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T ansplan a ion DIRECT ■ 2019 www. ansplan a iondi ec .com 1
ISSN: 2373-8731
DOI: 10.1097/TXD.0000000000000954
Recei ed 2 Oc obe 2019.
Accep ed 6 Oc obe 2019.
1 Depa men o Neph ology, Hospi al Vi gen del Rocío, Se illa, Spain.
2 Depa men o Neph ology, Hospi al La Fe, Valencia, Spain.
3 Depa men o Neph ology, Hospi al Clínico San Ca los, Facul ad de Medicina,
Uni e sidad Complu ense, Mad id, Spain.
4 Depa men o Neph ology, Hospi al Vall d’Heb ón, Ba celona, Spain.
5 Depa men o Neph ology, Complejo Hospi ala io A Co uña, A Co uña, Spain.
6 Depa men o Neph ology, Hospi al Uni e si a io Pue a del Ma , Cádiz, Spain.
7 Depa men o Neph ology, Hospi al La Paz, Mad id, Spain.
8 Depa men o Neph ology, Hospi al de C uces, Vizcaya, Spain.
9 Depa men o Neph ology, Hospi al Miguel Se e , Za agoza, Spain.
10 Depa men o Neph ology, Hospi al Ge mans T ías i Pujol, Ba celona, Spain.
11 Depa men o Neph ology, Hospi al Uni e si a io Ca los Haya, IBIMA,
REDinREN RD16/0009/0006, Málaga, Spain.
12 Depa men o Neph ology, Fundación Puig e , REinREN RD16/0009/0019,
Ba celona, Spain.
13 Depa men o Neph ology, Hospi al de Alican e, Alican e, Spain.
14 Depa men o Neph ology, Hospi al Ma qués de Valdecilla, IDIVAL, REDinREN
RD16/0009/0027, San ande , Spain.
15 Depa men o Neph ology, Hospi al Vi gen de la A ixaca, Mu cia, Spain.
16 Depa men o Neph ology, Hospi al del Ma , Ba celona, Spain.
17 Depa men o Neph ology, Hospi al Uni e si a io Reina So ía, Có doba, Spain.
Di ec -ac ing An i i als o he T ea men
o Kidney T ansplan Pa ien s Wi h Ch onic
Hepa i is C Vi us In ec ion in Spain: A Long- e m
P ospec i e Obse a ional S udy
Ca men González-Co illo, MD,1 Isabel Beney o, MD,2 Ana Sánchez-F uc uoso, MD,3
Manel Pe elló, MD,4 Angel Alonso, MD,5 Auxiliado a Mazuecos, MD,6 Ca los Jiménez, MD,7
So ía Zá aga, MD,8 Ja ie Paul, MD,9 Rica do Lauzu ica, MD,10 Domingo He nández, MD,11
Luis Gui ado, MD,12 An onio F anco, MD,13 Juan Ca los Ruiz, MD, PhD,14 San iago Llo en e, MD,15
Ma a C espo, MD,16 Albe o Rod íguez-Beno , MD,17 Ma ía del Ca men de G acia Guindo, MD,18
Ca men Díaz-Co e, MD,19 and Miguel Ángel Gen il, MD1
Kidney T ansplan a ion
Backg ound. Di ec -ac ing an i i als (DAA) allow e ec i e and sa e e adica ion o hepa i is C i us (HCV) in mos pa ien s.
The e a e limi ed da a on he long- e m e ec s o all-o al, in e e on- ee DAA combina ion he apies in kidney ansplan (KT)
pa ien s in ec ed wi h HCV. He e we e alua ed he long- e m ole abili y, e icacy, and sa e y o DAA combina ion he apies
in KT pa ien s wi h ch onic HCV in ec ion. Me hods. Clinical da a om KT pa ien s ea ed wi h DAA we e collec ed
be o e, du ing, and a e he ea men , including i al esponse, immunosupp ession egimens, and kidney and li e unc ion.
