Treatment of chronic hepatitis B

[Guest guest]

Gastroenterol Clin Biol. 2008 Sep 3. [Epub ahead of print]

[Treatment of chronic hepatitis B.]

[Article in French]

Asselah T, Lada O, Boyer N, ot M, Marcellin P.

Pôle des maladies de l'appareil digestif, service d'hépatologie, Inserm U773

CRB3, université Denis-Diderot-Paris-VII, hôpital Beaujon, 100, boulevard du

Général-Leclerc, 92110 Clichy, France.

In recent years, marked progress has been made in the treatment of chronic

hepatitis B. Several agents have been approved: interferon alpha-(IFN),

pegylated interferon alpha2a (PEG-IFN alpha2a), lamivudine, adefovir, entecavir,

telbivudine and recently, tenofovir. Each drug has advantages and limitations.

IFN and PEG-IFN alpha2a have the advantage of inducing a sustained virologic

response after a defined, limited course of treatment. However, these drugs are

only effective in a minority of patients and have frequent side effects.

Analogues have the advantage of being administered orally, with good safety

profiles and a potent antiviral effect. However, these drugs need to be

administered indefinitely since withdrawal of therapy is generally associated

with reactivation, and a sustained response is uncommon except in HBeAg positive

patients who develop HBe seroconversion. In case of HBe seroconversion, therapy

should usually be continued for at least another 24 weeks. The efficacy of

lamivudine is limited by the emergence of lamivudine-resistant HBV. Adefovir is

associated with a moderate incidence of resistance but its antiviral effect is

not optimal. Entecavir has shown to be more effective with a favourable safety

profile and a low incidence of resistance. Telbivudine is more potent and has a

lower rate of resistance than lamivudine but the resistance rate is

significantly higher than other approved drugs. Tenofovir has a potent antiviral

effect with a good resistance profile. The future of chronic hepatitis B therapy

appears to be different drug combinations. Normally the advantage of drug

combinations versus monotherapy should be additive or synergistic antiviral

effects and a decrease in viral resistance. Unfortunately, there are few data

available and none of the evaluated analogue combinations have been shown to be

better than monotherapy. The only combination which has shown a synergistic

effect is of pegylated interferon alpha2a with lamivudine. Therefore,

combinations of pegylated interferon with the most potent analogues need to be

evaluated. The ultimate goal of therapy is HBsAg seroconversion which is more

often observed with interferon. Indeed, quantification of serum HBsAg will be a

useful tool to predict the treatment outcome. More potent drugs and new

combinations as well as understanding the mechanisms of viral resistance should

be evaluated to improve the efficacy of treatment.

PMID: 18775613 [PubMed - as supplied by publisher]

[Guest guest]

Gastroenterol Clin Biol. 2008 Sep 3. [Epub ahead of print]

[Treatment of chronic hepatitis B.]

[Article in French]

Asselah T, Lada O, Boyer N, ot M, Marcellin P.

Pôle des maladies de l'appareil digestif, service d'hépatologie, Inserm U773

CRB3, université Denis-Diderot-Paris-VII, hôpital Beaujon, 100, boulevard du

Général-Leclerc, 92110 Clichy, France.

In recent years, marked progress has been made in the treatment of chronic

hepatitis B. Several agents have been approved: interferon alpha-(IFN),

pegylated interferon alpha2a (PEG-IFN alpha2a), lamivudine, adefovir, entecavir,

telbivudine and recently, tenofovir. Each drug has advantages and limitations.

IFN and PEG-IFN alpha2a have the advantage of inducing a sustained virologic

response after a defined, limited course of treatment. However, these drugs are

only effective in a minority of patients and have frequent side effects.

Analogues have the advantage of being administered orally, with good safety

profiles and a potent antiviral effect. However, these drugs need to be

administered indefinitely since withdrawal of therapy is generally associated

with reactivation, and a sustained response is uncommon except in HBeAg positive

patients who develop HBe seroconversion. In case of HBe seroconversion, therapy

should usually be continued for at least another 24 weeks. The efficacy of

lamivudine is limited by the emergence of lamivudine-resistant HBV. Adefovir is

associated with a moderate incidence of resistance but its antiviral effect is

not optimal. Entecavir has shown to be more effective with a favourable safety

profile and a low incidence of resistance. Telbivudine is more potent and has a

lower rate of resistance than lamivudine but the resistance rate is

significantly higher than other approved drugs. Tenofovir has a potent antiviral

effect with a good resistance profile. The future of chronic hepatitis B therapy

appears to be different drug combinations. Normally the advantage of drug

combinations versus monotherapy should be additive or synergistic antiviral

effects and a decrease in viral resistance. Unfortunately, there are few data

available and none of the evaluated analogue combinations have been shown to be

better than monotherapy. The only combination which has shown a synergistic

effect is of pegylated interferon alpha2a with lamivudine. Therefore,

combinations of pegylated interferon with the most potent analogues need to be

evaluated. The ultimate goal of therapy is HBsAg seroconversion which is more

often observed with interferon. Indeed, quantification of serum HBsAg will be a

useful tool to predict the treatment outcome. More potent drugs and new

combinations as well as understanding the mechanisms of viral resistance should

be evaluated to improve the efficacy of treatment.

PMID: 18775613 [PubMed - as supplied by publisher]