|
- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30437
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
|
7. CONCLUSION
Although impressive progress has been made, the intermediate viral hepatitis elimination goals
set by WHO for 2020 have not been achieved. Thus, the 2030 elimination goals will now be more
difficult to achieve, perhaps even unlikely. The low diagnostic rate, limited vaccination coverage,
and limited accessibility of currently approved therapeutics in many developing countries in the
world hamper efforts to reduce the disease burden. Added to this is the coronavirus disease 2019
pandemic, which has stalled clinical trials and frustrated hepatitis outreach programs (148).
For prevention, the currently available vaccines are highly effective and improved strategies
for their delivery that are nation specific will be needed. For the therapeutic component of elim-
ination, which affects between 250 and 300 million people with CHB, new medicines will be
needed. The uptick in the number and diversity of investigational drugs for CHB provides a basis
of optimism. In 2010, for example, there were 3 preclinical- and 11 clinical-stage drugs in de-
velopment, all being largely from the same mechanistic categories. By 2020, as indicated by the
Hepatitis B Foundation (http://www.hepb.org), the number of drugs in development had grown
substantially with 17 preclinical- and 32 clinical-stage drugs, and these drugs are from diverse
mechanisms. This diversity is important because it is quite likely that a combination therapeutic
approach will be needed. Specifically, drugs that suppress the virus as well as those that restore a
beneficial immunological response are likely to be needed.
Importantly, because the percentage of hepatocytes infected with HBV can be quite high in
those with CHB, there are safety concerns that functional restoration of HBV-specific T cells
or blockage of immune regulatory pathways could lead to massive hepatocellular damage with
clinical liver decompensation. In this regard, considerations must be given during therapeutic de-
velopment and treatment to the underlying hepatic functional reserve of the patient, the burden
of the virus as well as the proportion of HBV-infected hepatocytes, and the balance between cy-
topathic and noncytopathic mechanisms that is needed to cure CHB safely. In seems likely that
suppression of HBV protein expression and decrease of infected cell number with direct-acting
antivirals will be an important combination component of immune activation therapies. There-
fore, despite the challenges inherent to the ambitious WHO plans, a road map toward elimination
of HBV now exists and if followed should eventually reduce, if not eliminate, the public health
problem of HBV and the diseases with which it is associated.
DISCLOSURE STATEMENT
T.M.B. and J.-T.G. receive research support from and hold stock in Arbutus Biopharma, Inc.
K.-M.C. serves as a member of the scientific advisory board of Arbutus Biopharma, Inc |
|
发表于 2021-9-30 16:13