Resul s. Pa ien s (N = 226) we e mos ly male (65.9%) aged 56.1 ± 10.9 yea s, wi h a median ime om KT o ini ia ion
o DAA he apy o 12.7 yea s and HCV geno ype 1b (64.6%). Mos pa ien s we e ea ed wi h so osbu i -based he apies.
Rapid i ological esponse a 1 mon h was achie ed by 89.4% o he pa ien s and sus ained i ological esponse by week 12
by 98.1%. Li e unc ion imp o ed signi ican ly a e DAA ea men . Tac olimus dosage inc eased 37% om he beginning
o ea men (2.5 ± 1.7 mg/d) o 1 yea a e he s a o DAA ea men (3.4 ± 1.9 mg/d, P < 0.001). Median ollow-up was
37.0 mon hs (in e qua ile ange, 28.4–41.9) and dea h-censo ed g a su i al was 91.1%. Ad e se e en s esul ing om
DAA ea men , especially anemia, we e epo ed o 31.0% o he pa ien s. Conclusions. Ch onic HCV in ec ion can be
ea ed e icien ly and sa ely wi h DAA he apy in KT pa ien s. Mos pa ien s e ained s able kidney unc ion and imp o ed li e
unc ion. Tac olimus dose had o be inc eased in mos pa ien s, po en ially as a esul o be e li e unc ion.
(T ansplan a ion Di ec 2019;5: e510; doi: 10.1097/TXD.0000000000000954. Published online 18 No embe , 2019.)
18 Depa men o Neph ology, Hospi al Uni e si a io Vi gen de las Nie es,
G anada, Spain.
19 Depa men o Neph ology, Hospi al Cen al de As u ias, REDinREN
RD16/0009/0021, As u ias, Spain.
All au ho s pa icipa ed in esea ch design and con ibu ed wi h da a om
hei espec i e hospi als. J.C.R. collec ed da a and pe o med he ini ial da a
analysis. All au ho s p o ided eedback on he da a esul s. J.C.R. w o e d a
o he manusc ip and all au ho s con ibu ed o and app o ed he inal e sion.
The au ho s decla e no con lic s o in e es .
This wo k was pa ially suppo ed by a g an om he Ins i u o de Salud Ca los
III co- unded by he Fondo Eu opeo de Desa ollo Regional-FEDER, RETICS
(REDinREN RD16/0009). As ellas Pha ma S.A. p o ided inancial suppo o
medical w i ing and edi ing o he manusc ip .
Co espondence: Juan Ca los Ruiz, MD, Depa men o Neph ology, Hospi al
Ma qués de Valdecilla, A . Valdecilla, 25, 39008 San ande , Can ab ia, Spain.
( uizjc@hum .es).
Copy igh © 2019 The Au ho (s). T ansplan a ion Di ec . Published by Wol e s
Kluwe Heal h, Inc. This is an open-access a icle dis ibu ed unde he e ms o
he C ea i e Commons A ibu ion-Non Comme cial-No De i a i es License 4.0
(CCBY-NC-ND), whe e i is pe missible o download and sha e he wo k p o ided
i is p ope ly ci ed. The wo k canno be changed in any way o used comme cially
wi hou pe mission om he jou nal.
