Comment
Eliminating hepatitis B virus as a global health threat
In The Lancet Infectious Diseases, Shevanthi Nayagam
and colleagues1 report a modelling study on the
eectiveness of dierent interventions on the incidence
and mortality rate of chronic hepatitis B virus (HBV)
infection. To appreciate the implications of this
report, we need to understand the context. Chronic
viral hepatitis is the seventh leading cause of death
worldwide.2 Chronic HBV infection alone aects over
240 million people worldwide and is one of the most
common causes of cirrhosis and liver cancer.3 In May,
2014, the World Health Assembly requested WHO
to provide the necessary technical support to enable
member states to develop robust national viral hepatitis
prevention, diagnosis, and treatment strategies. In
response, WHO set ambitious goals of reducing new
cases of chronic viral hepatitis by 90%, and reducing
mortality rates from these infections by 65% between
2015 and 2030.4 Achievement of these goals might at
least eliminate chronic viral hepatitis as a major global
health threat. What can we do to make this happen?
Nayagam and colleagues1 rst assessed the situation
at present and compared it with a hypothetical situation
where no intervention had previously been used to
combat HBV.1 It is gratifying to note that current
interventions have already had a huge impact: averting
210 million new chronic HBV infections by 2015 and
11 million deaths between 2015 and 2030. Nonetheless,
63 million new cases and 17 million HBV-related deaths
will still occur between 2015 and 2030. The authors then
evaluated ve strategies, including scaling-up infant
vaccination coverage to 90%, birth-dose vaccination
coverage to 80%, peripartum antivirals coverage for
mothers with positive hepatitis B e antigen to 80%,
increasing access to antivirals to 80%, and developing
a cure for HBV infection. The rst three interventions
target new infections, whereas HBV treatments prevent
disease progression, cirrhotic complications, and liver
cancer.
Compared with the present state, scaling-up infant
vaccination can prevent 43 million new infections
from 2015 to 2030, but the real impact comes from
birth-dose vaccination, which prevented 187 million
new cases of HBV infection. The smaller eect of infant
vaccination compared with birth-dose vaccination
is because infant vaccination is ineective against
www.thelancet.com/infection Published online September 13, 2016 http://dx.doi.org/10.1016/S1473-3099(16)30214-6
mother-to-child transmission, which is the primary
route of transmission in endemic areas. Even with
vaccination or hepatitis B immunoglobulin at birth,
Ben Curtis/AP/Press Association Images
women with very high viral loads might still transmit
HBV to their children,5 and the use of antivirals during
late pregnancy has been shown to almost eliminate
mother-to-child transmission in this situation.6,7 In
Nayagam and colleagues model,1 peripartum antivirals
can further prevent 06 million new cases. Further
studies are needed to dene the long-term safety of Lancet Infect Dis 2016
peripartum antivirals in mothers and children. Based Published Online
September 13, 2016
on these data, low-income countries should prioritise http://dx.doi.org/10.1016/
birth-dose vaccination over peripartum antivirals if they S1473-3099(16)30214-6
See Online/Articles
do not have the resources to implement both strategies
http://dx.doi.org/10.1016/
at the same time because the birth-dose vaccination will S1473-3099(16)30204-3
have a bigger impact than peripartum antivirals.
Because most cases of cirrhosis and liver cancer
occur during or after middle age, prevention of new
infections will not have a major eect on HBV-related
mortality rates until decades later. Management of
patients who have already been infected is, therefore,
important. Although only one placebo-controlled trial
has used clinical outcomes as the primary endpoint,8
several observational studies suggest that antivirals
can reduce the risk of liver cancer and mortality.9 The
main drawback of antiviral therapy is that long-term
treatment is often needed, but drug resistance and
side eects are rare with entecavir or tenofovir, which
makes long-term treatment acceptable.10 Based on
the estimations in Nayagam and colleagues study,
providing antivirals to 80% of patients with treatment
indications can meet the goal of reducing HBV-
related mortality rate by 65% by 2030. Conversely,
development of a cure for chronic hepatitis B would not
have an additional eect on mortality rate. This is hardly
surprising because the authors assume that adequate
HBV suppression by available antivirals is as eective
as curing HBV. However, antivirals reduce, but do not
eliminate, the risk of liver cancer,11 so the eect of curing
HBV should be revisited when such a drug becomes
available.
We commend the authors for extensively reviewing
data from dierent regions and providing information
that is urgently needed.1 But knowing the eectiveness
of the strategies is only the rst step. The benets
1
 Comment
will not materialise if the interventions are not
implemented. Some policies that sound straightforward
in the developed world can face major hurdles in low-
income and middle-income countries. For example,
the transportation of vaccines to remote areas and
temperature control can already be a challenge, not
to mention the need to train health-care providers
and educate the public. Patient management would
not be possible without access to diagnostic tests
and monitoring instruments. Safe needles and blood
products should be available to all countries. Finally, these
programmes cannot be sustained without adequate
funding. According to Nayagam and colleagues forecast,
the annual expenditure between 2015 and 2030 needed
to achieve the goals will be US$55 billion. Although this
will be a good investment because cirrhosis and liver
cancer could be avoided, governments still need to nd
ways to nance these programmes.
With determination, the WHO 2030 goals for
chronic viral hepatitis can be and should be achieved.
Achievement of this goal calls for concerted eort from
policy makers, clinicians, and societies. The tools to
combat HBV are already at hand, and now is the time for
action.
Grace Lai-Hung Wong, *Vincent Wai-Sun Wong
Department of Medicine and Therapeutics, and State Key Laboratory
of Digestive Disease, The Chinese University of Hong Kong, Shatin,
Hong Kong Special Administrative Region, China
wongv@cuhk.edu.hk
2 www.thelancet.com/infection Published online September 13, 2016 http://dx.doi.org/10.1016/S1473-3099(16)30214-6
GL-HW has served as an advisory board member for Gilead and has received paid
lecture fees from AbbVie, Bristol-Myers Squibb, Echosens, Gilead, Janssen, and
Roche. VW-SW has served as an advisory board member for Gilead and Janssen;
as a consultant for AbbVie, Merck, and NovoMedica; and has received paid
lecture fees from AbbVie, Echosens, Gilead, Merck, and Roche.
Copyright The Author(s). Published by Elsevier Ltd. This is an Open Access
article under the CC BY license
1 Nayagam S, Thursz M, Sicuri E, et al. Requirements for global elimination
of hepatitis B: a modelling study. Lancet Infect Dis 2016; published online
Sept 13. http://dx.doi.org/10.1016/S1473-3099(16)30204-3.
2 WHO. Viral hepatitis. Sept 11, 2015. http://www.wpro.who.int/about/
regional_committee/66/documents/wpr_rc66_04_viral_hepatitis.pdf
(accessed June 23, 2016).
3 Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of
worldwide prevalence of chronic hepatitis B virus infection: a systematic
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4 WHO. Draft global health sector strategies. Viral hepatitis, 20162021.
April 22, 2016. http://apps.who.int/gb/ebwha/pdf_les/WHA69/A69_32-
en.pdf?ua=1 (accessed June 23, 2016).
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