Newer guidelines in the management of chronic hepatitis B

1. DIAGNOSIS AND MANAGEMENT OF CHRONIC HEPATITIS B INFECTION
Presented by: Dr. Himanshu Rana (JR-3)
Moderated by: Dr. S. K. SonkarMD (Assistant Professor)
Screeningpopulation
• Individual fromhigh/intermediateprevalenceareas
• Householdcontacts
• IV drug abusers
• PolygamousorH/O STD
• Men sex withmen
• Inmatesof correctionfacilities
• ChronicallyelevatedALT/AST
• HCV/HIV +ve
• Patientsonhemodialysis
• Pregnancy
• Immunosuppressive therapy
Prevention
• Carriersto be counseledforpreventionof transmission
• HBV negative contactsshouldreceive vaccination
• Pregnancy – Tenofovirin3rd
trimesterif DNA > 107
IU/ml to reduce transmission*
• Newbornstoreceive HBIgandvaccinationatdelivery
• Postvaccinationresponse testing
– Infantsof carrier mothersat 9 to 15 months
– Annually forchronichemodialysispatients
AssessmentofHBV positive subjects
• Primarycare invetigations
– HBeAg/anti HBeAg
– HBV DNA level
– Anti HCV
– Anti HDV
– Anti HIV
– IgG HAV
– ALT/AST/GGT/serumalbumin/total bilirubin/PT/full bloodcounts
• Secondarycare investigations
– Transientelastography
– Liverbiopsy
Goalsof treatment
• Preventionof long-termnegativeclinical outcomes(eg,cirrhosis,HCC,death) bydurable
suppressionof HBV DNA
• Remissionof liverdisease
• Primarytreatmentendpoint
– Sustaineddecrease inserumHBV DNA leveltolow orundetectable
• Secondarytreatmentendpoints
– Decreasedornormalize serumALT
– Induce HBeAglossor seroconversion
– Induce HBsAglossor seroconversion
– Improve liverhistology

2. Management(adults)
Childrenand young people
• DNA levels>2000 IU/ml / abnormal ALT– liverbiopsy*
• Whento start!!!
– DNA levels>2000 IU/ml / abnormal ALT* or
– Significantfibrosisonbiopsy
• METAVIR stage ≥ F2 or
• Ishakstage ≥ 3
• Fibroscanisnot recommendedinchildren
Treatment sequence**
• Peginterferon α-2ainitial treatmentinall*
• TenofovirandEntecavirassecondline inall*
• Prophylaxistobe startedbefore startingimmunosuppressivetherapyandcontinue till 3
monthsaftersero-conversion
* Exceptinpregnancy,breastfeeding,decompensatedchronicliverdisease
** NICEclinical guidelines,The GuidelinesManual,June 2013; 9-10
• Telbivudine &Adefovirnotrecommended
• If alreadyon Adefovir– continue aspertreatingphysician
• If alreadyon Telbivudinechange to
– Entecavirfor-ve h/o lamivudine resistance
– Tenofovirfor+ve h/oof lamivudine resistance
Whento ConsiderPegIFN?
• Favorable predictorsof response[1,2]
– Low HBV DNA

3. – HighALT
– Genotype A or B > C or D[3-5]
• Specificpatientdemographics[1,2]
– Generallyyoungpeople
– Absence of comorbidities
• Patientpreference[1,2]
• ConcomitantHCV infection
DefinitionofResponse to Antiviral Therapy
Response Definition
Primary nonresponse* ↓ inserum HBV DNA by < 2 log10 IU/mL after≥ 24 wks of therapy
Biochemical response ↓ inserum ALT to withinthe normal range
Virologicresponse
↓ inserum HBV DNA to undetectable levelsbyPCRand
loss ofHBeAg in patients who were initiallyHBeAgpositive
Virologicrelapse
↑ inserum HBV DNA of1 log10 IU/mL after discontinuationof
treatment in≥ 2 determinations> 4 wks apart
Histologicresponse
↓ inhistologyactivity indexby ≥ 2 pointsand
no worseningof fibrosisscore compared to pretreatmentliverbiopsy
Complete response Fulfill criteriaof biochemical and virologicresponse and HBsAg loss
First Line therapy
Decompensatedliverdisease

4. • HepatitisB+C co infection→ Peg IFN+ Ribavirin
• HepatitisB+D co infection→ PegIFN for 48 weeks → Continue treatment& evaluate
response annually
(considerstoppingtreatment ifno↓ inHDV RNA after 24 – 48weeks)
Managementof PatientsWithHIV Coinfection
• HBV/HIV-coinfectedpatientswhorequire HBV therapyshouldbe treated[1]
– Liverbiopsyshouldbe consideredinpatientswith fluctuatingormildlyelevatedALT
(1-2 x normal)
Not on HAART or not Anticipated
to Antiretroviral Therapy*
PlanningAntiretroviral
Therapy (HBV+HIV)
AlreadyReceivingAntiretroviral
Therapy
 Antiviral therapythatdoesnot
target HIV,eg:pegIFN or ADV
or entacavir
 Althoughtelbivudinedoesnot
target HIV, shouldnotbe used
 That are effectiveagainst
bothviruses:( TDF+ LAM)
0R (Emtricitabine+TDF)
preffered
 If regimendoesnotinclude drug
active againstHBV,may be treated
withpegIFN, ADV orentacavir.
 If LAM resistance,addTDFor
adefovir
Childrenand young people
2nd
line therapy