10.1097/TXD.0000000000000954
2 T ansplan a ion DIRECT ■ 2019 www. ansplan a iondi ec .com
Kidney ansplan (KT) ecipien s who a e hepa i is C i us
(HCV)-posi i e ha e an inc eased isk o o he in ec-
ions, new-onse diabe es melli us, ca dio ascula diseases,
li e ib osis, g a loss, and mo ali y.1,2 The immunosupp es-
si e egimen equi ed a e ansplan a ion can p omo e i al
eplica ion, leading o p og ession o li e disease o eac i a-
ion o HCV in ec ion and exace ba ion o hepa i is. Ac i e
i al eplica ion a ansplan a ion is an independen isk ac-
o o g a ailu e in his ype o pa ien s.3 Howe e , kidney
ansplan a ion is s ill ecommended, as mo ali y is highe i
con inuing on main enance hemodialysis.4
An i i al he apy based on in e e on (IFN) o iba i in is
no ecommended in pa ien s wi h impai ed enal unc ion
because bo h d ugs a e elimina ed by he kidneys and educed
doses a e equi ed. In KT pa ien s, he he apies based on IFN
ha e been associa ed wi h poo e icacy, low ole abili y, and
inc eased isk o g a ejec ion.2,5
In ecen yea s, he in oduc ion o o al an i i al d ugs ha
di ec ly inhibi i al p o eins ha e e olu ionized he ea -
men o HCV-posi i e pa ien s.6 The i s IFN- ee di ec -
ac ing an i i al (DAA) he apy implemen ed was so osbu i ,
an inhibi o o he i al RNA polyme ase, app o ed by he
US Food and D ug Adminis a ion in Decembe 2013.7
Cu en ly, he e a e 4 majo classes o app o ed DAA d ugs
a ge ing 3 di e en nons uc u al i al p o eins: NS3/4A p o-
ease inhibi o s (eg, simep e i , pa i ap e i , g azop e i , gle-
cap e i , oxilap e i ); NS5A eplica ion complex inhibi o s
(eg, ledipas i , ombi as i , elbas i , dacla as i , elpa as i ,
pib en as i ); non-nucleoside NS5B polyme ase inhibi o s
(eg, dasabu i ); and nucleoside NS5B polyme ase inhibi o s
(so osbu i ). Used in combina ions and wi h/wi hou iba-
i in, hey can o en lead o sus ained i ological esponses
(SVR) >90% in 12 weeks o less among pa ien s ha a e ea -
men naï e,8 compa ed wi h cu a ion a es o 34% in 24–48
weeks wi h p e ious ea men s.9 Compa ed wi h IFN-based
ea men s, he sa e y o o al DAA he apies has been well
es ed on pa ien s wi h enal dys unc ion. Recen ly de el-
oped pangeno ypic DAA combina ions, such as glecap e i /
pib en as i , ha e eme ged as majo ad ances o pa ien s
wi h se e e kidney impai men .10,11 Howe e , he long- e m
ea men e ec s a e s ill poo ly known,12 as d ug–d ug in e -
ac ions a e a possibili y in pa ien s comp omised by o he
diseases.
In KT pa ien s wi h concomi an HCV in ec ion, he ben-
e i s o DAA he apies include a educed isk o g a ejec-
ion compa ed wi h IFN-based he apies, as well as imp o ed
li e unc ion. HCV e adica ion wi h DAA ea men s has
been shown o imp o e signi ican ly he quali y o li e o KT
pa ien s.13 Ano he ad an age o DAA ea men s is ha mo e
HCV-in ec ed kidneys will be a ailable o ansplan s, hus
educing wai ing lis s and ime on hemodialysis o a ec ed
pa ien s.14-16 I could also be expec ed ha he e will be a
educ ion in he numbe o se e e enal impai men pa ien s
ha will equi e a dual kidney and li e ansplan .
The e is a g owing body o e idence ega ding he e icacy
and sa e y o DAAs in KT ecipien s.17-25 The e iew o he
a ailable da a indica es ha DAA he apies can cu e HCV
in mos KT pa ien s (>98%) wi h no majo sa e y-associa ed
conce ns.17,26 They also highligh ed he need o ca e ul moni-
o ing o immunosupp essi e d ug le els sho ly a e DAA
ea men ini ia ion, as well as he need o close collabo a-
ion be ween hepa ologis s and ansplan a ion neph ologis s.
Al hough la ge coho s udies will be needed o assess he
clinical and long- e m bene i s o DAAs in he KT pa ien
popula ion, he Eu opean Associa ion o he S udy o he
Li e and he Spanish Associa ion o he Li e and he Kidney
encou age he use o DAA he apies o he ea men o HCV
in ec ion in ch onic kidney disease.11,27
In his obse a ional, p ospec i e, mul icen e s udy, we
p esen ou esul s o 226 cases o HCV-in ec ed KT ecipi-
en s ea ed wi h DAA. This analysis is an ex ension o a p e-
ious p elimina y epo o 119 cases.18 Ou main objec i e
he e was o in es iga e he long- e m ole abili y, e icacy, and
sa e y o a a ie y o IFN- ee DAA combina ion he apies
cu en ly used in Spanish e e ence hospi als.
