C oss-coun y mig a ion linked o people who injec d ugs challenges
he long- e m impac o na ional HCV elimina ion p og ammes
To he Edi o :
As o 2018, he majo i y o Wes e n Eu opean coun ies –
including Spain – ha e li ed es ic ions o he apy based on
disease se e i y in he con ex o HCV in ec ions.
1
Long o e due,
mos na ional elimina ion p og ammes now also include access
o ca e o people who injec d ugs (PWID),
2
who a e a he co e
o ongoing HCV ansmission.
3
Macías e al.
4
ha e ecen ly
shown in his Jou nal ha high i al cu e a es can be achie ed
in his g oup, he eby p o iding e idence ha a ge ing PWID in
ea men p og ammes is wo hwhile. Howe e , he ex en o
which such na ional e o s can educe he HCV bu den no only
depends on he up ake in o ca e and ea men success a es, i
is also de e mined by he ela i e impo ance o wi hin-coun y
ansmission and i us impo a ion om elsewhe e.
As he ch onic na u e o mos HCV in ec ions hampe s eli-
ably econs uc ing con ac ne wo ks om pa ien in e iews,
i us gene ic da a can be a aluable al e na i e sou ce o in o -
ma ion o elucida ing he geog aphic his o y o i us lineages
(e.g. 5,6). Using such da a, we ha e ecen ly shown ha o
he mos p e alen sub ype among PWID in Spain (40%,
7
),
HCV1a, in ec ions o en link o in ec ions ab oad – in ecen
yea s >50% link o Wes e n Eu opean coun ies, mos ly Eu o-
pean Union (EU) membe s a es – as opposed o o he in ec ions
wi hin Spain.
8
Hence, educing HCV1a p e alence and sp ead
ac oss Eu ope will help o consolida e he impac o Spanish
e o s o educe he HCV bu den.
To in es iga e whe he his is a gene al pa e n ha also
holds o he second mos p e alen sub ype among PWID in
Spain (26.5%,
7
), HCV3a, we analysed newly gene a ed HCV3a
genome da a co e ing pa s o he NS5A and/o NS5B genes
om 196 HCV3a-in ec ed pa ien s sampled be ween Ap il
2014 and Ap il 2017 ac oss Spain (GenBank: accession numbe s
MN227780 - MN228016). O he 60% o whom in o ma ion on
he p obable ou e o ansmission was a ailable, 81.8%
epo ed injec ing d ug use. These sequences we e comple-
men ed wi h a backg ound da ase o publicly a ailable da a
om GenBank ( o alling 2752 axa), and analysed as p e iously
desc ibed.
5,8
The E hics Commi ee o he San Cecilio Hospi al,
G anada, app o ed he s udy, and no in o med consen was
equi ed as pa ien in o ma ion was anonymised and de-iden i-
ied p io o analysis.
As o HCV1a,
8
we ound ha he ansmission ne wo k size
s uc u e is no domina ed by a ew la ge exclusi ely Spanish
ansmission ne wo ks, meaning ha HCV3a ansmission ho
spo s in Spain mo e o en b idge o ne wo ks ab oad a he han
being connec ed domes ically. Whe eas we p e iously ound an
inc easing impo ance o Eu opean lineages in seeding he
HCV1a epidemic in Spain,
8
ou cu en econs uc ions showed
ha HCV3a i us mo emen s om wi hin he EU accoun o
~85% o all mig a ions owa ds Spain, wi h li le luc ua ion o e
ime. The numbe o impo ed HCV3a in ec ions pe yea om
o he EU membe s a es – which is a lowe bound es ima e –
has inc eased on a e age by 1 o 4 pe yea , o alling 125
(95% c edible in e al: 92–158) in oduc ions (Fig. 1). The end
and magni ude a e simila o hose o HCV1a, o which he
numbe o lineage in oduc ions o als 114 (95% c edible in e -
al: 72–156) (Fig. 1).
The Spanish na ional s a egy agains HCV is based on a com-
bina ion o ac o s, including a ocus on inc eased sc eening and
diagnosis, enhancing he ea men in as uc u e, he a ailabil-
i y o imp o ed he apeu ic egimens and a ge ing he g oups
a highes isk o ansmi ing HCV, including PWID.
