update on hepatitis managemnt and recent guidelines

1. HEPATITIS B DIAGNOSIS AND
MANAGEMENT
CHAIRPERSON : DR.P.CHANDRASEKHARA
PROFESSOR OF MEDICINE
MVJ MC & RH
PRESENTER : DR.AMAR PATIL

2. Hepatitis B
oHepatitis B is an infectious disease caused by the Hepatitis
B virus (HBV).
oIt is a major public health problem, causing chronic
hepatitis, cirrhosis of liver and hepatocellular carcinoma.
oAround 350 million people are infected worldwide (0.3%),
75% of which are Asians.
oHuman carcinogen—cause of up to 80% of hepatocellular
carcinomas.

3. History
oThe virus was not discovered until 1965 when Baruch
Blumberg, discovered the Australia antigen ( later known to
be Heptitis B Surface antigen, or HBsAg ) in the blood of
Australian aboriginal people.
oD.S.Dane and others discovered the virus particle in 1970
by electron microscopy.
oBy early 1980s the genome of the virus has been
sequenced, and the first vaccines were being tested.

5. Hepatitis B Virus
o Hepatitis B virus is a member of the Hepadnavirus Family.
o The virus particle, called Dane particle (virion), consists of an
outer lipid envelope and anicosahedral nucleocapsid core
composed of protein which encloses the viral DNA and a DNA
polymerase that has reverse transcriptase activity similar to
retroviruses.
o The envelope protein expressed on the outer surface of the
virion and on the smaller spherical and tubular structures is
referred to as hepatitis B surface antigen (HBsAg).

8. Worldwide prevalence hepatitis B
(Source:CDCHealthinformationforinternationaltravel2014http://wwwnc.cdc.gov/travel/content/yellowbook/2014/map_3-04.pdf)

9. Transmission
1. Percutaneous – Exposure to infectious blood or body
fluids ( 50 – 100 times more infectious than HIV )
2. Perinatal - Without intervention, a mother who is positive
for HBsAg has a 20% risk of passing the infection to her
offspring at the time of birth. This risk is as high as 90% if
the mother is also positive for HBeAg.
3. Sexual
4. Breast feeding after proper immunoprophylaxis does not
appear to contribute to (MTCT) transmission of HBV.

10. Concentration of HBV in Various Body
Fluids
HIGH MODERATE LOW
Blood Semen Urine, Faeces
Serum Vaginal fluid Sweat, Tears
Wound Exudates Saliva Breast Milk

11. Acute Illness - Clinical Features
oIncubation Period : Ranges from 30 days to 180 days.
oAcute Illness : Usually mild and may not be clinically
apparent, with severe or fulminant hepatitis seen only in 0.1
to 1% of cases.
oSymptoms include Fever, Fatigue, Anorexia and Jaundice.
oIn 5-10%, a serum sickness-like syndrome with arthralgias,
rash, angioedema, and, rarely proteinuria and hematuria
may develop in the prodromal phase.

12. Acute Illness – Clinical Phases
oPhase 1 (viral replication phase) – Patients are
asymptomatic during this phase; laboratory studies
demonstrate serologic and enzyme markers of hepatitis.
oPhase 2 (prodromal phase) – Patients may experience
fever, anorexia, nausea, vomiting, alterations in taste,
arthralgias, malaise, fatigue, urticaria, and pruritus.

13. oPhase 3 (icteric phase) – Patients may note dark urine,
followed by pale-colored stools; in addition to the
predominant gastrointestinal (GI) symptoms and malaise,
patients become icteric and may develop right upper
quadrant pain with hepatomegaly.
oPhase 4 (convalescent phase) – Symptoms and icterus
resolve, and liver enzymes return to normal

14. Complications and Sequelae
oThe most feared complication of Hepatitis B is fulminant
hepatitis (massive hepatic necrosis), fortunately this is a
rare event.
oPatients usually present with signs and symptoms of
encephalopathy that may evolve to deep coma.
oThere is onset of encephalopathy usually within 8 weeks
of onset of symptoms.
oThe liver is usually small and the PT excessively prolonged.

15. Hepatic Failure with Encephalopathy
Rapidly
shrinking liver
size
Rapidly rising
bilirubin level
Marked
Prolongation
of PT
Clinical signs of
Confusion,
Disorientation

16. Chronic Hepatitis B – Clinical Features
oProgression to chronicity is as high as 95% in neonates
compared to only 1-5% in adults.
oPersistence of Anorexia, Weight loss and Fatigue may be
suggestive of progression.
oPhysical findings may include Persistent Hepatomegaly.
oMost cases of chronic hepatitis B among adults, however,
occur in patients who never had a recognized episode of
clinically apparent acute viral hepatitis.