MATERIALS AND METHODS
This obse a ional, mul icen ic, p ospec i e s udy included
KT pa ien s om 19 e e ence hospi als h oughou Spain
om Ma ch 2013 o May 2017. All pa ien s we e ≥18 yea s
old, HCV-posi i e a he ime o ansplan , and ecei ed
DAA he apy. The s udy p o ocol was app o ed by he E hics
Commi ee o he Vi gen del Rocío Hospi al, Se ille (Spain).
All eligible pa ien s p o ided w i en in o med consen be o e
unde going s udy- ela ed p ocedu es. The ial was conduc ed
in acco dance wi h he Decla a ion o Helsinki.28
Pa ien s we e ollowed p ospec i ely and clinical, i ologi-
cal, and labo a o y da a we e collec ed a a basal isi be o e
he ea men s a ed, 1 mon h a e ea men s a (be o e
i s inaliza ion), and 1 mon h, 3 mon hs, 1 yea a e he
ea men ended. All da a collec ed by he in es iga o s we e
placed in o a single da abase o u he analysis.
E icacy o he he apy was de ined as he SVR a e 30, 90
(SVR-12), and 365 days o ea men . Sa e y o he he apy
was assessed as a unc ion o enal unc ion (c ea inine, es i-
ma ed glome ula il a ion a e [eGFR]), p o einu ia, immu-
nosupp ession le els, and changes in he diabe es ea men
o diabe ic pa ien s (as judged by he in es iga o ). Risk o
ecu ence was also e alua ed. Fib osis s age was e alua ed by
ansien elas og aphy (Fib oScan). Compliance wi h an i i al
he apy and a e o ad e se e en s we e moni o ed h ough
he ea men du a ion and ollow-up by e iew o clinical
cha s by he clinicians a each o he hospi als.
S a is ical analysis was pe o med using he SPSS 22.0 s a-
is ical so wa e o Windows. All alues we e calcula ed om
he numbe o alid cases (N). Quan i a i e a iables we e
desc ibed as means and s anda d de ia ions o as medians
wi h in e qua ile anges (IQR). Ca ego ical a iables we e
p esen ed as lis s o equencies and p opo ions. Compa isons
o nume ical a iables we e pe o med using he pai ed es
o he Wilcoxon es .
RESULTS
Pa ien Popula ion
This s udy included 226 KT ecipien s wi h ch onic HCV
in ec ion. The basal demog aphic and clinical cha ac e is-
ics o he pa ien s a e shown in Table1. Mos pa ien s we e
male (65.9%) and he mean age was 56.1 ± 10.9 yea s, wi h
a median ime om KT o ini ia ion o DAA he apy o 12.7
yea s (IQR, 6.3–21.9). The median ime o ollow-up a e
ini ia ion o an i i al he apy was 37.0 mon hs (IQR, 28.4–
41.9). Nine een pa ien s we e ecipien s o a combined li e
© 2019 The Au ho (s). Published by Wol e s Kluwe Heal h, Inc. González-Co illo e al
and KT and 4 had simul aneous panc ea ic and KTs. Se en y-
ou pa ien s (32.7%) p esen ed diabe es, which was ea ed
wi h o al an idiabe ics (8.4%), insulin (19.5%), o a combi-
na ion o bo h (2.7%).
Baseline i al geno ypes a e shown in Table1. Geno ype
1b was he mos equen (146 pa ien s, 64.6%). Fi y-se en
pa ien s (25.2%) had ecei ed p e ious HCV ea men .
