1) Hepatitis B virus (HBV) infection is a global health problem affecting approximately 350-400 million people worldwide and is a leading cause of death from liver disease and cancer. 2) HBV is a DNA virus that can cause both acute and chronic infection. Chronic infection, defined as persistence of the virus for more than 6 months, puts people at risk for progressive liver disease and liver cancer. 3) Management of HBV involves antiviral therapy to suppress viral replication and prevent progression of liver disease. First line oral antiviral agents with high potency and low resistance include entecavir and tenofovir.

1. Kepaniteraan Klinik Stase Penyakit Dalam
RSIJ Sukapura
Program Studi Pendidikan Dokter
Fakultas Kedokteran dan Kesehatan
Universitas Muhammadiyah Jakarta
Tutorial
Hepatitis B
Disusun Oleh:
Zaras Yudisthira Saga
2008730133
Rikke Varianti
2008730108
Pembimbing: Dr. Iwan B. ,
Sp.PD

2. Epidemiology
• Hepatitis B virus (HBV) infection is an important global health
problem and is one of the most common chronic viral
infections.
• Approximately 350–400 million persons have chronic
infection, and more than 1 million deaths annually are due to
end-stage liver disease or hepatocellular cancer (HCC)
• HBV infection is highly prevalent in Asia, Africa, and parts of
southern and eastern Europe
• In the UK, more than 300,000 people may have chronic HBV
infection

3. Virology
• Human HBV is a member of the Hepadnaviridae family, and humans and
higher primates are the only hosts for HBV infection
• The viral genome is a 3.2-kb partially double-stranded DNA with four
overlapping reading frames
• The viral genome encodes the viral polymerase (which includes the
reverse transcriptase function), the core and surface proteins, and the
non-structural proteins (HBV e antigen [HBeAg] and X protein)
• There are eight distinct HBV genotypes, which have well-defined
geographical distribution They differ in some important respects, including
their natural history and response to interferon (IFN)-based antiviral
therapy

5. Pathogenesis and Natural
History
• The pathogenesis of liver disease in HBV infection is related to the
persistence and magnitude of viral replication.
• The course of viral infection and the severity of liver damage are
determined by the balance between viral replication and host immune
defence mechanisms
• Following acute HBV infection of adults, 95% recover spontaneously with
viral clearance not needing treatment
• Intrauterine infection and infection at a young age are strongly associated
with failure to clear the virus and with the development of chronic
infection.
• Chronic infection is defined as the persistence of HBsAg in serum for at
least 6 months after infection with hepatic inflammation

6. • Liver inflammation requires both
high levels of replication and
targeted inflammatory responses
• Chronic infection may be associated
with production and secretion by
infected hepatocytes of the HBeAg.
In that case, the level of viral
replication is almost invariably very
high
• When HBeAg negativity is
associated with high levels of
replication, the associated hepatitis
may be referred to as e-negative
hepatitis.

7. Pathogenesis and Natural
History
• Classically, four phases of chronic HBV infection have been described.
– They are the immune tolerant phase,
– The immune reactive phase,
– The inactive/resolution phase and
– The reactivation phase.

8. immune tolerant
phase
• High levels of
replication
(usually more
than 10 million
IU/mL)
• absence of
inflammatory
response
• HBeAg-positive
infection
• no cytotoxic
• T-cell reaction to
virus
immune reactive
phase
• virus is
recognized as
foreign antigen
by the immune
system
• elevated or
fluctuating ALT
• HBeAg-positivity
• moderate to
severe
inflammation on
liver biopsy
• serum HBV DNA
falls and HBeAg
secretion may
stop
inactive/resolution
phase
• inactive hepatitis
B carriers
• HBeAg-negativity
• low serum HBV (<
2,000 IU/mL)
• normal ALT
• This phase may
persist for life
with sustained
and effective
cytotoxic T-cell
responses
• 1–3% per annum
will achieve
resolution phase
with clearance of
HBsAg from
serum
reactivation phase
• Reappearance of
higher levels of
virus despite
HBeAg-negativity
• There is resumed
liver
inflammation and
progressive
fibrosis

10. Clinical Presentation and
Diagnosis
• Acute infection is characterized by arthralgia, fever, urticaria and flu-like
symptoms, followed by jaundice.
• More than 90% recover with acquired immunity;
• Fulminant hepatitis is rare, but a small proportion is persistently infected
• The majority of infection is asymptomatic, and a high proportion becomes
chronic
• Presentation in middle age with cirrhosis, which is either compensated
(features of chronic liver disease) or decompensated (ascites, hepatic
encephalopathy, and variceal bleed), is not uncommon.

