EASL Int'l Statement on HBV

liver411

[B]EASL International Consensus Conference Statement on Hepatitis B[/B]

The European Association for the Study of the Liver (EASL) convened a consensus conference on hepatitis B September 13-14, 2002 in Geneva, Switzerland. The purpose of the conference was to define the state of knowledge and to formulate recommendations for the management of patients with hepatitis B.

The outcome of the consensus conference was to be announced at the 38th annual EASL meeting in Istanbul, Turkey in March 2003, but complications arising from the recent US war with Iraq forced cancellation of the EASL conference in that troubled region.  

Now, however, the EASL Jury, a panel of prominent European liver specialists, has formulated and published its consensus statement. The Jury was asked to evaluate the existing scientific data and to write a consensus statement that addressed the following eight questions:

1) What are the public health implications of hepatitis B?

(2) What is the natural history of hepatitis B, what are the factors influencing the disease?

(3) What is the best way to diagnose and classify hepatitis B?

(4) How can transmission of hepatitis B be prevented?

(5) Which patients should be treated?

(6) What is the optimal treatment?

(7) How should untreated and treated patients be monitored?

(8) What are the main unresolved issues?

Following is the “short version” of their comments and recommendations, which appear in the April 2003 issue of The Journal of Hepatology

medline

本文章重要。

全文在 liver411在上面的给出的连接中http://www.hivandhepatitis.com/hep_b/pdf/article.pdf

April 2003 issue of The Journal of Hepatology
这一期的杂志需要关注，
给出对8个问题给出了许多重要权威陈述consensus statement
1) What are the public health implications of hepatitis B?
hbv对公共健康有什么意义？
(2) What is the natural history of hepatitis B, what are the factors influencing the disease?
hbv的自然史，影响因素
(3) What is the best way to diagnose and classify hepatitis B?
hbv最好的诊断，分类方法？
(4) How can transmission of hepatitis B be prevented?
如何预防传播hbv?
(5) Which patients should be treated?
什么样的病人需要治疗？
(6) What is the optimal treatment?
什么是理想的治疗？
(7) How should untreated and treated patients be monitored?
如何监测治疗和不治疗的病人？
(8) What are the main unresolved issues?
目前还有哪些主要未解决问题？

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其中对一个问题的陈述
6. What is the optimal treatment?