Fu he , 8 and 6 pa ien s es ed posi i e o hepa i is B i us
and HIV, espec i ely. Thi y- i e pa ien s (15.5%) p esen ed
po al hype ension and 5 pa ien s (2.2%) had hepa ocellula
ca cinoma.
An i i al T ea men s and Vi ological Response
A o al o 11 di e en an i i al egimens we e p esc ibed
in ou coho s udy (Table2). Mo e han hal o he pa ien s
we e ea ed wi h he combina ion o so osbu i and ledipas-
i (118 pa ien s, 52.2%). The combina ion o so osbu i and
iba i in, wi h o wi hou o he DAA, was used in 38 pa ien s
(16.8%). The median ea men du a ion was 12.3 weeks
(IQR, 11.9–15.7 wk). O he 207 pa ien s who comple ed he
ea men , 185 (89.4%) pa ien s achie ed apid i ological
esponse a e 1 mon h o ea men , wi h unde ec able i al
load. A e comple ion o he 12-week DAA ea men , 203
pa ien s (98.1%) achie ed SVR-12. One yea a e he s a o
ea men , he e we e no cases eco ded o in ec ion elapse o
e ea men wi h an i i als.
The e we e 12 pa ien s (5.3%) who discon inued ea men ;
hal o hem had been ea ed wi h he combina ion o ombi-
as i , i ona i , pa i ap e i , and dasabu i . Discon inua ion
was due o pancy openia in 2 pa ien s, neu al oxici y in 3
pa ien s, hepa ic oxici y in 2 pa ien s, and gas oin es inal
oxici y in 1 pa ien ; in 1 pa ien , he eason was no egis-
e ed and he e we e 3 dea hs: 2 due o sepsis and 1 due o
acu e myoca dial in a c ion. In hese cases, he median ea -
men du a ion was 3.3 weeks (IQR, 1.9–12.2).
G a Func ion and Immunosupp ession
Clinical enal and hepa ic pa ame e s be o e and 1 yea
a e he s a o DAA ea men a e shown in Table3. The
indica o s o kidney unc ion wo sened, as eGFR dec eased
signi ican ly (P = 0.003, pai ed es ). Renal unc ion was no
signi ican ly di e en be ween DAA ea men egimens. All
indica o s o li e unc ion p esen ed e y signi ican imp o e-
men s (P < 0.001).
All pa ien s we e on 1 o mo e immunosupp essi e agen s,
o which ac olimus was he mos equen (67.7%, Table1).
Tac olimus ough le els we e educed 1 yea a e he s a o
DAA he apy (7.2 ± 1.9 ng/mL a s a e sus 6.6 ± 2.3 ng/mL,
P = 0.041). The o al daily dose o ac olimus signi ican ly
inc eased 1 yea a e he s a o he ea men (2.5 ± 1.7
e sus 3.4 ± 1.9 mg/d; P < 0.001).
Du ing he median 37 mon hs o ollow-up, he dea h-
censo ed g a su i al was 96.9% a e 1 yea , 96.4% a e
2 yea s, and 91.1% a e 37 mon hs. The causes o g a loss
we e in e s i ial ib osis plus ubula a ophy in 10 pa ien s,
ch onic humo al ejec ion in 3 pa ien s, and c yoglobuline-
mia in 3 pa ien s. Pa ien su i al (DAA- ea ed) was 96.4%
a e 1 yea , 95.8% a e 2 yea s, and 89.1% a e 37 mon hs.
Causes o dea h we e cance (lung and cholangioca cinoma)
in 6 pa ien s, ca dio ascula e en s in 6 pa ien s, sepsis in 5
pa ien s, li e ailu e due o ci hosis in 2 pa ien s, and o he
causes in 4 pa ien s.
Ad e se E en s
A o al o 70 pa ien s (31.0%) epo ed ad e se e en s while
on DAA ea men (Table2). The mos common ad e se e en
was anemia, which was se ious in 25 o he cases and highly
p e alen in pa ien s ea ed wi h iba i in (>60% o pa ien s).