17. Extrahepatic manifestations, when they
occur may include
oArthralgias
oArthritis,
oHenoch-Schonlein purpura,
oGeneralized vasculitis ( polyarteritis nodosa ),
oGlomeurulonephritis,
oPleural effusions,
oPericarditis,
oAnd aplastic anemia.

18. Uncommon complications of HBV infection include
pancreatitis, myocarditis, atypical pneumonia, transverse
myelitis, and peripheral neuropathy.

19. Natural History of the Disease
Depending upon the interaction of host immunity and viral
replication chronic Hepatitis B can be divided into five
phases, all of which are not necessarily seen in all patients
and may not always develop sequentially.
1.Immune tolerant phase
2.Immune clearance phase
3.Inactive residual phase
4.HBeAg negative hepatitis
5.HBsAg negative phase

20. Disease Phases in Chronic HBV Infection
Phase HBsAg HBeAg Anti-
HBe
ALT HBV DNA
range
Immune Tolerant + + - Normal >8 log IU/mL
Immune
Clearance
+ + - Normal or
elevated
3-8 log IU/mL
Inactive Disease + - + Normal <3 log IU/mL
HBeAg-negative
Chronic HBV
+ - + Normal or
elevated
3-8 log IU/mL

21. Acute Illness – Lab Features
oThe serum aminotransferases - aspartate
aminotransferase (AST) and alanine aminotransferase
(ALT) increase to a variable degree during the prodromal
phase of acute viral hepatitis and precede the rise in
bilirubin level.
oThe level of these enzymes, however, does not correlate
well with the degree of liver cell damage. Peak levels vary
from 400–4000 IU or more; these levels are usually reached
at the time the patient is clinically icteric and diminish
progressively during the recovery phase of acute hepatitis.

22. oThe serum bilirubin may continue to rise despite falling serum
aminotransferase levels. In most instances, the total bilirubin is
equally divided between the conjugated and unconjugated
fractions.
oNeutropenia and lymphopenia are transient followed by a
relative lymphocytosis.
oMeasurement of the prothrombin time (PT) is important in
patients with acute viral hepatitis, because a prolonged value
may reflect a severe hepatic synthetic defect, signify extensive
hepatocellular necrosis, and indicate a worse prognosis.

23. During the acute phase of viral hepatitis, antibodies to
smooth muscle and other cell constituents may be present,
and low titers of rheumatoid factor, nuclear antibody, and
heterophile antibody can also be found occasionally.

24. Chronic Illness - Lab Features
oSerum bilirubin, aspartate transaminase and
gammaglobulin are only moderately increased.
oSerum albumin is usually normal.
oAt time of presentation, features of hepato-cellular disease
are usually mild.

25. Lab Features - Serological Markers
Virus-specific antibodies, which appear during and after
hepatitis virus infection, are serologic markers of diagnostic
importance.

26. HBsAg
oHBsAg appears in the blood about 6 weeks after infection
and has usually disappeared by 3 months after the clinical
illness. Persistence for more than 6 months implies the
development of a carrier state or progression to chronicity.
oA diagnosis of HBV infection can usually be made by
detection of HBsAg in serum.
oRarely, levels of HBsAg are too low to be detected during
acute HBV infection, even with contemporary, highly
sensitive immunoassays.

27. HBsAg and Degree of Liver Damage
oAn inverse correlation exists between the serum
concentration of HBsAg and the degree of liver cell
damage. For example, titers are highest in
immunosuppressed patients, lower in patients with chronic
liver disease, and very low in patients with acute fulminant
hepatitis.
oThese observations suggest that, in hepatitis B, the degree
of liver cell damage and the clinical course are related to
variations in the patient’s immune response to HBV rather
than to the amount of circulating HBsAg.

