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Journal of The Association of Physicians of IndiaVol. 63November 2015 43

Management of Chronic Hepatitis B Infection in

IndiaDeepak N Amarapurkar1, Kaushal Madan2, Dharmesh Kapoor3

R E V I E W A R T I C L E

1Consulting Gastroenterologist and Hepatologist, Department of Gastroenterology and Hepatology, Bombay

Hospital and Medical Research Centre, Mumbai, Maharashtra; 2Senior Consultant, Gastroenterologist and

Hepatologist, Department of Gastroenterology, Medanta Medicity, Gurgaon, Haryana; 3Senior Consultant,

Hepatology, Department of Gastroenterology, Global Hospital, Hyderabad, Telangana

Received: 22.01.2015; Accepted: 07.04.2015

Overview of Chronic

Hepatitis B Infection

Chronic hepat i t i s B (CHB)infection is a significant healthproblem world wide with Indiacategorized into intermediatezone of prevalence.1 Consideringan average carrier rate of 5% the

total number of HBV carriers in thecountry was estimated to be about50 million. Unlike in other parts ofAsia, horizontal transmission, viaintra-familial transmission is themain route of HBV transmission

in India.2

Genotypes A and D are prevalentin the Indian subcontinent but a

changing trend is being witnessedwith emergence of genotypes B, E,F and G, which could be attributed

to immigration, trafficking and use

based on geographical locations,type of transmission and genotypes.The sustained clinical remission

(inactive phase) and longer inactivestate with low HBV DNA (


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Journal of The Association of Physicians of IndiaVol. 63November 201544

Fig. 1: Transmission and natural history

tenofovir (TDF)] . Def in i t ionsof some common terminologiesand diagnostic criteria have beenelaborated in Table 1.

Recommendations forManagement in India

Several professional societiesl ike the American Association

for the Study of Liver Diseases(AASLD), the European Associationfor the Study of the Liver (EASL)and Asian Pacific Association forthe Study of the Liver (APASL)

have developed guidelines to assistphysicians in the management of

CHB patients. These guidelines areflexible and the recommendations

put forth by them may be appliedby the physic ians in view of it sapplicability in a given situation.

P r a c t i c i n g m o s t o f t h e s e

r e c o m m e n d a t i o n s m a y b echallenging in resource-limitedsettings like India. Bristol-MyersSquibb (BMS) has del iberatedan educational initiative, PATH

(Professionals Acting Togetheron Hepatitis) to help physicians

address the challenges faced in

the diagnosis and management ofCHB patients. An India specificconsensus statement was developed

ba se d on the fe ed back given byexperts in the field of hepatology

to questionnaire on evaluation andmanagement of CHB includingspec ia l ca tegories as wel l asborderline cases. An educationalmodule developed based on all the

guidelines and expert consensuswas also presented in a continuingmedical education forum.

T h i s a r t i c l e r e v i e w s

recommendations of the threeprofessional society guidelines

(AASLD, EASL and APASL andprovides recommendations of

Indian experts.

A. Management of CHB

Counseling and Prevention ofTransmission

E d u c a t i n g p a t i e n t s a n d

spreading awareness about HBVinfection is crucial for successfulantiviral therapy and can curb thespread of this infection. Publishedguidel ines recommend proper

counseling of patients on preventionof transmission of HBV, advice onlifestyle (activity, diet, alcohol use,

etc.) and other predisposing factorsas well as vaccination of high riskpatients (sexual and household

members in close contact withpatients/ carriers, HBsAg positive

mothers , hea l thcare workers ,dialysis patients, incarceratedpatients, etc.). Additionally, useof hepatitis B immune globulin(HBIG) is advocated for infants

bor n to in fe ct ed mo the rs al on gwith hepatitis B vaccine (at deliveryfollowed by complete vaccinationseries).4,12,13 Experts in India suggestat least two sessions of counseling,one at initial visit and the other

after investigations with focus onalleviating undue anxiety of thepatient. The main discussion pointsinclude stage of the disease and itsprognosis, prevention of disease

transmission, available treatmentoptions, their side effects andthe importance of compliance totherapy.

Initial Evaluation of Newly

Diagnosed Patients

Initial evaluation, advised by all

guidelines, allows staging of thedisease and further assesses theneed for treatment and surveillance.It should include medical history,

physical examination, laboratoryinvestigations [liver profile, liverimaging and viral markers (HBeAg,HBeAb, IgM anti-HBc, HBV DNA

load)] to assess liver disease andHBV replication status. In additionto this, Indian experts also suggestobtaining information on family

history of HCC/cirrhosis which isa risk factor for advanced disease.