A decline o kidney unc ion was obse ed in 17 pa ien s
(7.5%). Neu openia and h ombopenia we e de ec ed in
3.1% and 5.3% o pa ien s, espec i ely. In addi ion o he
ad e se e en s shown in Table 2, he e we e also epo ed
cases o as henia (4 pa ien s), nausea and omi ing (3 pa ien s),
headache (3 pa ien s), skin ash (2 pa ien s), ac olimus oxic-
i y (2 pa ien s), and hepa o oxici y (2 pa ien s). Toxici y due o
ac olimus was obse ed in 2 o he 16 pa ien s ea ed wi h
ombi as i , i ona i , pa i ap e i , and dasabu i , bu we ound
no o he cases o oxici y in any o he o he DAA ea men s.
DISCUSSION
In his s udy, we desc ibe he esul s o he medium o
long- e m ea men o HCV-in ec ed KT ecipien s wi h he
TABLE 1.
Basal demog aphic and clinical cha ac e is ics, N = 226
Age (y), mean ± SD 56.1 ± 10.9
Gende (male), N (%) 149 (65.9)
P ima y cause o kidney disease, N (%)
Glome uloneph i is 60 (26.5)
In e s i ial 35 (15.5)
Polycys ic kidney disease 20 (8.8)
Diabe ic neph opa hy 16 (7.1)
Sys emic disease 7 (3.1)
Unknown/o he 78 (38.9)
P e ious ansplan s, N (%)
0 150 (66.4)
1 64 (28.3)
2–3 11 (5.3)
Immunosupp essi e ea men , N (%)a
Tac olimus 153 (67.7)
Mycophenola e 151 (66.8)
S e oids 161 (71.2)
Cyclospo ine 37 (16.4)
Aza hiop ine 12 (5.3)
E e olimus 15 (6.6)
Rapamycin 11 (4.9)
HCV geno ype, N (%)
1 1 (0.4)
1a 34 (15.0)
1a/1b 1 (0.4)
1b 146 (64.6)
2 12 (5.3)
3 11 (4.9)
3a 5 (2.2)
4 11 (4.9)
6 1 (0.4)
Unknown/no da a 4 (1.7)
Fib osis, N (%)
0–2 104 (46.1)
3–5 66 (29.2)
Unknown/no da a 56 (24.8)
Pa ien s could ha e mul iple ea men s.
HCV, hepa i is C i us; SD, s anda d de ia ion.
4 T ansplan a ion DIRECT ■ 2019 www. ansplan a iondi ec .com
ecen ly de eloped DAA he apies. The i ological esponse
was e y high (98.1% achie ed SVR-12) and, a e a median
ollow-up o 26.6 mon hs, pa ien and g a su i al we e
>95%. SVR was simila in double li e /kidney o panc eas/KT
pa ien s, sugges ing ha immunosupp ession did no a ec
he e ec i eness o he he apy. Addi ionally, we obse ed
no pos - ea men elapses. One yea a e he an i i al ea -
men , hepa ic unc ion expe ienced signi ican imp o emen s
in mos pa ien s.