28. HBsAg – Quantitative Assay
oHBsAg (Quantitative) assay is a diagnostic test for assessing the
amount of the Hepatitis B surface antigen (HBsAg) in chronic
Hepatitis B patients.
oThe quantitative electrochemiluminescence immunoassay
determines the HBsAg levels expressed in IU/mL (or) s/c and is
widely used to monitor chronic Hepatitis B (CHB) patients response
to antiviral Therapy.
oInterpretation : HBsAg < 1 s/c = Negative
HBsAg 1-5 s/c = Intermediate
HBsAg > 5 s/c = Positive

29. Anti - HBc (Antibody to HBV core antigen):
oTotal - indicates past or active infection; whether
person is immune or chronic carrier
oSpecificity = 99.8% to 99.9%
oIgM - early indicator of acute infection
oNo antigen test

30. o In patients with hepatitis B surface antigenemia of
unknown duration testing for IgM anti-HBc may be
useful to distinguish between acute or recent infection
(IgM anti-HBc-positive) and chronic HBV infection (IgM
anti- HBc-negative, IgG anti-HBc-positive).
o A false-positive test for IgM anti-HBc may be encountered
in patients with high-titer rheumatoid factor.

31. HBeAg
oHBeAg correlates with ongoing viral synthesis and with
infectivity. It is transiently present during the acute attack.
It is present for a shorter time than HBsAg.
oPersistence for more than 10 weeks strongly suggests the
development of chronicity.
oIts principal clinical usefulness is as an indicator of relative
infectivity.
oSelecting patients for therapy.

32. Anti-HBe (Antibody to HBVe Antigen)
o Prognostic for resolution of infection
o Less infectious
o Spontaneous seroconversion in 10 to 20% of healthy
adults per year.
oThe appearance of Anti-Hbe is strong evidence that the
patient will recover completely.

33. Anti HBs
oAnti-HBs is rarely detectable in the presence of HBsAg in
patients with acute hepatitis B, but 10–20% of persons with
chronic HBV infection may harbor low-level anti-HBs.
oAfter immunization with hepatitis B vaccine, which
consists of HBsAg alone, anti-HBs is the only serologic
marker to appear.
oAnti-HBs >12mIu – Protective.

34. Molecular Advances in Diagnosis of HBV
Infection
oCurrent HBV DNA assays make use of differing
technologies and can generally divided into i) signal
amplification assays ii) DNA amplification tests based on
the Polymerase chain reaction (PCR)
oHBV DNA detection based on PCR approach can detect as
few as 10 2 – 10 3 Genome copies.
oThese markers are useful in following the course of HBV
replication in patients with chronic hepatitis B receiving
antiviral chemotherapy

35. HBV DNA
oHBV DNA is the most sensitive index of viral replication.
oIt is a good marker of the level of viraemia, can be
correlated with serum transaminase levels and parallels the
presence of HBsAg in serum.
oPatients with an HBV pre-core mutant are HBeAg negative
and HBV DNA positive.

36. Needle Liver Biopsy
oLiver biopsy has been used to ascertain the degree of
necroinflammation and fibrosis, and to help guide the
decision to treat.
oHepatic histology varies widely and includes chronic
hepatitis, active cirrhosis and hepato-cellular carcinoma.
oThe amount of replicating virus in the serum does not
correlate with the degree of histological activity

38. Non-Invasive Tests (NITs)
oNon-invasive methods for assessing the stage of liver
disease are supplanting liver biopsy and have been validated
in adults with CHB.
oBlood and serum markers for fibrosis, including APRI and
FIB-4, or transient elastography (FibroScan) performed to
rule out advanced fibrosis.

39. APRI & FIB-4
oSeveral studies have proven that APRI and FIB-4 are good
predictors of the Stage of Liver Fibrosis in Chronic Hepatitis B.
oBoth APRI and FIB-4 could be considered as supplemental
parameters by which to differentiate significant fibrosis from
none to minimal fibrosis.
oAlthough the diagnostic accuracy of APRI and FIB-4 is slightly
lower than biopsy, these tools remain attractive for estimating
liver fibrosis in resource-limited areas where the burden of
chronic hepatitis B is very high.

40. APRI
AST to Platelet ratio index
oIn a meta-analysis of 40 studies, investigators concluded that an
APRI score greater than 1.0 had a sensitivity of 76% and specificity
of 72% for predicting cirrhosis. In addition, they concluded that APRI
score greater than 0.7 had a sensitivity of 77% and specificity of 72%
for predicting significant hepatic fibrosis.

