RESEARCH LETTER
Non-In asi e Risk S a i ica ion in NAFLD/NASH
Pa ien s o Sc eening EGD
John Romano
1
Thae Abdel a ah
2
Paul P Manka
3
Michael Fuchs
2,4
Wing-Kin Syn
1,5,6
1
Di ision o Gas oen e ology and
Hepa ology, Medical Uni e si y o Sou h
Ca olina, Cha les on, SC, USA;
2
Di ision
o Gas oen e ology and Hepa ology,
Cen al Vi ginia VA Heal h Ca e Sys em,
Richmond, VA, USA;
3
Depa men o
In e nal Medicine, Uni e si y Hospi al,
Knappscha sk ankenhaus, Ruh -
Uni e si y Bochum, Bochum, Ge many;
4
Di ision o Gas oen e ology and
Hepa ology, Vi ginia Commonweal h
Uni e si y, Richmond, VA, USA;
5
Sec ion
o Gas oen e ology, Ralph H Johnson
VAMC, Cha les on, SC, USA;
6
Depa men o Physiology, Facul y o
Medicine and Nu sing, Uni e si y o he
Basque Coun y, Uni e sidad del Pa S
Vasco/Euskal He iko Uni e si a ea
(UPV/EHU), Leioa, Spain
Po al hype ension is a majo complica ion o ci hosis, as i p edisposes pa ien s o
mani es a ions o hepa ic decompensa ion, including he de elopmen o esopha-
geal a iceal bleeding, hepa ic encephalopa hy, and asci es.
1
Esophageal a ices a e
p esen in app oxima ely 50% o pa ien s wi h ci hosis. The mo ali y du ing a
a iceal bleeding e en is high, wi h es ima es anging om 15% o 20%, being
la gely dependen upon whe he pa ien s ha e ecei ed he s anda d o ca e wi h
endoscopic band liga ion, asoac i e d ugs, and an ibio ics.
2
The hepa ic enous
p essu e g adien (HVPG) is conside ed he gold s anda d in asce aining he
p esence o po al hype ension (PH). Clinically signi ican po al hype ension
(CSPH), which is associa ed wi h he de elopmen o he a o emen ioned mani es-
a ions o decompensa ion, has been de ined as an HVPG g ea e han o equal o
10 mmHg. A e a diagnosis o ci hosis, cu en guidelines ecommend sc eening
o esophageal a ices wi h esophagogas oduodenoscopy (EGD). This p ocedu e is
ca ied ou o iden i y pa ien s who a e a isk o a iceal hemo hage and would
bene i om s a ing p ophylac ic he apy wi h be a blockade.
3,4
This p ocedu e
ca ies isks, which include any ype o espi a o y o ca diac supp ession om
anes hesia, in ec ion, bleeding, and pe o a ion. In addi ion, a signi ican majo i y o
pa ien s wi h a ices who a e indeed a high isk o bleeding do no ha e any
symp oms om he a ices hemsel es, making EGD a non-ideal sc eening es .
5
P e ious s udies sugges ha non-in asi e blood-based ma ke s a e use ul o
iden i y pa ien s wi h li e damage ( ib osis o ci hosis) and may iden i y hose
who will de elop complica ions such as li e cance .
6
Examples o hese ma ke s
include he Fib osis-4 Index (FIB-4), which is a non-in asi e es ima e o li e
sca ing in HCV and HBV pa ien s; he NAFLD (Non-Alcoholic Fa y Li e
Disease) Fib osis Sco e (NFS), which is used o es ima e he amoun o sca ing
in he li e based on se e al labo a o y es s; he BARD sco e, based upon BMI,
AST/ALT a io, and he p esence o absence o diabe es; and he AST o Pla ele
Ra io Index (APRI). We e alua ed whe he hese non-in asi e ma ke s and/o any
o he clinical pa ame e s may be used o iden i y pa ien s wi h li e ci hosis who
a e likely o ha e la ge esophageal a ices, and he e o e would bene i mos om
sc eening EGD.