The SVR-12 obse ed in ou s udy is compa able o ha
ound in o he se ies, which ange om 91% o 100% in his
pa ien popula ion.20-22,25,29-31 In ou s udy, some pa ien s de el-
oped mild allog a dys unc ion and some pa ien s equi ed
immunosupp ession dose adjus men . One yea a e ini ia-
ion o DAA ea men , ou s udy showed ha ac olimus dose
had o be signi ican ly inc eased o main ain le els wi hin a -
ge anges. Immunosupp essi e dose adjus men in KT o li e
ansplan ecipien s ecei ing DAA has been obse ed p e i-
ously.32-34 I has been sugges ed ha d ug–d ug in e ac ions
could de elop du ing DAA he apy, as he NS3/4A p o ease
inhibi o s a e deg aded in he li e by cy och ome P450, which
also me abolizes calcineu in inhibi o s. Howe e , in ou s udy,
only 50 pa ien s (22%) ecei ed NS3/4A p o ease inhibi o s
simep e i , pa i ap e i , o g azop e i . Ano he possibili y is
ha enhanced li e unc ion is he esul o imp o ed me ab-
olism o he calcineu in inhibi o s as a consequence o he
DAA ea men . P oin lamma o y cy okines may inhibi
cy och ome P450 enzymes du ing HCV in ec ion, which a e
hen es o ed o no mal unc ion a e i us clea ance.32 This
appa en DAA-induced e e sibili y o li e unc ion could be
mo e p onounced in KT pa ien s wi h lowe deg ees o ib o-
sis compa ed wi h hose wi h se e e ib osis o ci hosis.33 In
he non-KT popula ion, he biochemical pa ame e s o li e
unc ion imp o e sho ly a e DAA he apy,35 wi h eg ession
o ib osis, no maliza ion o po al hype ension and li e
s i ness, and inc ease in skele al muscle mass.36-38
Independen o in e en ion, some unc ional de e io a ion
is expec ed in KT pa ien s ollowed in ime, as e lec ed in
hei clinical pa ame e s. In ou s udy, we could no de e mine
i he e had been a p io decline in enal unc ion, o e en an
imp o emen , as no da a we e a ailable be o e DAA ea -
men . The obse ed a ia ion in enal unc ion was no clini-
cally signi ican and he su i al o he ansplan ed kidney
censo ed o dea h, 91.1% a e a median ollow-up o 37.0
mon hs, was high. Likely he elimina ion o he i us sup-
p esses o limi s i s nega i e impac , imp o ing he su i al o
he pa ien and he ansplan ed o gan un il i equals o nea s
ha o he nega i e HCV ecep o s. Ou s udy and o he s
TABLE 2.
DAA ea men s and ad e se e en s, N (%)
T ea men F equencyaDiscon inuedb
Ad e se e en sb,c
Anemia Kidney unc ion decline Neu openia Th ombopenia
So osbu i , ledipas i 118 (52.2) 2 (1.7) 4 (3.4) 9 (7.6) 0 3 (2.5)
So osbu i , simep e i 23 (10.2) 1 (4.3) 0 2 (8.7) 1 (4.3) 1 (4.3)
So osbu i , dacla as i 21 (9.3) 1 (4.8) 1 (4.8) 1 (4.8) 0 0
So osbu i , iba i in, ledipas i 21 (9.3) 2 (9.5) 13 (61.9) 0 4 (19.0) 5 (23.8)
Ombi as i , i ona i , pa i ap e i , dasabu i 16 (7.1) 6 (37.5) 6 (37.5) 3 (18.8) 1 (6.3) 2 (12.5)
So osbu i , i abi in 8 (3.5) 0 6 (75.0) 0 1 (12.5) 0
G azop e i , elbas i 7 (3.1) 0 0 0 0 0
So osbu i , iba i in, dacla as i 5 (2.2) 0 3 (60.0) 1 (20.0) 0 1 (20.0)
So osbu i , iba i in, simep e i 4 (1.8) 0 1 (25.0) 0 0 0
So osbu i 2 (0.9) 0 0 0 0 0
Simep e i , dacla as i , iba i in 1 (0.4) 0 0 1 (100.0) 0 0
To ala226 (100.0) 12 (5.3) 34 (15.0) 17 (7.5) 7 (3.1) 12 (5.3)
aPe cen ages calcula ed o e o al numbe o pa ien s.
bPe cen ages calcula ed o e pa ien s unde his ea men .
cMo e han 1 ad e se e en could occu in he same pa ien .
DAA, di ec -ac ing an i i als.
TABLE 3.