41. FIB-4
The Fibrosis-4 score helps to estimate the amount of scarring in the liver.

42. FIB-4 Interpretation
oUsing a lower cutoff value of 1.45, a FIB-4 score <1.45 had
a negative predictive value of 90% for advanced fibrosis.
oIn contrast, a FIB-4 >3.25 would have a 97% specificity and
a positive predictive value of 65% for advanced fibrosis.
oIn the patient cohort in which this formula was first
validated, at least 70% patients had values <1.45 or >3.25.
oHence it was concluded that these individuals could
potentially have avoided liver biopsy with an overall
accuracy of 86%.

43. Fibroscan
oMore recently, new techniques that measure liver stiffness
have been developed based on ultrasound technology.
oTransient elastography performed with FibroScan has
been the most widely evaluated.
o>90% accuracy for early Fibrosis and Cirrhosis.
oCost in India – Rs.4000 to 5000/- per scan.

46. Commonly Encountered
Serological Patterns of Hepatitis B
Infection

47. HBsAg Anti-HBs Anti-HBc HBeAg Anti-Hbe Interpretation
+ - IgM + - Acute Hepatitis B – High Infectivity
+ - IgG + - Chronic Hepatitis B – High Infectivity
+ - IgG - + 1. Late acute or chronic hepatitis B, low
infectivity
2. HBeAg-negative (“precore-mutant”)
hepatitis B (chronic or, rarely, acute)
- - IgM +/- +/- 1. Acute hepatitis Ba
2. Anti-HBc “window”
- - IgG - +/- 1. Low-level hepatitis B carrier
2. Hepatitis B in remote past
- + IgG - +/- Recovery from Hepatitis B
- + - - - 1. Immunization with HBsAg (after
vaccination)
2. Hepatitis B in the remote past (?)
3. False-positive

50. PREVENTION & IMMUNOPROPHYLAXIS
Hepatitis B immunoglobulin (HBIG) :
oIt is effective for passive immunization if given
prophylactically or within hours of infection.
oHepatitis vaccine should always be given with HBIG,
particularly if the subject is at risk of re-infection.
o It is indicated for sexual contacts of acute sufferers, babies
born to HBsAg-positive mothers and victims of parenteral
exposure (needle stick) to HBsAg-positive blood.

51. HBV Vaccine
oIn healthy individuals the recombinant vaccine is given in a
dose of 20μg (2 ml) intramuscularly, repeated at 1 month
with a booster at 6 months.
oThis induces sufficient antibody response in at least 94% of
individuals.
oIt is given intramuscularly into the arm.
oFor patients undergoing haemodialysis and for other
immunosuppressed patients, higher vaccine dosages (40μg)
or an increased number of doses are recommended
(4 doses).

52. HBV Vaccine - Indications
1. Health care workers including medical students.
2. Mental subnormality.
3. Accidental exposure to HBsAg-positive blood.
4. Close family and sexual contacts of HBsAg-positive carriers.
5. Babies born to HBsAg-positive mothers.
6. Children as part of ‘Expanded Program on Immunization’ (EPI).
7. Drug abusers.
8. Homosexually active men.
9. Travellers to high-risk areas.

53. Prophylaxis of persons accidentally
exposed to possibly infectious blood
Give at once – 0.06ml/Kg HBIG plus first dose of Hepatitis B
Vaccine and continue vaccine course.

54. Management – Acute Hepatitis B
oIn hepatitis B, among previously healthy adults who
present with clinically apparent acute hepatitis, recovery
occurs in ~99%; therefore, antiviral therapy is not required.
oIn rare instances of severe acute hepatitis B, institution of
antiviral therapy with a nucleoside analogue (entecavir or
tenofovir, the most potent and least resistance-prone
agents) should continue until 3 months after HBsAg
seroconversion or 6 months after HBeAg seroconversion.

55. Management of Fulminant Hepatitis
oBy maintenance of fluid balance, support of circulation and
respiration, control of bleeding, correction of hypoglycemia, and
treatment of other complications of the comatose state in
anticipation of liver regeneration and repair.
oProtein intake should be restricted.
oOral lactulose or neomycin administered.
oMeticulous intensive care that includes prophylactic antibiotic
coverage is the one factor that does appear to improve survival.
oOrthotopic liver transplantation is resorted to with increasing
frequency, with excellent results, in patients with fulminant
hepatitis. Disease does not recur in transplanted liver.

56. Management of CHB
oThe currently approved treatment options include
immunomodulatory therapies ( including conventional
interferon alpha IFNα, Pegylated Interferon α ) and
Nucleoside/Nucleotide Analogs (NA’s).
oThe nucleoside analogs include ( lamivudine, entecavir,
telbivudine and emtricitabine ) and nucleotide analogs
include ( adefovir and tenofovir ).