什么是理想的治疗？


Patients should be counselled on the risk of transmission
to household, sexual, and professional contacts (grade B).
They should be instructed about safe sex, safe injections,
and (for health care providers) the value of universal precautions
(grade B). Sexual and household contacts should be
vaccinated (grade B). Patients should be advised on minimising
the danger from other factors that might exacerbate
liver damage – such as obesity, hepatotoxic drugs or excessive
alcohol consumption (grade C). They should be vaccinated
against hepatitis A if not already immune and at risk
(grade B). Immunosuppressive therapy of any kind may
adversely affect the course of hepatitis B. If immunosuppressive
treatment is needed, patients should consult a hepatologist
as careful monitoring and antiviral therapy may be
needed (grade D).
Recombinant interferon alpha and lamivudine are
approved for use in many countries. Adefovir dipivoxil is
now approved for use in the USA and Europe. No randomised
controlled trials have compared all three agents. The
bulk of data available refers to monotherapies, and the effi-
cacy of suitable combination therapies is currently being
evaluated. Thus a consensus document that summarises
the optimal treatment of hepatitis B will require regular
revision in the light of new data. Decisions about antiviral
therapy should take into account the limited long-term effi-
cacy of the three main therapeutic agents available, their
side effects, costs and the predictive factors for response.
Full discussion with the patient regarding the pros and cons
of different strategies should lead to a joint decision about
management (grade D).
The following strategies are recommended for patients
with HBeAg-positive moderate or severe chronic hepatitis
without cirrhosis. A 4–6 month course of interferon alpha (5
MU daily or 9–10 MU thrice weekly, or 6 MU/m2 thrice
weekly in children) may be used as initial therapy (grade A).
If interferon is contraindicated, ineffective or poorly tolerated,
lamivudine or adefovir should be considered (grade
B). Lamivudine should be given at a dose 100 mg daily
for at least 1 year (grade A). Adefovir should be given at
a dose 10 mg daily for at least 1 year (grade A). Treatment
with lamivudine or adefovir should be continued for 4–6
months after a virological response is achieved (grade C).
If a virological response is not achieved after 1 year, decision
to continue treatment should weigh the likelihood of a
sustained response against the risk of developing drug resistance
(higher for lamivudine, lower for adefovir), or drug
toxicity (minimal with lamivudine, some concern for renal
function with adefovir) (grade B). If hepatitis relapses on
stopping lamivudine therapy the drug should be reintroduced
as maintenance therapy if drug resistance has not
developed. More information on safety and frequency of
drug resistance with long-term use of adefovir is needed.
For patients with HBeAg-negative moderate or severe
chronic hepatitis without cirrhosis, the following strategies
are recommended. A 12–24 month course of interferon
alpha, 5–6 MU thrice weekly may be considered as initial
therapy (grade B). If interferon is contraindicated, ineffective
or poorly tolerated, lamivudine or adefovir therapy
should be considered (grade B). Lamivudine should be
given at a dose of 100 mg daily (grade A). Adefovir should
be given at a dose of 10 mg daily (grade A). Because
HBeAg is already undetectable the end-points of treatment
are not clearly established. Sustained suppression of HBV
replication is associated with histological improvement and
therefore appears a realistic goal for treatment (grade C).
The optimal duration of therapy is not known. Most patients
will require more than a year of treatment but a decision to
continue treatment beyond 1 year should weigh the likelihood
of benefit against the risk of developing drug resistance
or drug toxicity, similar to the above statement for
HBeAg positive chronic hepatitis B (grade C). If hepatitis
relapses on stopping lamivudine therapy the drug should be
reintroduced as maintenance therapy if the patient has not
developed drug resistance (grade C). Again, more information
is needed on safety and propensity for causing drug
resistance with long-term use of adefovir.
If a breakthrough on lamivudine therapy (for HBeAg–
positive or –negative chronic hepatitis B) is thought to be
due to the emergence of lamivudine-resistant mutants, treatment
options include (grade C): (i) continue lamivudine if
serum HBV-DNA and aminotransferase levels are lower
than they were pretreatment; (ii) discontinue lamivudine
in patients without underlying cirrhosis and who are not
immunosuppressed; and (iii) change to or add adefovir if
available.
Patients with cirrhosis, but without clinical or laboratory
signs of decompensation can be managed like non-cirrhotic
patients (grade A). Particular care should be paid to these
patients, as flares due to antiviral response, antiviral resistance
resistance
or after cessation of treatment can lead to severe
decompensation (grade B). Decompensated cirrhotic
patients should be evaluated for liver transplantation (grade
C). If they show active HBV replication they should receive
antiviral therapy (grade C). The optimal timing of antiviral
therapy depends on the patient’s condition and expected
waiting time for a transplantation. Several options are available
(grade C). (i) Start lamivudine early, in the hope that a
successful virological response may delay or obviate the
need for liver transplantation. Adefovir can be added to or
substituted for lamivudine when lamivudine resistance
develops. (ii) Start lamivudine only when transplant is imminent
(e.g. within the next 6 months). (iii) Use adefovir as firstline
therapy with close monitoring of renal function.
Post-transplant patients with recurrent hepatitis B who
have not previously received lamivudine should be treated
with lamivudine or adefovir (grade C). Breakthrough during
lamivudine therapy should be treated with adefovir (grade
C). Careful monitoring of renal function is required in transplant
patients receiving adefovir.
No clear recommendation can be made at present for
treatment of health care workers with mild hepatitis B.
Patients with moderate to severe chronic hepatitis D
should be treated with interferon alpha, 9 MU (or 5 MU/
m2) thrice weekly, for at least 1 year (grade A). Patients
with biochemical response at the end of treatment, and
those with relapsing hepatitis, may be treated with maintenance
interferon therapy according to the balance
between tolerance to the drug and the severity of the
liver disease (grade C).
If HAART is indicated for a patient coinfected with
HBV and HIV, lamivudine (150 mg bid) should be
included in HAART (grade A). Exacerbation of hepatitis
due to emergence of lamivudine resistant mutants in
patients on HAART can be treated with addition of tenofovir
to the HAART, because tenofovir acts against lamivudine
resistant HBV and HIV (grade C). If HAART is not
indicated do not use lamivudine because HIV drug resistance
develops rapidly when it is used as a monotherapy
(grade A); adefovir should then be used as the first line
anti-HBV agent (grade D).
No clear recommendation can be made for treating hepatitis
B in haemodialysis patients.
In HBV infected patients requiring immunosuppressive
therapy, lamivudine is generally preferable to interferon as
antiviral therapy (grade C). Treatment can be started 2–4
weeks before immunosuppression or at the first sign of an
exacerbation of the hepatitis (grade C). For patients receiving
a finite course of immunosuppression, such as cancer
chemotherapy, it seems sensible to implement antiviral therapy
and to continue for 3–6 months after cessation of
immune suppressive therapy (grade C). In patients who
are to receive life-long immunosuppression (e.g. kidney
transplant recipients), the risk of resistance to lamivudine
is increased (grade B). The role of adefovir in this setting
has not been evaluated. Adefovir may be an alternative to
lamivudine if further data confirm its long-term safety
(grade D).
D. Valla / Journal of Hepatology