Decision to Treat

Serum HBV DNA, serum ALT

levels and liver disease stage (basedon liver biopsy and/r non-invasivemarkers of fibrosis and/or imaging)are the cr i ter ia for t rea tment

initiation, however, the cut-offvalues and the need for liver biopsyprior to treatment initiation differsamong the guidelines (Table 2). Inline with the global guidelines,

VerticalTransmission

*HorizontalTransmission

Immune TolerantPhase

HBeAg +ve,

HBV DNAnormal ALT &absent to mild liver

inflammation

Immune ClearancePhase

HBeAg +ve,HBV DNAALT & moderate to

severe liverinflammation

Inactive PhaseAnti-HBe +ve,undetectable

HBV DNA, normal ALT& near-normal histology

Sero-conversionAnti-HBs +ve

undetectable HBV DNA& normal ALT

*Immune tolerant phase is very short in case of horizontal transmission

Sero-reversionHBeAg +ve,HBV DNA

&ALT

Reactivation toHBeAg -ve CHB

Anti HBe +ve, fluctuatingHBV DNA, fluctuating ALT

&liver inflammation


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Table 1: Definitions and Diagnostic Criteria

Denitions

Biochemical response Biochemical response is dened as normalization of ALTlevels

Serological response for HBeAg Serological response for HBeAg applies only to patients withHBeAg-positive CHB and is dened as HBeAg loss with

seroconversion to anti-HBe.Serological response for HBsAg Serological response for HBsAg applies to all CHB patientsand is dened as HBsAg loss with development of anti-HBs

Histological response Histological response is dened as decrease innecroinammatory activity without worsening in brosiscompared to pre-treatment histological ndings.

Complete response Complete response is dened as sustained o-treatmentvirological response together with loss of HBsAg

Virological response Virological response is dened as undetectable levels of HBVDNA and loss of HBeAg in patients initially HBeAg positive

Primary non-response Primary non-response is dened as decrease in serum HBVDNA by < 2 log10 IU/mL after at least 24 weeks of therapy incomplaint patient

Virologic relapse Virologic relapse is dened as increase in serum HBV DNA

of 1 log10 IU/mL after discontinuation of treatment in at least2 determinations more than 4 weeks apart

Virologic breakthrough Increase in HBV DNA by >1 log10 above nadir afterachieving virologic response, during continued treatment

Viral rebound Increase in serum HBV DNA to > 20,000 IU/mL or abovepre-treatment level after achieving virologic response, duringcontinued treatment

HBeAg reversion Reappearance of HBeAg in a person who was previouslyHBeAg-negative, anti-HBe-positive.

Biochemical breakthrough Increase in ALT above upper limit of normal after achievingnormalization, during continued treatment

Genotypic resistance Detection of mutations that have been shown in invitro studies to confer resistance to the NA that is beingadministered

Phenotypic resistance In vitroconrmation that the mutation detected decreases

susceptibility (as demonstrated by increase in inhibitoryconcentrations) to the NA administered.

Hepatic decompensation Signicant liver function abnormality as indicated byraised serum bilirubin and prolonged prothrombin time oroccurrence of complications such as ascites.

Hepatitis are Abrupt increase of serum ALT

Undetectable serum HBV DNA Serum HBV DNA below detection limit of a PCR-based assay

Diagnostic criteria

Chronic hepatitis B 1. HBsAg+ve for > 6 months

2. Serum HBV DNA:

HBeAg+ve: >20,000 IU/mL

HBeAg-ve: 2,000-20,000 IU/mL

3. Persistent or intermient elevation in ALT levels

4. Liver biopsy: Mild/Moderate/severe necroinammationInactive carrier state 1. HBsAg+ve for >6 months

2. HBeAg-ve and anti-HBe +ve

3. Serum HBV DNA 20,000 IU/ml.4,12

EASL recommends cut-off of HBVDNA >2000 IU/ml in patients over30 years of age and/or with a familyhistory of HCC or cirrhosis.13

Horizontal transmission beingprevalent in the country, advanceddisease sets in around the age of 40

years with higher chances of HBeAg-negative disease. Therefore, expertsadvocate liver biopsy wheneverthere is uncertainty about initiatinga treatment based on laboratory

investigations especially in patientsabove 40 years.