57. Who should be considered for treatment?
Immune
escape
< <> >
HBeAg+ve HBeAg–ve
ALT
HBV-DNA
Inactive (carrier)
state
HBeAg –ve/+ve active
chronic hepatitis
HBeAg +ve
chronic hepatitis
Immune
tolerance
Immune
clearance
Immune
control
treat treat

58. TREATMENT RECOMMENDATIONS
HBeAg HBV DNA ALT Treatment Strategy
POSITIVE >20,000 IU/mL ≤2 x ULN Low efficacy of treatment
If ALT < ULN observe
If ALT 1-2 x ULN :
•Consider Biopsy if age >40, family h/o
HCC
•Treat if biopsy shows substantial
inflammation or fibrosis
>20,000IU/mL >2 x ULN •Treat with any of recommended agents
•Entecavir and Tenofovir are favoured
over earlier generation drugs.
•PEG IFN has supplanted standard IFN
•Liver Biopsy optional

59. TREATMENT RECOMMENDATIONS
HBeAg HBV DNA ALT Treatment Strategy
NEGATIVE >20,000 IU/mL >2 x ULN •Treat with any of the recommended
agents
•Liver Biopsy Optional
>2000 IU/mL 1-2 x ULN •Consider Biopsy
•Treat if biopsy shows substantial
inflammation or fibrosis
<2000 IU/mL < ULN No treatment
Observe ( Inactive carrier )

60. INTERFERON ( FDA 1991 )
oIFN-α was the first approved therapy for chronic hepatitis B, no
longer used in the treatment of Hepatitis B.
oDose used was a 16-week course of IFN given subcutaneously at a
daily dose of 5 million units, or three times a week at a dose of 10
million units,
oSeroconversion from HBeAg to anti-HBe occurred in approximately
20%, and, in early trials, approximately 8% lost HBsAg.
oInitial trials of brief-duration IFN therapy in patients chronic
hepatitis B were disappointing, suppressing HBV replication
transiently during therapy but almost never resulting in sustained
antiviral responses.

61. LAMIVUDINE ( FDA 1998 )
oThe first of the nucleoside analogues to be approved, the
dideoxynucleoside lamivudine inhibits reverse transcriptase
activity of both HIV and HBV and is a potent and effective
agent for patients with chronic hepatitis B.
oDOSE – 100mg P/O Once daily.
oDURATION – Until HBeAg Conversion. Patients should
receive a period of consolidation therapy of ≥6 months in
Western patients and ≥1 year in Asian patients after HBeAg
seroconversion.

62. LAMIVUDINE – Contd
oClinical and laboratory side effects of lamivudine are negligible.
oLamivudine has been shown to be effective in the treatment of
patients with decompensated hepatitis B, in some of whom
decompensation can be reversed.
oAmong patients with cirrhosis or advanced fibrosis, lamivudine has
been shown to be effective in reducing the risk of progression to
hepatic decompensation and, marginally, the risk of HCC.
oBecause of the need for long lamivudine treatment courses, low
barrier to resistance, and efficacy inferior to that of later generation
anti-virals, lamivudine is no longer a first-line treatment for chronic
HBV.

63. ADEFOVIR (FDA 2002)
oIt is an orally administered nucleotide analog reverse
transcriptase inhibitor (ntRTI).
oDOSE – 10mg P/O Once daily.
oA 48-week course of adefovir dipivoxil was shown to
achieve histologic improvement (and reduce the
progression of fibrosis) and normalization of ALT in just over
one-half of patients, HBeAg seroconversion in 12%, HBeAg
loss in 23%, and suppression to an undetectable level of
HBV DNA in 13−21%, as measured by PCR.

64. ADEFOVIR – Contd
oThe therapeutic effect is lost once the drug is stopped.
Continued treatment is required to maintain the anti-viral
response.
oAmong patients co-infected with HBV and HIV and who
have normal CD4+ T cell counts, adefovir dipivoxil is
effective in suppressing HBV dramatically.

65. Adefovir – In Lamivudine Resistance
oAdefovir dipivoxil is effective in lamivudine-resistant,
YMDD-mutant HBV and can be used when such lamivudine-
induced variants emerge.
oWhen lamivudine resistance occurs, adding adefovir (i.e.,
maintaining lamivudine to preempt the emergence of
adefovir resistance) is superior to switching to adefovir.

