Update Management of Hepatitis B Infection

INTRODUCTION
• Hepatitis is an inflammation of the liver that is caused by a
variety of infectious viruses and noninfectious agents
leading to a range of health problems, some of which can
be fatal.
• Hepatitis B can lead to chronic disease in hundreds of
millions of people => the most common cause of liver
cirrhosis, liver cancer and viral hepatitis-related deaths.
• An estimated 354 million people worldwide live with
hepatitis B, and for most, testing and treatment remain
beyond reach.
2
Global Disease Burden
• 296 million [228–423 million] people living with chronic
hepatitis B virus infection
• 6 million [4–11 million] children younger than five living with
hepatitis B virus infection => South East Asia
• Viral hepatitis was the 9th ranked cause of human death; similar
numbers of deaths to HIV, malaria and TB (GBD 2010)
‒ Lozano, R et al 2012. Lancet;380:2095-128. Cowie, B et al 2013. Antiviral Ther;18:953-954.

• Liver cancer is the 2nd most common cause of cancer death

globally
‒ GBD report 2013
3
Hepatitis B
• The virus is most commonly transmitted from mother to
child during birth and delivery, as well as through contact
with blood or other body fluids during sex with an infected
partner, unsafe injections or exposures to sharp instruments.
• In 2019, hepatitis B resulted in an estimated 820 000 deaths,
mostly from cirrhosis and hepatocellular carcinoma (primary
liver cancer).
• Hepatitis B can be prevented by vaccines that are safe,
available and effective
4
Hepatitis B in pregnancy

5|
 Manifestasi hepatitis B

Compensated
Resolution Stabilisation cirrhosis

Acute Chronic
hepatitis Cirrhosis Liver cancer
infection
Death

Chronic Carrier Progression Decompensated

Cirrhosis
(Death)

10–20 years
 Course of HBV is Determined by the Acquisition Time

80% Inapparent disease

90-99% Recovery
Childhood and Adult
20% Acute Hepatitis
1-12% become chronic
1% Fulminant Hepatitis
1-12% Per year Very low risk

HBV Infection Cirrhosis HCC

1-12% Per year 0.5% Per Year

Neonatal Inapparent Disease 95% become Chronic

 Komplikasi Hepatitis B pada Kehamilan

Semakin muda usia saat terinfeksi, maka semakin tinggi

risiko Hepatitis B kronik

World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. 2015.
 Indonesia has moved from high to
intermediate endemicity of hepatitis B

Parameter 2007 2013

1-14 >15 Total 1-14 >15 Total
years years years years
HBsAg (+) 8.3% 9.6% 9.4% 4.7% 6.6% 7.1% 18 million people
Anti-HBc (+) 10.9% 34.7% 32.8% 4.3% 31.8% 31.9%
Anti-HBs (+) 32.2% 28.8% 30.6% 32.6% 35.5% 35.6%
 Phases of disease in chronic hepatitis B
Pattern of Geographical areaPercent of Predominant age at Predominant
prevalence population infection mode of
HBsAg positive transmission
High ≥ 8% Southeast Asia, 8%-20% Perinatal and early Maternal-infant,
China, Pacific childhood percutaneous
Islands, (e.g.,
Sub- Saharan unsterile medical
Africa equipment used
in vac-
cination,
traditional
medicine
practices)
Intermediate Eastern Europe, 2%-7% Early Percutaneous
the childhood/adolesce (e.g., horizontal
Mediterranean nce transmis-
2%-7% basin, Middle sion between
East, Central and children through
open
Croagh CM, Lubel JS. Natural history of chronic hepatitis B: phases in a complex relationship. World J Gastroenterol.
2014;20(30):10395-404.
 Distribution of HBsAg (+) according to Age Group

Program Nasional Vaksinasi

Hepatitis sejak 1997

Riskesdas 2013
Prevalensi HBsAg pada
kelompok usia 5 tahun: 4.2%

The United Nations:

Most of the burden of disease from HBV infection comes from infections
acquired before the age of 5 years
incidence of chronic HBV infection at 5 years of age is an indicator of the
Sustainable Development Goal target for “combating hepatitis”.
 Perjalanan Alamiah Hepatitis B Kronik

MchMahon BJ. Natural history of chronic hepatitis B-clinical implications. Medscape J Med. 2008;10(4):91
 Phases of disease in chronic hepatitis B
Phase 1 Phase 2 Phase 3 Phase 4
Immune tolerance Immune clearance Immune control Immune escape
HBeAg positive HBeAg positive HBeAg negative HBeAg negative
Serology
HBeAb negative HBeAb negative HBeAb positive HBeAb positive
Persistently normal Persistently or Persistently normal Persistently or
ALT (IU/mL) intermittently abnormal intermittently abnormal
HBV DNA Very high (usually > High but less so than in < 2000 IU/mL (but up > 2000 IU/mL
(IU/mL) 2 × 106-2 × 107) Immune tolerant phase to 20000 IU/mL) (fluctuating)
Liver Normal or mild Moderate or severe Normal or mild Moderate to severe
hepatitis necroinflammation and inflammation inflammation and fibrosis
histology fibrosis ± cirrhosis
Age usually young Intermittent flares or May have serum Predominance of HBV
Specific (< 20-30 yr). Phase ongoing mild elevation HBsAg levels < 1000 with precore/basal core
features absent or very of ALT. Ends with IU/mL promotor mutations
short in seroconversion to
Mediterranean CHB HBeAb positive state
Immunotolerant HBeAg positive immune Inactive HBsAg carrier HBeAg negative CHB
Alternative active (AASLD)/immune state (EASL and (EASL)/ reactivation or
nomencla- reactive HBeAg positive AASLD)/residual or relapse (APASL)
ture phase (EASL) inactive chronic HBV
infection (APASL)

