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Adverse Effects of Oral Antiviral

Therapy in Chronic Hepatitis B


Kayaaslan B, Guner R

World J Hepatol 2017


INTRODUCTION
Chronic hepatitis B (CHB) one of the major cause of chronic
liver disease.
Main goal of treatment in CHB suppression of hepatitis B
virus (HBV) DNA replication.
Antiviral agents :
1. Conventional or pegylated interferons (IFN or Peg-IFN)
2. Oral nucleoside/nucleotide analogues (NAs)
Nucleoside analogues lamivudine, telbivudine, entecavir
Nucleotide analogues adefovir dipivoxil, tenofovir dipivoxil
fumarate
Class Effects of NAs
NAs suppress viral replication by the inhibition of the HBV
polymerase enzyme can cause mitochondrial toxicity.

Clinical manifestasions of mitochondrial toxicity:

Hematologic disorders

Peripheral neuropathy

Skeletal & cardiac myopathy

Pancreatitis

Hepatic failure

Lactic acidosis
Lamivudine
Dosage 100 mg/day

Class effect myopathy & neuropathy

Renal effect no significant effect

Common adverse effects upper respiratory tract


infection (URTI); headache; fatigue; CK elevation; ALT flares

Laboratory monitoring serum ALT & bilirubin

Rare severe adverse reactions rhabdomyolisis; acute


dystonia; pancreatitis; lactic acidosis
Telbivudine
Dosage 600 mg/day
Class effect myopathy & neuropathy (especially
combination with Peg-IFN)
Renal effect nephroprotective effect
Common adverse effects upper respiratory tract
infection; headache; fatigue; CK elevation (asymtomatic &
self limiting)
Laboratory monitoring CK level & serum lactate
Rare severe adverse reactions lactic acidosis
Adefovir Dipifoxil
Dosage 10 mg/day

Class effect very rare

Renal effect nephrotoxicity

Common adverse effects pharyngitis; asteni;


headache; abdominal pain; flu-like symptoms; nausea

Laboratory monitoring serum creatinine &


phosphate level

Rare severe adverse reactions hypherphosphatemia


Entecavir
Dosage 0,5-1 mg/day

Class effect very rare

Renal effect no decrease in GFR

Common adverse effects headache; URTI; fatigue;


dizziness, upper abdominal pain; nausea

Laboratory monitoring serum lactate

Rare severe adverse reactions lactic acidosis


Tenofovir
Dosage 300 mg/day
Class effect very rare
Renal effect non significant effect in decreasing
GFR; hyperphosphatemia
Common adverse effects headache;
nasopharyngitis; back pain; nausea; bone mineral
density loss
Laboratory monitoring serum creatinine; phosphate
level; BMD
Renal Safety of NAs
NAs cleared by kidney dosage should be
adjusted in creatinine clearance < 50 mL/min.

Adefovir or tenofovir should be regularly monitored


for serum creatinine & phosphate levels

Telbivudine or entecavir the recommendation


choice in patient with renal failure.
Safety in Pregnancy
Guideline in pregnancy women:

Initiation high HBV DNA level at 28-32 wk of


gestation

Cessation after delivery or 4-12 wk after delivery


who do not have a risk of ALT flares & pre-existing
advanced liver fibrosis or cirrhosis

Tenofovir or telbivudine the recommendation


choice in pregnancy
Conclusion
Treatment of CHB long-life therapy
Long-term safety factor that influence treatment
decision
All of NAs WARNING about mithocondrial
dysfunction
Further studies needed to clarify adverse effects of
NAs
Prolonged treatment experience can reveal unknown
adverse effects of NAs.
THANK YOU