Natural course, therapeutic options and economic evaluation of therapies for

liver411

Drugs. 2006;66(14):1831-51.

Natural course, therapeutic options and economic evaluation of therapies for
chronic hepatitis B.

Han SH.

David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

Chronic hepatitis B virus infection afflicts 400 million people worldwide
and untreated will progress to cirrhosis in 15-40% of individuals, with an
associated increased risk for the development of hepatocellular carcinoma.
The 'inactive carrier state' carries a benign prognosis with a very low risk
of cirrhosis or hepatocellular carcinoma. However, the hepatitis B e antigen
(HBeAg)-positive chronic hepatitis state is an active disease state with
increased risk for progressing to cirrhosis and hepatocellular carcinoma.
The HBeAg-negative mutant variety of chronic hepatitis B has been associated
with a higher incidence of cirrhosis at initial presentation and more
frequent progression to hepatocellular carcinoma compared with the wild-type
hepatitis B.Five medications are currently approved by the US FDA for the
treatment of chronic hepatitis B: interferon-alpha, lamivudine, adefovir
dipivoxil, entecavir and peginterferon-alpha-2a. Interferon-alpha therapy
has been shown to increase the rate of HBeAg and hepatitis B DNA loss with a
small chance of hepatitis B surface antigen loss, but has significant
adverse effects and is ineffective against the HBeAg-negative mutant.
Lamivudine is a safely used, orally administered drug with good efficacy,
but is associated with the development of a lamivudine-resistant (Lam-R)
mutant in a large proportion of patients after long-term therapy. High
relapse rates after lamivudine therapy make this medication less effective
in the HBeAg-negative mutant also. Adefovir dipivoxil is a safely used,
orally administered drug, which is effective against the Lam-R mutant.
Adefovir dipivoxil is effective against the wild-type and HBeAg-negative
hepatitis B and has a very low incidence of resistance development.
Entecavir is a highly potent and selective new oral drug against hepatitis
B. It has demonstrated no resistance development in treatment-naive
patients, but a low incidence of resistance in patients infected with prior
Lam-R mutants. Peginterferon-alpha-2a is administered once weekly and has
improved efficacy compared with standard interferon-alpha and lamivudine.
However, it has a similar adverse-effect profile to standard
interferon-alpha.Pharmacoeconomic studies have demonstrated a cost benefit
in treating chronic hepatitis B patients compared with no therapy. However,
results have been conflicting, with earlier studies showing a cost advantage
of lamivudine over interferon-alpha and a more recent, comprehensive study
favouring interferon-alpha monotherapy in HBeAg-negative patients and
adefovir dipivoxil 'salvage' after lamivudine resistance development in
HBeAg-positive patients.

PMID: 17040114 [PubMed - in process

经济，实惠，自然，不耽误....面面俱到，不容易呢。作为参考好了。