TREATMENT OF

HEPATITIS B VIRUS
• INFECTION
Yulia Dewi Pratiwi

• 1610211122

• FK UPN VETERAN JAKARTA

The most common efficacy end points in clinical trials of hepatitis B virus infection are
seroconversion from HBeAg from positive to negative and suppression of HBV DNA
to undetectable levels. These end points are correlated with improvement in
necroinflammatory disease, a decreased risk of hepatocellular carcinoma and
cirrhosis, and a decreased need for liver transplantation.

As of 2006 there were three oral nucleoside/nucleotide analogs and two injectable interferon
drugs available in the United States for the treatment of chronic HBV infection. Although
three of the current antiretroviral NRTIs (emtricitabine, lamivudine, and tenofovir) have
potent activity against HBV, only lamivudine is approved for clinical treatment.
Although not FDA-approved, tenofovir is recommended by recent consensus
guidelines for the treatment of patients co-infected with HBV and HIV-1. The anti-
herpes agent famciclovir also has anti-HBV activity, but it is relatively weak and
requires thrice-daily dosing.
Because NRTI agents may be used in patients co-infected with hepatitis B and HIV,
it is important to note that acute exacerbation of hepatitis may occur upon
discontinuation or interruption of these agents.
 LAMIVUDINE
• Lamivudine inhibits HBV DNA polymerase and HIV reverse transcriptase by
competing with deoxycytidine triphosphate for incorporation into the
viral DNA, resulting in chain termination.

• Lamivudine achieves 3-4 log decreases in viral replication in most patients and
suppression of HBV DNA to undetectable levels in about 44% of patients.

• In the doses used for HBV infection, lamivudine has an excellent safety profile.

• Headache, nausea, and dizziness are rare.

• Co-infection with HIV may increase the risk of pancreatitis.

• No evidence of mitochondrial toxicity has been reported.

ADEFOVIR DIPIVOXIL
• Although initially and abortively developed for treatment of HIV infection, adefovir
dipivoxil gained approval, at lower and less toxic doses, for treatment of HBV infection.

• Menghambat DNA polymerase dengan berkompetisi langsung dengan substrat

endogen deoksiadenosin trifosfat —> integrasi dengan HBV-DNA —> pembentukan
DNA terhenti.

• Adefovir dipivoxil is well tolerated. A dose-dependent nephrotoxicity has been observed in

clinical trials, manifested by increased serum creatinine with decreased serum
phosphorous and more common in patients with baseline renal insufficiency.

• Other potential adverse effects are headache, diarrhea, asthenia, and abdominal pain. As
with other NRTI agents, lactic acidosis and hepatic steatosis are considered a risk owing to
mitochondrial dysfunction.

• Adefovir is embryotoxic in rats.

 ENTECAVIR
• Entecavir is an orally administered guanosine nucleoside analog that competitively
inhibits all three functions of HBV DNA polymerase, including base priming, reverse
transcription of the negative strand, and synthesis of the positive strand of
HBV DNA.

• Oral bioavailability approaches 100% but is decreased by food; therefore,

entecavir should be taken on an empty stomach.

• It is excreted by the kidney, undergoing both glomerular filtration and net tubular
secretion.

• Entecavir is well tolerated. The most frequently reported adverse events are
headache, fatigue, dizziness, and nausea.

• Lung adenomas and carcinomas in mice, hepatic adenomas and carcinomas in rats and
mice, vascular tumors in mice, and brain gliomas and skin fibromas in rats have been
observed at varying exposures.

• Co-administration of entecavir with drugs that reduce renal function or compete for
active tubular secretion may increase serum concentrations of either entecavir or the
co-administered drug.
 INTERFERON ALPHA
KONVENSIONAL
• Antivirus: menghambat replikasi virus
secara langsung melalui aktivasi endo-
ribonuclease, elevasi protein kinase dan
induksi 2’,5’-olygodenylate synthase.

• Antiproliferasi

• Imunomodulator: mengaktivasi makrofag, sel

NK, dan limfosit T sitotoksik serta
memodulasi pembentukan antibodi yang
akan meningkatkan respon imun host
PEGYLATED INTERFERON
ALPHA-2A
• Imunomodulator: mengaktivasi makrofag,
sel NK, dan limfosit T sitotoksik serta
memodulasi pembentukan antibodi yang
akan meningkatkan respon imun host

• Anti-virus: menghambat replikasi virus

secara langsung melalui aktivasi endo-
ribonuclease, elevasi protein kinase dan
induksi 2’,5’-olygodenylate synthase.
 THYMOSIN ALPHA-1

• Masih diperlukan penelitian lebih lanjut.

• Imunomodulator: mengaktivasi makrofag,

sel NK, dan limfosit T sitotoksik serta
memodulasi pembentukan antibodi yang
akan meningkatkan respon imun host