Clinical pa ame e s o kidney and li e unc ion
N P e ea men Pos - ea men aPb
C ea ininec (mg/dL) 147 1.36 (0.51) 1.50 (1.02) 0.016
eGFR (CKD-EPI)c (mL/min/1.73 m2) 198 61.40 (21.45) 58.75 (22.30) 0.003
P o einu iac (mg/24 h) 184 355.18 (538.12) 813.68 (3524.03) 0.586d
GGTe (U/L) 136 60 (34–126) 22 (16–42) <0.001
To al bili ubine (mg/dL) 136 0.61 (0.50–0.87) 0.50 (0.40–0.80) <0.001
ALTe (U/L) 136 52.5 (31.3–84.5) 17 (13.0–25.0) <0.001
aIndica ed pos - ea men alues a e 1 yea a e s a o di ec -ac ing an i i al he apy.
bPai ed es , unless o he wise s a ed.
cMean (SD).
dWilcoxon es .
eMedian (in e qua ile ange).
ALT, alanine ansaminase; CKD-EPI, Ch onic Kidney Disease Epidemiology Collabo a ion; eGFR, es ima ed glome ula il a ion a e; GGT, gamma glu amyl ans e ase; SD, s anda d de ia ion.
© 2019 The Au ho (s). Published by Wol e s Kluwe Heal h, Inc. González-Co illo e al
we e no designed o assess he unc ional e olu ion o he
kidney in he same pa ien be o e and a e ea men (com-
pa ing he slope o loss o eGFR as a p edic o o i s long-
e m su i al). Possibly his issue canno be esol ed di ec ly
and conclusi ely, al hough la ge egis ies could be used o
de elop e ospec i e s udies by ollowing la ge coho s o
pa ien s.
DAA he apy was well ole a ed, as in p e iously epo ed
se ies,17-19,21-25 wi h only 5.3% o he pa ien s discon inu-
ing ea men . Mos common ad e se e en was anemia in
pa ien s ea ed wi h iba i in, a well-known e ec o his
an i i al.39 The highes p opo ion o discon inua ion due o
DAA ad e se e ec s was seen o pa ien s aking he com-
bina ion o ombi as i , i ona i , pa i ap e i , and dasabu-
i (6 pa ien s, 37.5% o all discon inua ions). We did no
egis e he eme gence o se ious in ec ions ha equi ed
hospi aliza ion.
Cu en ly, he Eu opean Associa ion o he S udy o he
Li e ecommends a ixed-dose combina ion o so osbu i
and ledipas i (geno ypes 1, 4, 5, and 6) wi hou he need
o immunosupp essan d ug dose adjus men s in case o
KT pa ien s wi h accep able kidney unc ion.11 Howe e , he
ixed-dose combina ion o glecap e i and pib en as i o 12
weeks, wi h immunosupp essan d ug adjus men s as needed,
is ecommended o pa ien s wi h se e e kidney impai men
(eGFR <30 mL/min/1.73 m2).11 Al hough cu en he apeu ic
p o ocols o KT pa ien s seem highly e ec i e and sa e, i is
likely ha no el combina ion DAA he apies will be de el-
oped in he u u e o hose pa ien s wi h como bidi ies o
e ac o y o ea men .
To da e, his mul icen ic obse a ional s udy o 226
pa ien s e lec ing cu en clinical p ac ices is he la ges o
i s kind in Eu ope and wi h he longes ollow-up (37 mo).
Howe e , he s udy was limi ed by pa ien he e ogenei y (eg,
geno ypes, deg ee o ib osis) and di e si y in DAA egimes,
which p e en ed compa a i e and s a is ically signi ican
analysis o e ec i eness o sa e y.
CONCLUSIONS
Ou s udy con i ms ha HCV in ec ion can be success-
ully and sa ely ea ed a e kidney ansplan a ion wi h a
12-week cou se o ea men wi h DAAs. A e a median ol-
low-up o 37 mon hs, mos pa ien s imp o ed li e unc ion
and e ained clinically s able kidney ac i i y. Pa ien s equi ed
a signi ican inc ease in ac olimus dose o main ain ough
le els wi hou changes in o he immunosupp essi e d ugs.
ACKNOWLEDGMENTS
The au ho s hank F ancisco López de Sa o, PhD, o medi-
cal w i ing suppo wi h he p epa a ion o his a icle.
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