5. Prophylaxisin immunosupressive therapy
PRE-EXPOSURE PROPHYLAXIS
RecombivaxHB Dose (mcg) Engerix-BDose (mcg)
Infantsandchildren (<11 yearsof age) 0.5 ml (5) 0.5 ml (10)
Adolescents11-19 years 0.5 ml (5) 0.5 ml (10)
Adults>20 years 1.0 ml (10) 1.0 ml (20)
Post-exposure prophylaxsis
• Perinatal exposure of infants: single dose of HBIG,0.5 mL, IMin thigh immediately after
birth,followedbycompletecourse of three injectionsof recombinanthepatitisBvaccine to
be startedwithinfirst12 hours of life.
• Directpercutaneousinoculationortransmucosal exposure toHBsAg-positive bloodorbody
fluids: single IMdose of HBIG, 0.06 mL/kg,as soon as possible, followedbycomplete
course of hepatitisBvaccine withinthe firstweek.
• For those exposedby sexualcontact: single IMdose of HBIG, 0.06 mL/kg,within14 days of
exposure,followedby complete course of hepatitisBvaccine.

6. Managementof Antiviral-ResistantHBV
Treatment Strategy
Lamivudine resistance
 Add adefovirortenofovir
 Stop lamivudine andswitchtotenofovir/emtricitabine
Adefovirresistance
 Add lamivudine
 Stop adefovirandswitchtotenofovir/emtricitabine
 Switchto or add entecavir
Entecavirresistance  Switchto tenofovirortenofovir/emtricitabine
Telbivudine resistance
 Add adefovirortenofovir
 Stop telbivudineandswitchtotenofovir/emtricitabine
Tenofovirresistance  May add entecavir,telbivudine,lamivudine,oremtricitabine
Preventionand Monitoringof Resistance
Prevention
Avoidunnecessarytreatment
Initiate potentantiviral thathaslowrate of drug resistance oruse combinationtherapy
Switchto alternative therapyinpatientswithprimarynonresponse
Monitoring
Testfor serumHBV DNA (PCR) every3-6 mosduringtx
Checkfor medicationcompliance inpatientswithvirologicbreakthrough
Confirmantiviral resistance withgenotypictesting
Screeningfor HCC
• Highrisk to be screenedevery6-12months – USG
• AFP is usedwhere USG isnot available
• HIGH risksubjects
– Asianmenover40 yrs age
– Asianwomenover50 yrs age
– Cirrhotics
– Family historyof HCC
– Africansover20 yrs age
– Anycarrier >40 yrs withDNA >2000 IU/ml or intermittentorpersistentALTelevation

7. Questions
1. Whichof the followingdrugshave beensuggestedasfirstline therapyasperthe EASLD
guidelines2012 for the managementof chronichepatitisB?
a. Tenofovir
b. Adefovir
c. Interferonalpha
d. Peg-IFN alpha
ANS:d
2. Whichof the followingdrugsisan absolute contraindicationforPeg-IFN alphatherapy?
a. Chronicrenal failure
b. Treatedpulmonarytuberculosis
c. Ischemicheartdisease
d. Decompensatedliverdisease
Ans:d
3. Whichof the followingrelatedtohepatitisBinfectionistrue?
a. Around99% cases of infectionresolve afteranepisodeof acute hepatitis
b. NewborntoHBsAgpositive mothersdeveloplife threateningfulminanthepatitis
c. IgMantiHBc is alwaysnegative inacute reactivationof chronichepatitisBvirus
d. Patienttobe startedon immunosuppressive therapyare notrequiredforscreening
of HepB infection
Ans:c
4. Whichof the followingisfalse?
a. Fibroscanmeasuresthe stiffnessof liverinkilopascals bymeasuringthe shearstress
produced.
b. Fibroscanscores of >11kpa are diagnosticof significantfibrosis
c. Liverbiopsyshouldbe usedinpatientswithscore >11kpafor guidingtherapy.
d. All patientswithchronichepatitisBrelatedliverdisease mustbe subjectedto
fibroscan.
Ans:c
5. Whichof the followingisnotcorrect regardingtreatmentof hepatitisBinfection?
a. Tenofovircanbe usedas 2nd
line treatmentinall chronicHepBinfectionregardless
of HBeAgstatus.
b. Firstline therapyof IFN alphashouldbe usedinall indicatedHeatitisBpatientsfor
at least24 – 48 weeksbefore switchingto2nd
line therapy
c. Tenfovirshouldbe usedinpatientwithhistorypositiveforlamivudineresistance
d. Ribavirin shouldbe addedtoPegIFN alphainpatientswithHepatitisCcoinfectionas
firstline treatment.
Ans:b