretation of serologyIndications for treatment Indications for treatment Newer drugs available for treatmentNewer drugs available for treatmentImportance of Importance of ongoing follow up ongoing follow up

Treatment of HBVTreatment of HBV

Interferon alfa-2bInterferon alfa-2b

LamivudineLamivudine

AdefovirAdefovir

EntecavirEntecavir

Pegylated interferon Pegylated interferon alfa 2aalfa 2aTelbivudineTelbivudine

TenofovirTenofovir

199019901998199820022002

20052005

20052005

20062006

20082008

Treatment availableTreatment availableInterferon alphaInterferon alpha– Useful in select patients Useful in select patients

with HBVwith HBVGenotype A and BGenotype A and B

– Side effects significantSide effects significant

– No resistant mutants No resistant mutants

– MOAMOAAnti-viralAnti-viralDestroys infected Destroys infected hepatocytes hepatocytes

– Defined treatment Defined treatment duration duration

Nucleoside and Nucleoside and nucleotide analogsnucleotide analogs– Currently the Rx of choice Currently the Rx of choice

– Minimal SE Minimal SE

– Possibility of resistant Possibility of resistant mutantsmutants

– MOAMOASupresses but does not Supresses but does not eliminate the viruseliminate the virus

– Treatment indefiniteTreatment indefinite

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.

A, B, C,D, G

F

A, D, E

B, C

AG D

H, F

Global Distribution of the 8 HBV Global Distribution of the 8 HBV GenotypesGenotypes

D

A, B, C, D

Impact of HBV Genotype on Impact of HBV Genotype on Disease ProgressionDisease Progression

Genotype CGenotype C– severe liver diseasesevere liver disease– HCC HCC

Genotype BGenotype B– Seroconversion from HBeAg -> Seroconversion from HBeAg ->

anti-HBe at younger ageanti-HBe at younger age

Genotypes A and BGenotypes A and B– Increased response to Increased response to

Peginterferon alfa-2aPeginterferon 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

123456789

10111213141516

Treatment Treatment DrugDrug PotencyPotency ResistanceResistance FDA approvedFDA approved

LamivudineLamivudine ++++ 20% at 1 yr; 20% at 1 yr;

70% at yr 5 70% at yr 5

YesYes

AdefovirAdefovir ++ 3% at 2 yr3% at 2 yr

28% at 5 yr28% at 5 yr

YesYes

EntecavirEntecavir ++++++++ <2% at 4 yr*<2% at 4 yr*

YesYes

TenofovirTenofovir ++++++++ None yetNone yet yesyes

TelbivudineTelbivudine ++++++ 4% at one yr4% at one yr

11-25% at year 211-25% at year 2

yesyes

EmtricitabineEmtricitabine ++++ Similar to lamivudineSimilar to lamivudine Not yetNot yet

Hepatitis BHepatitis B

EpidemiologyEpidemiology

Modes of transmissionModes of transmission

Role of Hepatitis B vaccineRole of Hepatitis B vaccine

Natural History Natural History

Interpretation of serologyInterpretation of serology

Indications for treatment Indications for treatment

Newer drugsNewer drugs

Importance of Importance of

ongoing follow upongoing follow up

Importance of follow upImportance of follow up

To monitor for progression of diseaseTo monitor for progression of disease– To monitor those in inactive phases and To monitor those in inactive phases and – To recommend treatment in active phasesTo recommend treatment in active phases

Treament Treament – Monitor for efficacyMonitor for efficacy– Monitor for resistanceMonitor for resistance– monitor for toxicitymonitor for toxicity

To screen patients at high risk for HCC To screen patients at high risk for HCC regularly.regularly.

Chronic HBV: Chronic HBV: recommended followuprecommended followup

Immune – tolerant:Immune – tolerant:

1. Check ALT every 1. Check ALT every 3-6 3-6 months. months.

2. If ALT increases –2. If ALT increases –check HBV DNAcheck HBV DNAWork up further Work up further Consider treatment or Consider treatment or biopsybiopsy

3. Screen for HCC in high 3. Screen for HCC in high risk patientsrisk patients

--Inactive HBsAg Inactive HBsAg carriercarrier::

1. Check ALT every 1. Check ALT every 6 – 126 – 12 monthsmonths

2. If ALT increases2. If ALT increasesCheck HBV DNA Check HBV DNA work up furtherwork up furtherconsider biopsy and consider biopsy and treatmenttreatment

3. Screen for HCC in high 3. Screen for HCC in high risk patients.risk patients.

Screening for HCCScreening for HCC

Ultrasound and AFPUltrasound and AFP– AFP every 6 months and AFP every 6 months and – Ultrasound every 6 – 12 monthsUltrasound every 6 – 12 months

Screen high risk patients: Screen high risk patients: – Family history of HCCFamily history of HCC– men over 40, women over 50men over 40, women over 50– patients with chronic hepatitis with high viral patients with chronic hepatitis with high viral

load load – patients with cirrhosis. patients with cirrhosis.

““You can stab it with your You can stab it with your steely anti-virals but you just steely anti-virals but you just

can’t kill the beast.”can’t kill the beast.”

The EaglesThe Eagles

1977 – Hotel 1977 – Hotel CaliforniaCalifornia

Hepatitis BHepatitis B

with your help, with your help, we we

can do can do better…better…