9–11
Despi e
exis ing challenges and policy di e ences be ween egions, his
mul i ac o ial app oach has led o Spain being one o he ew
coun ies in Eu ope ha a e epo ed o be on ack o mee
he Wo ld Heal h O ganiza ion HCV elimina ion a ge s by
2030.
12
As mo e ecen sub ype 1a and 3a in ec ions a e associ-
a ed wi h illici (injec ing) d ug use (e.g. 3), a ge ing his g oup
ha d i es onwa ds sp ead, and o which Macías e al.
4
ha e
demons a ed ha ea men can be highly e ec i e, is mos
desi able in many coun ies. Howe e , ac oss Eu ope, mos
coun ies ha e ye o emb ace he uni e sal ea men pa a-
digm, and e en mo e a e ye o de elop and implemen a
na ional s a egy owa ds he elimina ion o HCV.
1
Ou cu en
and p e ious esul s
8
illus a e ha in he absence o he la e ,
HCV will apidly be e-seeded in he Spanish PWID popula ion,
challenging he long- e m impac o he cu en Spanish in e -
en ion e o s. This demons a es ha he e a e bene icial
scale-e ec s o implemen ing concu en na ional e o s in
he EU and elsewhe e, wi hou which he ul ima e goal, namely
elimina ing HCV, will likely emain elusi e.
Con lic o in e es
All au ho s ha e no hing o disclose, excep o Fede ico Ga cia,
Joaquin An on-Basan as and Miguel Angel Von Wichmann who
epo g an s and pe sonal ees om Vii Heal hca e, pe sonal
ees om Gilead, pe sonal ees om Abb ie and/o pe sonal ees
om MSD and/o pe sonal ees om Janssen, ou side he sub-
mi ed wo k; and Anne-Mieke Vandamme who epo s g an s
om he Resea ch Founda ion Flande s (FWO), du ing he con-
duc o he s udy (as decla ed in he acknowledgmen s sec ion).
Please e e o he accompanying ICMJE disclosu e o ms o
u he de ails.
Au ho s’ con ibu ions
B am V ancken and Lize Cuype s designed and de eloped he
phylogene ic analysis pipeline, pe o med he phylogeog aphic
analyses and w o e subsequen d a s o he manusc ip . Na alia
Chueca and Ana Belen Pé ez we e esponsible o pe o ming all
Jou nal o Hepa ology 2019 ol. xxx jxxx–xxx
Keywo ds: HCV; PWID; Elimina ion; Na ional s a egy; Spain; Eu opean Union.
JOURNAL
OF HEPATOLOGY
Le e o he Edi o
HCV sequencing expe imen s, and bo h assis ed in w i ing he
manusc ip . Joaquin An on-Basan as, Albe o de la Iglesia, Ja ie
Fuen es, Juan An onio Pineda, F ancisco Téllez, En ique Be nal,
Pila Rincón, Miguel Angel Von Wichman, Ana Fuen es, F an-
cisco Ve a, An onio Ri e o-Juá ez, Miguel Jiménez p o ided
samples om hei clinical cen e o be analysed wi hin his
s udy, and assis ed in w i ing he manusc ip . Anne-Mieke Van-
damme p o ided subs an ial suppo o he phylogene ic com-
pu a ions and assis ed ex ensi ely in w i ing he manusc ip .
Fede ico Ga cia supe ised he design o he analyses, he
sequencing expe imen s and assis ed ex ensi ely in w i ing
he manusc ip .
Acknowledgmen s
The au ho s wish o hank Aida Sel a, Jose de Juan Rami ez, Juan Ca -
los Alados, Ma Masiá, Ma ía José Rios, An onio Collado, Jesús San-
os, Miguel Ga cía del To o, Juan Manuel Pascasio, Jose Miguel
Rosales-Zabal, Magdalena La a, Te esa Aldamiz and Sil ia Ga cia-B
as hey p o ided samples om hei clinical cen e o be analysed
wi hin his s udy. The E hics Commi ee o he San Cecilio Hospi al
in G anada app o ed he s udy. This wo k was suppo ed by he Bij-
zonde Onde zoeks onds KU Leu en (BOF) No. OT/14/115, he Fonds
oo We enschappelijk Onde zoek Vlaande en (FWO) (p ojec s
G066215N and G0E8416N, and a pos doc o al manda e o B am
V ancken), and by g an s om Fondo de In es igacion Sani a ia
(www.isciii.es) (PI15/00713), Plan Nacional de I + D + I, Fondo Eu -
opeo de Desa ollo Regional-FEDER (www. edes/ edes/inicio)
(RD16/0025/0040) and GEHEP-SEIMC (GEHEP-004). Pa o he com-
pu a ional esou ces and se ices we e p o ided by he He cules
Founda ion and he Flemish Go e nmen – depa men EWI-FWO
K edie aan Na o se s (Theys, KAN2012 1.2.249.12). None o he
unding agencies we e in ol ed in he design o he s udy, no in
he collec ion, analysis and in e p e a ion o he da a, he w i ing
o he manusc ip and he decision o submi he manusc ip o
publica ion.