11. Investigations: Viral Serology
• Those patients who present with acute hepatitis typically have
both HBsAg and immunoglobulin M (IgM) antibodies to HBV
in serum (IgM reactivity to the core antigen is typically
measured).
• Chronic HBV patients who present to clinics should be
checked for HBsAg, HBeAg and HBV DNA level.
• HBV DNA quantification is a key determinant for selection of
patients for therapy, and its measurement is necessary to
monitor response to antiviral therapy
• HBV infection can be associated with hepatitis delta virus
(HDV) infection, so HDV serology should be routinely
performed.

13. Liver Biochemistry
• Assessment of liver damage requires routine
biochemical liver function tests, including serum
albumin, and international normalized ratio
Assessment of
Fibrosis
• A liver biopsy can determine the degree of hepatic
necroinflammation (grading) and fibrosis (staging)
• serum markers and transient elastography
Monitoring Cirrhosis
and Surveillance of
HCC
• Liver ultrasound should be performed at first
assessment for all patients and every 6 months for
patients with high risk of liver cancer

14. Management
• The management of HBV has improved during recent years with the use of
IFN and with the development of safe and potent oral antiviral
nucleoside/nucleotide analogues
• The goal of therapy is to prevent the progression to cirrhosis and to
reduce risk of HCC. Antiviral efficacy is measured by the degree of HBV
• DNA suppression and rates of HBeAg and HBsAg loss, and is reflected by
improvement in liver histology.
• HBV treatment is recommended for those patients who have moderate
hepatic necroinflammation or fibrosis and high serum HBV DNA

16. • First-line therapy for the treatment-naive non-cirrhotic patient is
either IFN or an oral antiviral.
• Entecavir and tenofovir both have potent antiviral activity (90% of
treated patients have undetectable serum HBV DNA at 12 months
of therapy), good safety profiles, and very low rates of
emergence of resistance.
• Lamivudine and telbivudine should not be used as first-line
therapy because the risk of drug resistance is high.
• Adefovir has a good resistance profile, but lacks potency (50%
undetectable HBV DNA at year 1).
• In normal practice, the emergence of drug resistance is
recognized by a rise in viral load of at least 1 log10 IU/mL from
nadir titre in a compliant patient. HBV resistance can be
confirmed by genetic sequencing of the virus

17. Follow-up and HCC
Surveillance
• African or Asian ethnicity, male gender, age over 40 years,
family history of HCC, high HBV DNA titre and co-infection
with other viruses are the risk factors which are associated
with increased risk of HCC development.
• Most cancer is seen after development of cirrhosis, so
prevention of cirrhosis dramatically reduces the risk of cancer

18. HBV Infection in Special
Circumstances
Pregnancy
• Antiviral therapy for the pregnant mother
with very high titres may further reduce
the risk of transmission to the baby.
• Current recommendations suggest that
either lamivudine (Category C) or tenofovir
(Category B) can be taken by the pregnant
mother during the third trimester to
further reduce the risk of transmission to
the developing fetus and neonate.
• Breastfeeding by an HBV-positive mother
is safe, and there is a low risk of infection
(so long as the baby has been vaccinated).
Infants and Children
HBV infection is seldom associated with
significant liver damage during childhood
years. Antivirals can be used under specialist
care

19. HBV Infection in Special
Circumstances
Health-care Worker
Health-care workers who undertake
exposure-prone procedures (eg,
surgeons, obstetricians) can be given
antivirals to reduce the risk of
transmission from doctor to patient.
Co-infection
HBV and HDV co-infection is not
uncommon. Around 5% of HBV carriers
are co-infected with HDV. IFN is the
treatment of choice for HBV/HDV
infection.
In patients with HBV and HCV co-
infection, treatment is recommended to
target the dominant virus and IFN has
the advantage of being active against
both viruses.

