HEPATITIS B VIRUS INFECTION

“Hard to understand , Easy to treat”

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 Discovery of Hepatitis B
virus
• In 1965, Dr. Baruch S.
Blumberg at Fox Chase Cancer
Center discovered an antigen
in the blood of Australian
Aborigine and named Australia
antigen which was found to be
HBsAg
• Made the first HBV vaccine
(plasma vaccine Heptavax B),
The First “Anti-Cancer Vaccine”
• Received the Nobel Prize in
Medicine in 1976

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 Global Impact of Hepatitis B
15-40% develop cirrhosis,
liver failure or HCC

World population 350–400 million with

6 billion chronic hepatitis B
~1 million/year die from HBV-associated liver disease
WHO Fact Sheets, available at www.who.int. Accessed: September 24, 2020.
Conjeevaram, et al. J Hepatology. 2003;38:S90-S103.
Lee. N3/21/02
Engl J Med. 1997;337:1733-1745. File name 3
Lok. N Engl J Med. 2002;346:1682-1683.
 Hepatitis B Dane particle

HBsAg
HBcAg Polymerase
HBeAg
ds DNA

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 Hepatitis B Virus (HBV)

• 4 overlapping open
reading frames
• Reverse
transcriptase/ DNA
polymerase domain
overlaps with
surface gene
• 100 times more
infective than HIV
• Found in blood and
body fluids

MMWR. 2003;52:1-33.
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Ott et al. J Pediatr Health Care. 1999;13(5):211.
Ribeiro et al. Microbes and Infection. 2002;4:829.
 How do you acquire the infection?

Transfusion and Newborns of long-term

transplant recipients carriers

Individuals with multiple

Intravenous
sexual partners
drug users

Healthcare Prisoners and other

workers institutionalised people

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 New Guidelines-No Carriers

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 Assessment of HBV Patient

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 Whom to treat

HBeAg Positive HBeAg Negative

ALT < 1 x ULN ALT > 1 x ULN ALT < 1 x ULN ALT > 1 x ULN

Monitor patient HBV DNA HBV DNA HBV DNA

> 2000 IU/mL < 2000 IU/mL ≥ 2000 IU/mL

Treat if persistent Monitor patient Treat if persistent

ALT >1 x ULN ALT >1 x ULN

HBV DNA < 2000 IU/mL HBV DNA < 2000 IU/mL
Consider biopsy if persistent Consider biopsy; treat if needed
or > 30 yrs; treat if needed

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 Life Cycle of HBV

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 Point of action of Drugs

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 Treatment of Hepatitis B

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 6 End Points of HBV Cure

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 Defining HBV Cure

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 Drugs with Anti HBV Activity

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 PEG Interferon Monotherapy

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 Treatment Strategy for HBV

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 Comparison in HbeAg +ve Patient

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Comparison in HBeAg –ve Patients

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 Potent HBV DNA
suppression by NUCs

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Indication of selection of ETV or TAF
over TDF

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 NUCs Discontinuation

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 Summary

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 Conclusion

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 Acute HBV Infection
HBV
DNA

HBeAg Anti-HBe
Anti-HBe

Anti-HBs

HBsAg
Anti-HBc
IgM

0 2 4 6
Months Years
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 Chronic HBV Infection

HBV DNA

HBeAg Anti-HBe

HBsAg

Anti-HBc

Anti-HBc IgM

Months Years
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 Therapeutic endpoints over
time
Improved histology and survival

Anti-HBs+ Cure
Loss of
HBeAg to Anti-HBe HBsAg
seroconversion

HBeAg
decline
HBV DNA
suppression

= HBsAg seroconversion

TIME

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Primary Goal of Hepatitis B Therapy:
Preventing Cirrhosis, HCC, Death

Durable Suppression of
HBV Replication

Impact of viral suppression on liver disease outcomes

• Prolonged viral suppression is associated with
– Reduction in necroinflammation, fibrosis, and cirrhosis
– Reduction in decompensation
– Reduction in rates of HCC
– Reduction in mortality
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 Treatment strategies
Dual MoA Single MoA
Immunomodulatory effect Potent antiviral effect
Antiviral effect

(PEG)-IFN NAs
 
Up to 25 years follow-up Up to 7 years follow-up
Long term benefits established with both approaches

Both approaches are recommended as first-line by all

3 major international treatment guidelines

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APASL. J Hepatol 2009 EASL. J Hepatol 2009 Lok, McMahon Hepatology 2009
 What can we achieve through
therapy?

PEG-IFN NAs
 

• Sustained off-therapy • Potent antiviral response

response in ~1/3 on-therapy in ~90% of
patients after finite patients with newest
treatment course drugs

Marcellin et al. New Engl J Med 2004; Lau et al. New Engl J Med 2005;
Janssen et al. Lancet 2005; Chang et al. New Engl J Med 2006;
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Lai et al. New Engl J Med 2006; Marcellin et al. New Engl J Med 2008