| c. |
The recommended
treatment duration for HBeAg-positive chronic hepatitis B is a
minimum of 1 year. Patients in whom HBeAg seroconversion has
occurred should be maintained on treatment for 3-6 months after
HBeAg seroconversion is confirmed (two occasions at least 2
months apart) to reduce post-treatment relapse. Treatment may be
continued in patients who have not developed HBeAg
seroconversion. Treatment may be continued in patients who have
breakthrough infection due to lamivudine-resistant mutants as
long as benefit to the patient is maintained.
|
| d. |
The recommended
treatment duration for HBeAg-negative chronic hepatitis B is
longer than 1 year but the optimal duration has not been
established.
|
| e. |
The recommended
dose of lamivudine for persons co-infected with HIV is 150 mg
twice daily, along with other antiretroviral medications.
|
| |
Adefovir is administered orally. |
| |
|
| a. |
The recommended
adefovir dose for adults with normal renal function is 10 mg
daily. |
| |
|
| b. |
The recommended
treatment duration for HBeAg-positive chronic hepatitis B is a
minimum of 1 year. The benefits versus risks of longer duration
of treatment are unknown. |
| |
|
| c. |
The recommended
treatment duration for HBeAg-negative chronic hepatitis B is
longer than 1 year. Longer duration of treatment is likely
necessary for sustained response but the optimal duration of
treatment and the benefits versus risks of longer duration of
treatment remain to be determined. |
| |
|
| d. |
The recommended
treatment duration for patients with lamivudine-resistant
mutants has not been determined. Long-term treatment is required
particularly for patients with decompensated cirrhosis or
allograft infection. There appears to be no advantage to
continuing lamivudine therapy in patients with compensated liver
disease who have been switched to adefovir. |
| |
|
| |
Thymosin-a1 is
administered as subcutaneous injections. |
| |
|
| a. |
The recommended thymosin-a1 dose is
1.6 mg twice weekly. |
| |
|
| b. |
The recommended treatment duration
for both HBeAg-positive and HBeAg-negative chronic hepatitis B
is 6 months. |
| |
|
| |
Entecavir is
administered orally (available as tablets and solution). |
| |
|
| a. |
Available in 3 dosage form: 0.5 mg film-coated tablet, 1.0 mg
film-coated tablet, 0.05mg/mL oral solution
|
| b. |
Dose
and duration of treatment remain to be settled |
|
|
UNRESOLVED ISSUES NEED
FURTHER STUDY
|
| |
The treatment of
chronic hepatitis B has advanced into the era of nucleos(t)ide
analogues. However, the results are still unsatisfactory. In
particular, the following issues remain unsettled: |
| |
|
| 1. |
Should patients with
an ALT level of <2 X ULN be treated, and if so when and how? |
| |
|
| 2. |
What is the role of
HBV genotypes in therapy? |
| |
|
| 3. |
Which is the first
(line) choice among the currently available direct antiviral
agents? |
| |
|
| 4. |
What is the role of
combination therapy? |
| |
|
| 5. |
Cost-effectiveness
of each therapeutic strategy. |
CONCLUSION
The future of chronic hepatitis B therapy seems to be in the
combination of different drugs shown in table 7. Ideally, the
optimal drugs to combine would meet the following criteria: they
should have different sites of action on HBV DNA replication, a
potent antiviral effect, an excellent safety profile and they should
induce a sustained response with a limited duration of therapy.
Indeed, the concept of combination therapy has been recently
developed in order to increase efficacy and to decrease the
occurrence of viral resistance. However, so far few combinations
have been evaluated. No combination therapy demonstrated a benefit
as compared with monotherapy.
|
Table 7. New approaches to treatment of chronic hepatitis B |
1. New antiviral
agents
l Inhibitors of reverse transcriptase/DNA polymerase, virus
entry, core assembly |
2. Immunomodulatory
therapy
l Cytokines: stimulate TH1 response
l Therapeutic vaccine: CTL epitopes, DNA vaccines, peptide
vaccines with more potent adjuvants
l Monoclonal antibodies |
3. Molecular therapy
l Antisense oligonucleotides, interfering RNA, dominant negative
mutants |
4. Antifibrotic
therapy |
More potent drugs and
new combinations together with the understanding of the mechanisms
of resistance to therapy are important challenges to improve the
efficacy of treatment and decrease in the future the global burden
related to chronic hepatitis B. |