20. Prevention: HBV Vaccination
Most countries undertake maternal
screening for HBsAg, and vaccinate the
neonate born to the HBV carrier
mother
If a person is detected with HBV
infection, family members should be
screened and vaccination should be
offered to household members and
close contacts who are HBsAg-negative

21. Liver Transplantation
• Liver transplantation is the preferred treatment for HBV-
infected individuals who present with fulminant liver failure,
decompensated liver disease and HBV-related HCC.
• Oral antiviral therapy alone or in combination with
hyperimmune immunoglobulin can prevent graft reinfection

22. Conclusion
• Currently, HBV causes nearly 1 million deaths per annum
globally. HBV vaccination will have a major impact on
prevalence of infection.
• For those with established chronic infection and evidence of
liver damage, antiviral treatment should be started early to
prevent the development of HBVrelated cirrhosis, liver failure
and liver cancer

24. Nukleosida / Nukleotida analog adalah agen antivirus oral yang menghambat
sintesis DNA HBV dengan bertindak sebagai terminator rantai DNA dan ditoleransi
dengan baik.
Dibagi menjadi 3 kelompok yaitu:
Have potent antiviral activity (90% of treated patients have
undetectable serum HBV DNA at 12 months of therapy), good
safety profiles, and very low rates of emergence of resistance.
Bukanlah terapi lini pertama karena risiko resistensi obat tinggi
Adefovir has a good resistance profile, but lacks potency (50%
undetectable HBV DNA at year 1)

25. Follow-up and HCC Surveillance
 50 % kanker hati disebabkan oleh HBV
 Etnis Afrika atau Asia, laki-laki, usia > 40 tahun, genetik HCC, meningginya titer HBV DNA dan co-
infection dengan virus lainnya.
Pregnancy
Vaksinasi dapat mencegah infeksi neonatal dalam sebagian besar kasus. Kegagalan vaksinasi
dikarenakan titer virus ibu yang sangat tinggi. Terapi antiviral dapat mengurangi risiko penularan
ke bayi. Rekomendasi obat adalah lamivudine (Kategori C) atau tenofovir (Kategori B) digunakan
pada trimester ketiga untuk mengurangi risiko penularan ke janin.
Menyusui oleh Ibu degan HBV-positif  aman, risiko rendah erjadinya infeksi (syarat bayi harus
divaksinasi).
Health-care Worker
misalnya, ahli bedah, obstetricians dapat diberikan antivirus untuk mengurangi risiko penularan.
Co-infection
Immunosuppressed Patients
Kemunculan HBV DNA pada pasien dengan Infeksi HBV sebelumnya diselesaikan atau tidak aktif
kadang-kadang diamati di immunosuppressed Serikat. cccDNA, yang berada di dalam hepatosit
terinfeksi, memainkan peran penting dalam Reaktivasi HBV selama kemoterapi kanker, selama
penggunaan beberapa Agensia hayati (terutama rituximab anti-CD20) dan berikut transplantasi
organ. Dalam keadaan ini, diindikasikan sering pro phylaxis dengan oral obat-obat antivirus.

26. Prevention
1. Vaksinasi HBV
Vaccination is the most effective way to achieve global HBV control and
to prevent cirrhosis, liver failure and liver cancer. Most countries
include HBV vaccination as part of the routine universal childhood
vaccination schedule. Universal vaccination has been shown to reduce
the incidence of HBV infection, to reduce the frequency of childhood
chronic infection, and to reduce the risk of childhood liver cancer.
2. Transplantasi hati
Liver transplantation is the preferred treatment for HBV-
infected individuals who present with fulminant liver
failure, decompensated liver disease and HBV-related HCC.