Tatalaksana Hepatitis B Kronik: Nurul Nadifa Erza 1610211084

TATALAKSANA
HEPATITIS B
KRONIK
Nurul Nadifa Erza 1610211084

Hepatitis B Virus
 Viral infection by hepatitis B virus (HBV) causes many
hepatocyte changes due to direct action of a protein
coded for by the virus HBx, HBsAg and HBcAg
 HBx decreases the mitochondrial membrane
potential and causes increased release of
ROS,dysregulation in part by binding to genomic DNA,
changing expression patterns of miRNAs, activate
transcription, and change cell expression
patterns.
 HBsAg and HBcAg, also increase ROS through
interactions with the endoplasmic reticulum.
 The increase in reactive oxygen species (ROS) after HBV
infection causes inflammation, which leads to a further
increase in ROS.ROS cause more than 20 types of
DNA damage
The life cycle of hepatitis B virus is complex. Hepatitis B is one of a few known non-retroviral viruses
which use reverse transcription as a part of its replication process.
Attachment
The virus gains entry into the cell by binding to receptors on the surface of the cell and entering it
by endocytosis mediated by either clathrin or caveolin-1.HBV initially binds to heparin sulfate
proteoglycan. The pre-S1 segment of the HBV L protein then binds tightly to the cell surface
receptor sodium taurocolate cotransporting polypeptide (NTCP), encoded by the SLC10A1gee.
NTCP is mostly found in the sinusoidal membrane of liver cells. The presence of NTCP in liver
cells correlates with the tissue specificity of HBV infection.
Penetration
Following endocytosis, the virus membrane fuses with the host cell's membrane, releasing the
nucleocapsid into the cytoplasm.
Uncoating
Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA has to be
transferred to the cell nucleus. It is thought the capsid is transported on the microtubules to the
nuclear pore. The core proteins dissociate from the partially double stranded viral DNA, which is
then made fully double stranded (by host DNA polymerases) and transformed into covalently
closed circular DNA (cccDNA) that serves as a template for transcription of four viral mRNAs.
Replication
The largest mRNA, (which is longer than the viral genome), is used to make the new copies of
the genome and to make the capsid core protein and the viral RNA-dependant-DNA-
polymerase.
Assembly
These four viral transcripts undergo additional processing and go on to form progeny virions
which are released from the cell or returned to the nucleus and re-cycled to produce even more
copies.
Release
The long mRNA is then transported back to the cytoplasm where the virion P protein synthesizes
DNA via its reverse transcriptase activity.
7 Macam Obat (Antiviral Agents)
• Prinsip Pengobatan:
 Tidak perlu terburu-buru
 Lamivudine tetapi jangan terlambat
• Tujuan Pengobatan :
 Adefovir
 Memperpanjang harapan
 Entecavir hidup (menurunkan
kebutuhan untuk
 Tenofovir tranplantasi hepar)
 Menurunkan kemungkinan
 Telbivudine
terjadinya sirosis
 Interferon alfa-2b hepatis/hepatoma
 Pegylated interferon alfa-2a

