Current pharmacotherapy for the treatment of chronic hepatitis B

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Expert Opinion on Pharmacotherapy

2003, vol. 4, no. 10, pp. 1821 - 1827

Current pharmacotherapy for the treatment of chronic hepatitis B

M Lagget; M Rizzetto

Abstract

The virological profile of infection with the hepatitis B virus (HBV) is

changing in many parts of the world from the classical hepatitis B e antigen

(HBeAg)-positive serological pattern to a HBeAg-negative pattern, linked to

the replacement of wild-type HBV by HBV variants with mutations in the

core-promoter and in the precore region that prevent the secretion of HBeAg.

The wild-type HBV disease is characterised by steady levels of alanine

aminotransferase (ALT) and high HBV-DNA levels, responding relatively well

to IFN treatment (3 - 5 MU/day or 10 MU every other day for 16 weeks), which

induces anti-HBe seroconversion and normalises ALT levels in 30% of the

adults, with a minimal risk of relapse. Pegylated-IFN appears to have

superior efficacy over conventional IFN-?. Mutant-type disease

(anti-HBe-positive/HBeAg-negative) is less responsive to IFN given for 6 -

12 months. This has led to the use of novel nucleoside analogues, of which

the prototype is lamivudine. The response to lamivudine therapy shares with

IFN a rapid decline in ALT accompanied by an improvement in histology; at

variance with IFN, in HBeAg-positive chronic hepatitis B (CHB) there is

delayed seroconversion to anti-HBe which accumulates over time, the switch

to anti-HBs is more rare and in the long-term, the activity of the drug is

abolished by the emergence of viral mutations (YMDD-motif mutants) that may

rekindle the disease. The combination of IFN plus lamivudine may be more

efficacious than IFN or lamivudine monotherapy. Lamivudine therapy needs to

be prolonged in HBeAg-negative CHB. Short-term lamivudine-therapy is highly

efficacious in preventing HBV reinfection in liver transplants. Recent data

suggest that long-term IFN therapy (24 months) may achieve a response in 30%

of HBeAg-negative patients. The advent of adefovir, an analogue of adenosine

monophosphate, may provide a safer alternative to lamivudine in the control

of HBV disease; the drug is well-tolerated and treatment raises

drug-resistant mutants in < 2% of the patients over 2 years of therapy.

Adefovir provides rescue therapy against YMDD mutants raised by lamivudine

therapy.