Monitoring and Decision to StopTreatment

All patients on CHB therapysho u l d be c l o se l y m o ni to re dfor response, tolerabil i ty and

adherence to treatment. Experts


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Table 2: Recommendations for Treatment Initiation

Parameters Recommendations of Guidelines

HBeAg HBV DNA(IU/ml)

ALT EASL (2012)13[UL: DNA= 2000 IU/ml;ALT= 40 IU/ml]

APASL (2012)4[UL: DNA= 20,000 IU/ml;ALT= 40 IU/ml]

AASLD (2009)12[UL: DNA= 20,000 IU/ml;ALT= 30 (men) and19 (women) IU/ml]

Indian experts[UL: DNA= 2000 IU/ml;ALT= 40 IU/ml]

Positive > 2000 < ULN Monitor 3-6 months.Liver biopsy andtherapy if age > 30 yearsor family h/o HCC.Treat if moderate orgreater inamation

Monitor (3-6months) Monitor 3-6months;frequent monitoring if ALTbecome elevated

Liver biopsy if age >40years, ALT persistently highnormal or family history ofHCC and then decide

Monitor 3 monthly ALTfor at least one year;treat if ALT level rises. Ifuncertainty exists (becauseof uctuating ALT orDNA, family history ofHCC, etc) biopsy can beadvised.

Liver biopsy if age >40years; treat if moderate orgreater inamation

Positive > 2000 > ULN Monitor 3-6 months.Liver biopsyrecommended.Treat if moderate orgreater inamation

Liver biopsy if age >40years.Treat if moderate orgreater inamation

If HBV DNA >20000, ALT1-2 X ULN and age >40 yrs.then consider liver biopsy todecide treatment

Monitor 3 monthly ALTfor at least one year;treat if ALT level rises. Ifuncertainty exists (becauseof uctuating ALT or

DNA, family history ofHCC, etc) biopsy can beadvised

Liver biopsy if age >40years; treat if moderate orgreater inamation

Positive > 20,000 > 2 X ULN Start treatment withoutbiopsy

Treat if persistent ALT(3-6months)/ concern fordecompensation.If DNA 2 X ULN Not applicable Treat if ALT persists

or concern fordecompensation

Treatment may be

considered particularly ifthey are older patients orthose with cirrhosis

Treat

Negative > 20,000 > 2 X ULN Start treatment withoutbiopsy

Treat Treat if persistent Treat

ALT: Alanine transaminase; HBV DNA: Hepatitis B virus deoxyribonucleic acid; UL: Upper limit; ULN: Upper limit of normal

world over consider normalizationof serum ALT levels, decrease inserum HBV DNA level, loss ofHBeAg, HBeAg seroconversionand HBsAg loss to be important

response indicators. For patientson IFN therapy, HBV DNA levels

should be monitored every 3 to

6 months ; in HBeAg-posi t ivepatients, the HBeAg /anti-HBeAgstatus is to be monitored every 6months as per the American andEuropean guidelines12,13 while theAPASL advocates a more frequent3 monthly monitoring.4 If treated

with a NUC, liver panel should be

performed every 3 months whereasHBV DNA levels and HBeAg/anti-HBeAg status need monitoringevery 3 to 6 months.

For their known side effects,patients on IFN therapy requirefrequent monitoring of blood


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Table 3: Recommendations for Termination of Treatment

GuidelineNon-cirrhotic patients Compensated cirrhosis Decompensated

cirrhosisHBeAg positive HBeAg negative HBeAg-positive HBeAg-negative

AASLD (2009)12 HBeAg seroconversion andundetectable serum HBVDNA and completed at

least 6 months additionaltreatment after appearanceof anti-HBe

HBsAg clearance HBeAg seroconversion andcompleted at least 6 monthsof consolidation therapy

HBsAg clearanceand completed atleast 6 months of

consolidation therapy

Life-longtreatment

EASL (2012)13 HBsAg clearanceORHBeAg seroconversionwith HBV DNA 50 years. Expertsprefer US however do not deny AFPas a survelliance tool.