Croagh CM, Lubel JS. Natural history of chronic hepatitis B: phases in a complex relationship. World J Gastroenterol.
2014;20(30):10395-404.
 Virus Hepatitis B
Aktif bereplikasi

Anti HBe
tidak aktif
bereplikasi

Imunitas karena vaksinasi

atau
infeksi lampau/pernah
imunitas natural
terpapar

Anti HBc

IgM
Anti HBs

Infeksi sedang berlangsung

Dienstag JL. Hepatitis B Virus Infection. N Engl J Med. 2008;359:1486-500
 Guidelines: HBV Infection and Pregnancy

• All pregnant women should be screened

for HBV1
• Risk of chronic HBV infection linked to age
of exposure;
~90% infants, 5% adults2
• HBIG and HBV vaccine should be
administered to newborns of HBsAg-
positive mothers <12 hr after delivery1
• HBV therapy should be discussed with
expectant mothers1
• HBV flares are uncommon in pregnancy
(~9%)3
1. Terrault. Hepatology. 2018;67:1560. 2. Weinbaum. MMWR Recomm Rep. 2008;57:1.
3. Chang. Am J Gastroenterol. 2016;111:1410.
 Tata Laksana Hepatitis B dan Pencegahan
Transmisi Vertikal

Pemberian Antiviral pada Ibu Hamil Vaksin Hepatitis B dan HBIg

Proses Kelahiran
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD Guidelines for Treatment of Chronic Hepatitis B. Hepatology. 2015: 1-23.
 Immunoprofilaksis

• Vaksin Hepatitis B paling baik diberikan dalam waktu 12 jam

setelah lahir
• Hepatitis Immunoglobulin (HBIg) diberikan pada ekstremitas
yang berbeda
• Kombinasi vaksin dan Ig menurunkan risiko transmisi vertikal
dari >90% menjadi <10%

1. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD Guidelines for Treatment of Chronic Hepatitis B. Hepatology. 2015: 1-23.
2. Rekomendasi Ikatan Dokter Anak Indonesia (IDAI). Jadwal Imunisasi Anak Umur 0-18 Tahun. 2014.
 AASLD Guidance: HBV Treatment Options in
Pregnancy
Status Treatment Notes
 Preferred due to higher potency and minimized
Preferred TDF risk of emergence of viral resistance compared
with LAM or TBV

Not preferred LAM and TBV  Have been studied in pregnancy but have a low
genetic barrier to resistance
TAF  Insufficient data in pregnancy
Not recommended ETV  Category C
PegIFN  Category C

Breastfeeding is not contraindicated with antiviral therapy

TDF=tenofovir disoproxil fumarate
TAF = tenofovir alafenamide
Terrault. Hepatology. 2018;67:1560. Slide credit: clinicaloptions.com
 New Data on TAF and Prevention of MTCT in
HBV
• Retrospective analysis of TAF safety and • Prospective observational study of TAF or
efficacy in HBeAg+ pregnant women TDF in pregnant women with HBV DNA
with HBV DNA >200,000 IU/mL in China >200,000 IU/mL in China (N = 232)2
(N = 71)1 ‒ TAF (n = 116) or TDF (n = 116) initiated
‒ TAF initiated during pregnancy and during pregnancy Wk 24-35 and
continued to delivery; follow-up until Wk continued to delivery; follow-up until
24-28 Mo 6 postpartum
‒ At age 24-28 wk, all 73 infants were HBV ‒ At 7 mo of age, all 233 infants were
DNA negative and none had birth HBsAg negative, and none had birth
defects defects
‒ 86% (61/71) mothers achieved HBV DNA ‒ Comparable safety profiles for TDF and
<200,000 IU/mL at delivery TAF groups

1. Ding. Ailment Pharmacol Ther. 2020;52:1377. 2. Zeng. Clin Infect Dis. 2021;[Epub]. Slide credit: clinicaloptions.com
 Penentuan Waktu Pemberian Antiviral

Pemberian Antiviral mulai diberikan pada

usia kehamilan 28-32 minggu

Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD Guidelines for Treatment of Chronic Hepatitis B. Hepatology. 2015: 1-23.
 Penghentian Pemberian Antiviral

Antiviral dihentikan

Pregnancy 3 bulan Setiap 3- 6 bulan

Pantau fungsi hepar

Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD Guidelines for Treatment of Chronic Hepatitis B. Hepatology. 2015: 1-23.
 Per Vaginam atau Sectio Caesaria ?

Seksio caesaria tidak diindikasikan dikarenakan kurangnya data dan

mempertimbangkan risk-benefit dari SC dibandingkan pervaginam.

Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD Guidelines for Treatment of Chronic Hepatitis B. Hepatology. 2015: 1-23.
 Key Take-home Points
• All pregnant women should be screened for HBV1
• Initiation of treatment or prophylaxis per the AASLD guidance
is critical to preventing mother-to-child transmission of HBV
• TDF is the preferred treatment option among agents with
safety experience during pregnancy, based on its potency and
high genetic barrier to resistance
• TAF can now be considered as an alternative to TDF during
pregnancy
• Breastfeeding is not contraindicated with antiviral therapy
Slide credit: clinicaloptions.com
The COVID-19 pandemic jeopardizes future progress

Under a worst-case scenario, there would be a projected 5.3

million additional chronic HBV infections among children
born between 2020 and 2030 and 1 million additional HBV-
related deaths among those children later on.
“Hepatitis can’t wait”
conveying the urgency of efforts needed to eliminate hepatitis as a public health
threat by 2030. With a person dying every 30 seconds from a hepatitis related
illness – even in the current COVID-19 crisis – we can’t wait to act on viral hepatitis.