66. Adefovir – Adverse Effects
oAdefovir was found to be nephrotoxic at high doses (60-
120mg).
oEven at 30 mg/d, creatinine elevations of 0.5 mg/dL
occurred in 10% of patients; however, at the HBV-effective
dose of 10 mg, such elevations of creatinine are rarely
encountered. However creatinine monitoring is advised
during treatment.

67. PEGYLATED INTERFERON (FDA 2005)
oPEG INTERFERON α2a is the only Interferon approved for
the treatment of Chronic Hepatitis B
oDOSE - 180μg SC weekly * 48 weeks.
oCost – Rs.15,000 per dose. Almost 7.5 – 8 lac rupees for a
full course.

68. ENTECAVIR (FDA 2005)
oEntecavir, an oral cyclopentyl guanosine analogue
polymerase inhibitor, appears to be the most potent of the
HBV antivirals and is well tolerated.
oEntecavir is also effective against lamivudine-resistant HBV
infection.
oDOSE – 0.5 – 1mg daily.
oEntecavir has an excellent clinical profile.

69. TELBIVUDINE ( FDA 2006 )
oTelbivudine, a cytosine analogue, is similar in efficacy to
entecavir but slightly less potent in suppressing HBV DNA.
oSIDE EFFECTS – Creatinine Kinase elevations, Peripheral
Neuropathy, Lactic Acidosis.
oTelbivudine is neither recommended as first-line therapy
nor widely used.
oCost – Rs.90 to Rs.200 per tablet

70. TENOFOVIR ( FDA 2008 )
oTenofovir disoproxil fumarate, an acyclic nucleotide analogue
and potent antiretroviral agent used to treat HIV infection, is
similar to adefovir but more potent in suppressing HBV DNA and
inducing HBeAg responses.
oDOSE – 300mg once daily ( Cost – Rs.45/- per tablet )
oTenofovir has supplanted adefovir both as first-line therapy for
chronic hepatitis B and as add-on therapy for lamivudine
resistant chronic hepatitis B.
oFrequency of tenofovir administration should be reduced in
patients with impaired creatinine clearance.

71. Newer Anti-virals - Emtricitabine
oEmtricitabine, a fluorinated cytosine analogue very similar
to lamivudine in structure, efficacy, and resistance profile,
offers no advantage over lamivudine.
oA combination of emtricitabine and tenofovir is approved
for the treatment of HIV infection and is an appealing
combination therapy for hepatitis B, especially for
lamivudine-resistant disease; however, neither
emtricitabine nor the combination is approved yet for
hepatitis B ( Emtricitabine 200mg ; Tenofovir 245mg )

72. Combination Therapy
oCombinations of oral nucleoside/nucleotide agents have
not achieved an enhancement in virologic, serologic, or
biochemical efficacy over that achieved by the more potent
of the combined drugs given individually
oEmphasis in the development of antiviral therapy for
Hepatitis B was placed on monotherapy; whether
combination regimens will yield additive or synergistic
efficacy is yet to be determined.

73. SECOND-LINE ANTIVIRAL THERAPIES FOR
MANAGEMENT OF TREATMENT FAILURE
In persons with confirmed or suspected antiviral resistance to
lamivudine, entecavir, adefovir or telbivudine, a switch to
tenofovir is recommended.
Treatment failure :
o Failure of an antiviral drug to reduce HBV DNA levels by ≥1 x
log10IU/mL within 3 months.
o Rebound of HBV DNA levels of ≥1 x log 10IU/mL from the
nadir in persons with an initial antiviral treatment effect.

74. Efficacy of Antiviral therapy in CHB
( Ref. CMDT 2015 )
HBeAg POSITIVE
DISEASE
PEGYLATED
INTERFERON
α2a
LAMIVUDINE TELBIVUDINE ENTECAVIR ADEFOVIR TENOFOVIR
HBV DNA loss at 1
year
25% 40-44% 60% 67% 21% 76%
HBe Seroconversion
at 1 year
27% 16-21% 22% 21% 12% 21%
HBsAg loss at 1 year 3% 1% 0% 2% 0% 3.2%
ALT Normalization at
1 year
39% 41-75% 77% 68% 48% 68%