P a r t i a l R e s p o n s e / N o n -

Response / Breakthrough

Frequently viruses undergo

mutations which can decrease

the re sp o nse to NUCs . No n-compliance to these agents isthe main reason for mutations

which may further result in partialresponse, no response or viral

breakthrough. Physicians suggestassessing compliance of patientswith primary non-response to any

NUC. Genotyping of HBV strains incompliant patients with a primarynon-response or viral breakthroughm a y h e l p i n f o r m u l a t i n g arescue strategy. In patients with

primary non-response to ADV,


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a rapid switch to TDF or ETV isrecommended. Patients with partialresponse to LAM/LdT (at week24)/ADV (at week 48) or with viral

breakthrough may be swi tched to

ETV/TDF. It is advisable to get 3

monthly DNA for the first yearas it is the indicator of responseas well as compliance. Treatmentwith same antiviral agents may

be continued in patients withdeclining HBV DNA levels if thereis an increase in viral response anda low risk of resistance with longterm therapy (drugs with higher

genetic barrier to resistance, suchas entecavir or tenofovir will havelower risk of resistance with longterm therapy).

B . M a n a g e m e n t o f S p e c i a l

Population

Pediatric Population

HBV infection in children ismostly asymptomatic and thereforethe disease burden is likely to be

underappreciated; there is limitedinformation on CHB in Indianchildren. According to a clinicstudy conducted in 460 childrenof different age groups in north

India, 4.35% tested HBsAg-positivewith highest (6.09%) prevalencein 1-4 years of age and the leastin 10-14 years age group.16 Fewother studies, assessing HBsAgpositivity, revealed that prevalencevaries in different regions in India

and the overall positivity rangesfrom 1.3-12.7%.17 Most childrenwith HBV infection are consideredto be in the immunotolerant phasewhen treatment is not indicated.

All guidelines view children with

overt hepatic decompensation ascandidates for treatment. Childrenwith elevated ALT levels should beobserved for spontaneous HBeAg

seroconversion before initiatingtreatment with IFN and LAM. Ingeneral a conservative approach iswarranted in children because ofapparent lack of long term benefits

and the risk associated with drugtherapy.

Pregnancy

HBV infection can affect the

outcome of pregnancy leading to

spontaneous abortion, stillbirth orprematurity in addition to risk ofvertical transmission. Studies fromdifferent parts of the country haverevealed a prevalence of 0.9 to 9%

of HBsAg positivity in pregnantwomen.18,19IFN-based therapy may

be preferred for women who wish

to conceive in future and wish to trya finite duration therapy in orderto become HBV negative before

becoming pregnant , although thechances of achieving this result are

very low. Pregnant women with alow HBV viral load do not requireimmediate treatment; passiveimmunization and active HBVvaccination of the newborn reduces

chance of acquiring infection insuch cases. Antiviral therapy inpregnancy could be limited topat ients wi th high HBV vira lload; therapy is advised during

third trimester of pregnancy andshould be continued for atleast12 weeks after delivery in orderto reduce the r i sk of motherto chi ld transmission. 20 IFN iscontraindicated during pregnancyand Category B drugs such as LdT

or TDF are recommended. Womenwho have significant liver disease

may continue anti-viral treatmentthroughout their pregnancy and forlong duration even after delivery(such patients themselves have anindication for anti-viral therapy.

However, safety of these drugs hasnot been established in breast-fedinfants.

Hepatic Decompensation

A l l g u i d e l i n e s a d v o c a t e

prompt initiation of treatmentusing NUCs in patients with liverdecompensation regardless of HBVDNA levels; this will lead to clinicalstabilization and will minimizethe need of transplant. IFN is

contraindicated in this settingbecause of the r isk of seriousbac te ri al in fe ct io n an d po ssi bl eexacerbation of l iver disease.Potent NUCs with good resistance

profile such as ETV or TDF arepreferred. EASL recommends dose

adjustment of all NUCs in patients

with low creatinine clearance (


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treatment outcomes with TDF/LAM.24

I m m u n o s u p p r e s s i o n /Chemotherapy

R e a c t i va t i o n o f HBV wi thincrease in serum HBV DNA andALT level has been reported in

20-50% of HBV carriers receivingimmunosuppressive or cancerchemotherapy. 12 Screening andvaccination of HBV seronegative

patients is highly recommended.Pre-emptive oral antiviral therapyis advocated for HBsAg-positivepat ients and HBsAg-negat ivepatients with detectable HBV

DNA levels; treatment should becontinued for at least 12 months after

cessation of immunosuppressivetreatment. HBsAg-negative patientswith antibodies against HBV core

protein (anti-HBc) but undetectablese ru m HBV D NA sho u l d befollowed carefully by means of ALTand HBV DNA testing regardlessof anti-HBs status and should be

treated with NUC therapy uponHBV reactivation even before ALTelevation is evident. Treatmentguidelines recommend protection

of at-risk patients with NUC of high

antiviral potency and low risk ofresistance.