nucleoside/nucleotide
analogs
Lamivudine
 Lamivudine merupakan golongan obat antiviral
NRTI(Nucleoside & Nucleotide Reverse Transcriptase
Inhibitors) Lamivudin bekerja dengan cara
menghentikan sintesis DNA, secara kompetitif
menghambat polymerase virus(yang berfungsi untuk
replikasi dan transkripsi)
 Waktu paruh plasma ± 9 jam dan ± 70% dosis
diekskresikan dalam bentuk utuh di urin.
 Bioavailabilitas oral lamivudin adalah 80%. C-max
tercapai dalam 0.5-1.5 jam setelah pemberian dosis.
 Efek samping :
 Sakit kepala, pusing, fatigue, mulut kering dan rasa tidak
nyaman di GI.
 Peningkatan ALT dan AST dapat terjadi pada 30-40%
pasien. Biasanya peningkatan ALT dan AST berhubungan
dengan munculnya mutan HBV yang resisten terhadap
lamivudin.
Adevofir
 Competitively inhibits HBV DNA polymerase and
causes chain termination after incorporation into
viral DNA. Adefovir is active in vitro against a wide range
of DNA and RNA viruses, including HBV, HIV, and
herpesviruses.
 Oral bioavailability of adefovir is about 59%
 Adefovir is excreted by a combination of glomerular
filtration and active tubular secretion and requires
dose adjustment for renal dysfunction; however, it may be
administered to patients with decompensated liver
disease.
 Adefovir may be slower to suppress HBV DNA levels
 Other potential adverse effects are headache, diarrhea,
asthenia, and abdominal pain.
Entecavir
 Entecavir competitively inhibits all three
functions of HBV DNA polymerase, including
base priming, reverse transcription strand of
HBV DNA.
 Oral bioavailability approaches 100%
 Entecavir should be taken on an empty stomach.
 Excreted by the kidney, undergoing both
glomerular filtration and net tubular
secretion.
 Adverse effects are headache, fatigue, dizziness,
and nausea.
Telebivudine
 Telebivudine inhibits HBV DNA polymerase,
resulting in incorporation into viral DNA and
chain termination.
 HBV DNA dan HBeAg
 Adverse effects are mild; they include fatigue,
headache, abdominal pain, upper respiratory
infection, increased creatine kinase levels, and
nausea and vomiting.
Tenofovir
 Tenofovir inhibits HBV reverse transcriptase
and causes chain termination after
incorporation into DNA.
 Although similar in structure to adefovir dipivoxil,
comparative trials showed a significantly higher
rate of complete response, defined as serum
HBV DNA levels less than 400 copies/mL, as well as
of histologic improvement, in patients with chronic
HBV infection receiving tenofovir than in those
receiving adefovir dipivoxil. The emergence of
resistance appears to be substantially less
frequent during therapy with tenofovir than
with adefovir
 Adverse effect nausea, diarrhea, vomiting,
flatulence, headache, renal insufficiency
Interferon alfa-2b dan
Pegylated interferon alfa-2a
 IFN menstimulasi sistem imun melalui induksi gen
yang terlibat di dalam aktivasi sel T dan
pemrosesan antigen
 IFN berikatan dengan reseptor selular spesifik,
IFN mengaktivasi jalur transduksi sinyal JAK-
STAT, menyebabkan translokasi inti kompleks
protein seluler yang berikatan dengan interferon-
specific response element. Ekspresi aktivasi
transduksi sinyal ini adalah sintesis lebih dari dua
lusin protein yang berefek antivirus.
 Efek antivirus melalui inhibisi penetrasi virus,
inhibisi sintesis protein virus  mRNA virus,
inhibisi translasi protein virus dan inhibis
pematangan virus
Fungsi IFN
 Antivirus
 Menghambat pertumbuhan sel normal dan maligna
 Meningkatkan aktivitas sel NK
 Mempengaruhi diferensiasi sel
Efek Samping IFN
 Pada IFN- α, flu-like symptoms, fatigue, leucopenia,
dan depresi, anoreksia, rambut rontok, gangguan
mood, iritabilitas. Efek ini biasanya terjadi 6 jam
setelah diberikan obat, dan sekitar 30% pasien
mengalaminya di minggu pertama penggunaan
terapi.
 IFN juga dapat menyebabkan gangguan autoimun
(tiroiditis)
Efikasi IFN telah diperbaiki dengan
mengganti IFN standar dengan IFN
terkonjugasi polietilen glikol (PEG-IFN,
Pegylated-Interferon) yang lebih
lambat eliminasi IFN lewat ginjal
sehingga meningkatkan waktu
paruh, menyebabkan konsentrasi
plasma IFN lebih stabil, dan
penurunan frekuensi injeksi dari 3 x
menjadi 1 x seminggu.
Referensi
 Pharmacology Katzung
 https://www.ncbi.nlm.nih.gov/pubmed/12481400
 http://
www.depkes.go.id/resources/download/pusdatin/info
datin/infodatin-hepatitis.pdf
 http://
digilib.itb.ac.id/files/disk1/552/jbptitbpp-gdl-yohanes
nov-27552-2-2007ta-1.pdf
 https://www.drugbank.ca/drugs/DB00034

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Nurul Nadifa Erza 1610211084

 Pegylated interferon alfa-2a

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