75. Efficacy of Antiviral therapy in CHB
HBeAg NEGATIVE
DISEASE
PEGYLATED
INTERFERON
α2a
LAMIVUDINE TELBIVUDINE ENTECAVIR ADEFOVIR TENOFOVIR
HBV DNA loss at 1
year
63% 60-73% 88% 90% 51% 93%
HBsAg loss at 1 year 4% 0% 0% 0% 0% 0%
ALT normalisation
at 1 year
38% 60-79% 74% 78% 72% 76%

76. When to Stop Treatment ?
Lifelong NA therapy : All persons with clinical evidence of
Cirrhosis.
Discontinuation and careful long term follow up in :
oPersons without clinical evidence of cirrhosis
oEvidence of HBeAg loss and seroconversion to anti-HBe
after completion of atleast 1 year of treatment.
oIn association with persistently normal ALT levels and
persistently undetectable HBV DNA levels

77. Inactive Carriers
The inactive HBsAg carrier state is diagnosed by absence of
HBeAg and presence of anti-HBe, undetectable or low
levels of HBV DNA in PCR-based assays, repeatedly normal
ALT levels, and minimal or no necroinflammation, slight
fibrosis, or even normal histology on biopsy.
Advice : Regular monitoring of ALT, avoid use of alcohol
and protected sexual intercourse.

78. Special Groups : HBV-HIV coinfection
oGenerally, for HBV-HIV co-infected patients who do not yet
meet treatment criteria for HIV infection, treating for both
HBV and HIV is recommended.
oLamivudine, Emtricitabine and Tenofovir are all nucleoside
analogs with activity against both HIV and HBV.
oRate of HBV resistance to Lamivudine in HBV-HIV
coinfection is almost 90% at 4 years, hence lamivudine
should never be used as monotherapy.

79. oAdefovir has been used successfully to treat chronic
hepatitis B in HBV-HIV co-infected patients but is no longer
considered a first-line agent for HBV.
oEntecavir has low-level activity against HIV and can result
in selection of HIV resistance; therefore, it should be
avoided in HBV-HIV co-infection.
oTenofovir and the combination of tenofovir and
emtricitabine in one pill are approved therapies for HIV
and represent excellent choices for treating HBV infection
in HBV-HIV co-infected patients.

80. HBV-HCV Co-Infection
Often these patients have relatively non replicative chronic
hepatitis B infection.
oWhen both viruses need to be treated, PEG IFN α ( with
ribavarin for hepatitis C ) can be used to address both
infections.
oAlternatively both diseases can be treated independently
with PEG IFN-α plus ribavarin for hepatitis C and one of the
oral agents for hepatitis B.

81. CHB on Cytotoxic Chemotherapy
oPatients with chronic hepatitis B who undergo cytotoxic
chemotherapy for treatment of malignancies experience
enhanced HBV replication and viral expression on
hepatocyte membranes during chemotherapy coupled with
suppression of cellular immunity. Such patients are at risk
of reactivation of Hepatitis B.
oPreemptive treatment with anti-virals for 6 months for
inactive Hepatitis B carriers prior to the initiation of
chemotherapy has been shown to reduce the risk of such
reactivation.

82. Liver Transplantation
oLiver transplantation is currently a successful therapy for
end-stage chronic HBV-associated liver disease.
oUntil early 1990s, transplantation resulted in an 80% rate
of re-infection in the absence of prophylaxis.
oThe use of high dose HBIG ( Hepatitis B immunoglobulin )
peri-operatively and post-operatively, combined with
treatment of heptitis B with entecavir or tenofovir are
favored to prevent recurrent HBV infection post-
transplantation.

83. Screening for HCC
oPatients who are HBsAg positive with chronic hepatitis or
cirrhosis, especially if male and more than 45 years old,
should be screened regularly so that hepato-cellular
carcinoma may be diagnosed early when surgical resection
may prove possible.
oSerum α-fetoprotein should be measured and ultrasound
examination performed at 6-monthly intervals.

84. References
oHarrison’s Internal Medicine Volume 1 – 19 th Edition.
oWiley : Sheila Sherlock’s Diseases of the Liver and Biliary System 12th
Edition
oCurrent Diagnosis and Treatment in Gastroenterology 2nd Edition
oAPI Textbook of Medicine 10th Edition
oMedicine Updates by API – 2016 Edition
oGastroenterology for Physicians by Asian Insititute of Gastroenterology.
oWHO’s Guidelines for the prevention, care and treatment of persons
with chronic hepatitis B infection.
oCMDT 2015

85. THANK YOU