Co-morbidities

N u c l e o t i d e / n u c l e o s i d eanalogues are cleared by the kidneyswith nucleotide analogues having

more nephrotoxic potential. Serumcreatinine levels and estimatedcreatinine clearance should bedetermined before starting NUCin all patients. High renal risks

include decompensated cirrhosis,

creatinine clearance 2 times ULN.Studies have however shown thata substantial proportion of CHB

patients with marginally elevatedor persistently normal ALT whoremain ineligible for therapy havesignificant histological damage.25Management of such patients

should be individualized based onliver histological status. Treatmentcan be deferred in patients whoshow minimal necroinflammationand mild (stage 1) fibrosis. Liver

bio ps y pr ov id es mo re se nsi tiveand specific information on liverdisease progression. However,liver biopsy is invasive and carriesa risk of complication, albeit low.

The limitations of liver biopsy can

be overcome by use of a rapid, non-invasive transient elastography(Fibroscan); a study by Goyal etal, revealed that fibroscan could

avoid liver biopsy in 70% patientswith an accuracy > 90% in CHBpatients. 26 However, owing toresource constraints, faci l i t ies

of biopsy or fibroscan may beunavailable and in such situationsa risk impact assessment scorealong with the HBV DNA levelmay be useful to guide treatment

decisions. A similar risk impact

score is deduced based on age,

gender, ALT levels, BCP mutations,HCC in first-degree relatives andthose with low albumin/plateletvalues for cirrhosis. In this system,

a numerical score has been assigned

for each risk factor and if the score is3 and the HBV DNA is > 2,000 IU/mL, treatment is advised.27Experts

have recommended AST/ALT ratioreversal (even if ALT is marginallyraised), low albumin, low plateletcount and mild splenomegaly onUSG as useful indicators of fibrosis

in India; presence of such indicatorsshould reduce the threshold fordoing a liver biopsy.

P a t i e n t s w i t h m a r g i n a l l y

elevated or persistently normalALT may be categorized based onthe HBeAg status and HBV DNAlevels to strategize management

(Figure 2).

HBeAg Posi tive Patients

Those with marginally elevatedALT and/or HBV DNA 40 years of age. However,

age of treatment initiation shouldbe reduced in those with positivefamily history for HCC.28

HBeAg Negative Patients

Those with marginally elevated

ALT and/or HBV DNA between2 ,000 and 20 ,000 IU/mL needclose monitoring with a l iver

biopsy before initiating therapy.Patients with PNALT and/or HBV

DNA >2000 IU/mL need frequentmonitoring of ALT.28


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Barriers to Effective

Management in India

Important factors that need to be

taken into account for optimizationof anti-viral therapy include theseverity of liver disease, durationof recommended therapy, rapidityof action and the adverse effect

profile of the drugs. Emergenceo f dru g re s i s ta nc e wi th o ra lantiviral agents is also a majorchallenge confronting clinicians.Thus, prevent ion of ant ivi ra l

drug resistance and appropriatemanagement of viral breakthroughi s a n a dde d t re a tm e nt g o a l .Guidelines recommend selection

of drugs with high potency andlow risk of resistance; thereforemost guidelines advocate initialtreatment with ETV, TDF or peg-IFN.4,12,13

There is insufficient safety andefficacy data on antiviral agentsin India. 29-31 Few studies have

reported positive outcomes withantivirals. ETV has been associatedwith significantly higher rates ofserological, viral and biochemicalimprovement with no resistance

o b s e r v e d u p t o 4 0 w e e k s o ftreatment.32,33ADV was found to be

less potent though the frequency ofresistance mutations was low.31TDFand LdT were reported to reversedecompensat ion and improve

hepatic functional status withsignificant reduction in HBV DNAlevels.34-36LAM-resistant mutationsobserved in 27% patients, werestrongly associated with longertreatment duration.37