Supplemen a y da a
Supplemen a y da a o his a icle can be ound online a
h ps://doi.o g/10.1016/j.jhep.2019.08.010.
Re e ences
Au ho names in bold designa e sha ed co- i s au ho ship
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1950 1960 1970 1980 1990 2000 2010 2020
Time (yea )
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
Cumula i e # o in oduc ions in o Spain ha o igina e om wi hin Eu ope
sub ype 1a
sub ype 3a
Fig. 1. F equen impo a ion o HCV sub ype 1a and 3a lineages in o Spain
mos ly om o he coun ies wi hin he Eu opean Union. The lines
co espond o he a e age cumula i e numbe o in oduc ion e en s o
hese sub ypes om o he coun ies wi hin he Eu opean Union in o Spain,
wi h he shaded a eas indica ing he unce ain y (95% c edible in e al). G ey
colo s pe ain o sub ype 1a, and blue colo s o sub ype 3a.
Le e o he Edi o
2Jou nal o Hepa ology 2019 ol. xxx jxxx–xxx
B am V ancken
1,#,
⇑
Lize Cuype s
1,#,
⇑
Ana Belen Pé ez
2
Na alia Chueca
2
Joaquin An on-Basan as
3
Albe o de la Iglesia
4
Ja ie Fuen es
5
Juan An onio Pineda
6
F ancisco Téllez
7
En ique Be nal
8
Pila Rincón
6
Miguel Angel Von Wichman
9
Ana Fuen es
2
F ancisco Ve a
10
An onio Ri e o-Juá ez
11
Miguel Jiménez
12
Anne-Mieke Vandamme
1,13
Fede ico Ga cía
2
1
KU Leu en, Depa men o Mic obiology, Immunology
and T ansplan a ion, Rega Ins i u e o Medical Resea ch,
Leu en, Belgium
2
Clinical Mic obiology, Uni e si y Hospi al San Cecilio, Resea ch
Ins i u e Ibs, G anada, Spain
3
Cen o Peni encia io, Albolo e, G anada, Spain
4
Clinical Mic obiology, Hospi al Juan Ramón Jimenez, Huel a, Spain
5
Hepa ology Uni , Hospi al Miguel Se e , Za agoza, Spain
6
In ec ious Diseases Uni , Uni e si y Hospi al o Valme, Se illa, Spain
7
In ec ious Diseases Uni , Uni e si y Hospi al o Pue o Real, Cádiz,
Spain
8
In ec ious Diseases, Uni e si y Hospi al Reina So ía, Mu cia, Spain
9
In ec ious Diseases Uni , Uni e si y Hospi al Donos ia, San Sebas ian,
Spain
10
In ec ious Disease Uni , Uni e si y Hospi al San a Lucía, Ca agena,
Mu cia, Spain
11
In ec ious Diseases Uni , Uni e si y Hospi al Reina So ía, Có doba,
Spain
12
Hepa ology Uni , Hospi al Ca los Haya, Málaga, Spain
13
Cen e o Global Heal h and T opical Medicine, Mic obiology Uni ,
Ins i u e o Hygiene and T opical Medicine, Uni e si y No a Lisbon,
Lisbon, Po ugal
⇑
Co esponding au ho s. Add ess: KU Leu en, Depa men o
Mic obiology, Immunology and T ansplan a ion, Rega Ins i u e o
Medical Resea ch, Leu en, Belgium. LC: Tel.: +32 16 32 11 76 o BV:
+32 16 37 44 00.
E-mail add esses:b am. ancken@kuleu en.be (B. V ancken),
[email p o ec ed] (L. Cuype s).
#
These i s au ho s con ibu ed equally o his a icle.
JOURNAL
OF HEPATOLOGY
Jou nal o Hepa ology 2019 ol. xxx jxxx–xxx 3