Though all approved agents areavailable in India, treatment withguideline recommended first-line

agents is a challenge, the majorhurdle being unaffordability dueto high cost of therapy. The cost

of oral anti-viral therapy rangingfrom 76 to 1707 US$ for CHB/compensated cirrhosis, to 15,000US$ for HCC patients and may be ashigh as 20,000 US$ in patients withdecompensated cirrhosis.38Due to

cost constraints, patients eitherdiscontinue therapy or skip/splitthe dose, delay refills, avoid newprescriptions or use generics. Thisresults in inadequate management

and increases the risk of resistance/virologic breakthrough.39,40 Thus,

in countries like India with low

p e r c a p i ta i nc o m e , p a t i e nt sp r e f e r e n c e a l s o b e c o m e s a nimportant factor in deciding drugtherapy. The advocated first lineagents may therefore have to be

substituted with cost-effective

older agents or combinat ionsthereof .29-31 Jayakumar, et al intheir study have demonstrated

comparable ef f i cacy of LAM/ADV combination with ETV andTDF as monotherapy.41Thereforefor patients with compensatedcirrhsois, ETV, LdT, TDF or their

combinations, whereas for othersa LAM/ADV combination can be agood alternative to more expensivefirst line treatments. Similarly inchronic hepatitis with or without

grade II f ibrosis-monotherapywith either TDF or ETV or LdTor IFN can be recommended inpatients who can afford wherasmonotherapy wi th LAM may

be ad vi se d in ot her s with cl osemonitoring of viral breakthroughor non-response.

In India, ETV, LdT and TDFcan be recommended in compliantpatients who can afford goodt r e a t m e n t w h i l e L A M / A D V

combination may be advised fornon-affording patients with wellcompensated cirrhosis while LAMalone may be advised in thosewith grade II fibrosis. De-novocombination is advised in fibrotic

patients with high viral load (Table4).

The cost constraint, together

with lack of awareness of disease,lack of screening programs, socialstigma, limited resource allocation

(laboratories / staff and HCPs),and sub-optimal management and

limited reimbursement of drugs/tests are other obstacles to effectivemanagement of CHB in India.

Conclusions

This article serves as guidanceto clinicians while formulatingstrategies for management of CHBpatients in India. Experts haveadapted recommendations of the

three international guidelines.

Fig. 2: Recommendations for borderline cases

Marginally

ElevatedPersistently

Normal

HBeAg

NegativePositive

< 20,000 NA 2000- 20,000 > 2000

Marginally

ElevatedPersistently

Normal

Follow-up 6-12months

Biopsy mandatoryfor increasing/stableHBVDNA over6months or age>40 yrs or family h/ohepatocellular

carcinoma

Treatment may helpif ALT levelsbetween 1 & 2 ULN

Treat patients>40 years ofage

Treat 40 yrs/family h/o HCCand beforeinitiatingtherapy

Biopsy mandatory

Do not treat ifminimal necro-inflammation withHBV DNA > 20,000IU/ml

Monitor ALT 3-4times/ year & HBVDNA once/year

HBV

DNA

ALT

Levels

Recomme-

ndations


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However, commendations likesubstituting biopsy with cirrhosisscore and potent expensive drugs

with cost effective combinationtherapy will be appropriate inmanagement of CHB in resourcelimited Indian setting.

Acknowledgements

Professional medical writingsupport and editorial assistance

was provided by DiagnoSearchLife Sciences (P) Ltd., funded byBristol-Myers Squibb.

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Table 4: Recommendations of Treatment for Indians

Liver status HBeAgstatus

HBV DNAlevels

(copies /ml)

Therapy Monitoring

Aordable and/orcompliant

Compensatedliver disease

Positive >5 logs ETV/LdT/IFN 3 monthly for HBV DNA

Compensatedliver disease

Negative >3 l ogs Monotherapy:ETV/LdT

3 monthly for HBV DNA

Combination therapy

LAM + TDF OR

LdT + TDF OR

ETV + TDF

6 monthly for HBV DNA

Compensatedcirrhosis

Positive/Negative

>3 log and 9 logs LdT / ETV / TDF -

Fibrosis(grade II)

Positive 9 logs ETV/IFN/TDF 3 monthly for HBV DNAIf PCR positive in 6 months,start combination therapy

Acute failure Positive - ETV/LdT/TDF 3 monthly for resistance

If resistance, add second drug

Acute failure Negative Positive LdT/ETV/TDF 3 monthly for HBV DNA

If resistance, add second drug

Acute failure Negative Negative If transplant candidate, start antiviral

Notes:

HBeAg positive:- Low viral load for LAM is


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