We e ospec i ely e alua ed a coho o non-alcoholic a y li e disease
(NAFLD)/non-alcoholic s ea ohepa i is (NASH) pa ien s a wo e ia y ca e
Ve e ans A ai s (VA) Hospi als be ween Janua y 1s 2017 and Feb ua y 15 h
2021. A o al o 1476 pa ien s was ini ially in es iga ed; howe e , 1221 pa ien s
Co espondence: John Romano
Di ision o Gas oen e ology and
Hepa ology, Medical Uni e si y o Sou h
Ca olina, S om Thu mond Gazes
Ca diac Resea ch Ins i u e 30 Cou enay
D i e Sui e: 249, Cha les on, SC, USA
Email [email p o ec ed]du
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Recei ed: 7 Oc obe 2021
Accep ed: 24 Decembe 2021
Published: 10 Janua y 2022
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we e excluded owing o s age 1 o 2 ib osis on ib oscan
o li e biopsy. Pa ien s who had ad anced li e ib osis o
ci hosis on he basis o elas og aphy measu emen s and/o
li e biopsies we e u he e alua ed. Endoscopic eco ds
o hese pa ien s we e e iewed o he p esence and size
o esophageal a ices. Va iables ha we e collec ed
included ace, sex, BMI, age, li e enzymes (including
AST/ALT), pla ele coun , albumin, u ic acid le els, and
he p esence o absence o como bidi ies, including dia-
be es, o calcula e he BARD sco e, FIB-4, APRI, and
NFS. We also e alua ed he u ili y o he BAVENO VI
expanded c i e ia (pa ien s wi h li e s i ness <20 kPa and
pla ele coun >150,000/µL a e a low isk o ha ing
a ices ha equi e ea men and, he e o e, do no equi e
sc eening EGD) in his coho .
7
Fo y- ou pa ien s me he inclusion c i e ion, which is
de ined as s age 3 o 4 ib osis o ci hosis on he basis o
elas og aphy and/o li e biopsies. These pa ien s we e
di ided in o wo g oups. G oup A: 26 subjec s wi h small
esophageal a ices o no a ices (mean age: 59.3 yea s;
male: 24, emale: 2; A ican Ame ican: 2, Asian: 3,
Whi e: 19); g oup B: 18 subjec s wi h la ge esophageal
a ices (mean age: 65.4 yea s; male: 16, emale: 2;
A ican Ame ican: 1, Asian: 2, Whi e: 15). Pa ien s in
g oup B had signi ican ly highe non-in asi e sco es han
hose in g oup A: FIB-4 (1.87 s 3.28; p<0.001), APRI
(0.39 s 1.08; p<0.001), NFS (0.58 s 1.82; p<0.01), and
BARD (2 s 3; p<0.05). FIB-4 p o ided he o e all highes
AUROC o 0.82 (speci ici y: 77%; NPV: 74%) o he
p esence o la ge a ices. While APRI showed an
AUROC o 0.812 (speci ici y: 100%; NPV: 70%), NFS
had an AUROC o 0.777 (speci ici y: 54%; NPV: 88%),
and BARD p esen ed an AUROC o 0.696 (speci ici y:
65%; NPV: 73%). In addi ion, BAVENO VI expanded
c i e ia we e able o signi ican ly dis inguish be ween
g oups A and B by chi-squa ed analysis (p=0.0139) and
Fishe 's exac es (p=0.0292). We also ound signi ican
di e ences be ween g oups A and B wi h ega d o he
p esence o splenomegaly (p=0.046) and u ic acid le els
(p=0.027). Non-in asi e es s a e inc easingly being used o
s a i y he isks o pa ien s wi h ch onic li e disease. As
hese es s ha e excellen nega i e p edic i e alue, hey a e
gene ally used o iden i y hose who a e unlikely o ha e
signi ican o ad anced li e disease, and he e o e do no
equi e in asi e e alua ion such as a li e biopsy. This
s udy ex ends hei u ili y and sugges s ha he FIB-4 and
APRI may be able o accu a ely iden i y indi iduals likely
o ha e la ge esophageal a ices and who would he e o e
bene i mos om sc eening EGD. The ex ended BAVENO
VI guidelines u he ecommend ha pa ien s wi h li e
s i ness <15 kPa and pla ele coun >150,000/µL can sa ely
a oid endoscopic sc eening o a ices owing o a e y low
p obabili y o hei ha ing la ge a ices ha equi e
ea men .
7
Pe a e al e ospec i ely in es iga ed a la ge
coho and showed ha 58% o EGDs could be spa ed using
he ex ended BAVENO VI c i e ia, while missing only
0.9% o a ices ha would need ea men .
8
Ou da a
build upon his in o ma ion. Addi ional pa ame e s ha
should be in es iga ed o assess o he p esence o absence
o a ices include splenomegaly and u ic acid le els, as
he e was a signi ican di e ence be ween g oups A and B
o bo h o hese ac o s. Findings om a 2021 s udy sug-
ges ha he e is a ela ionship be ween splenomegaly and
NAFLD/NASH.
9
Spleen s i ness on elas og aphy is also a
de eloping non-in asi e indica o o he p esence o
absence o esophageal a ices and should be s udied u he .
O e all, his VA s udy is clinically signi ican because
i may allow p o ide s o be e iden i y indi iduals wi h
ad anced li e disease who a e mos a isk o a iceal
bleed and who need a sc eening EGD. Con e sely, hose
wi h low non-in asi e sco es, FIB-4 <1.45 o APRI <0.5,
o who do no mee BAVENO VI c i e ia, may be able o
a oid unnecessa y EGDs. Fu he p ospec i e s udies wi h
la ge coho s will be needed o alida e hese indings.
E hics and Consen
This s udy was app o ed by he ins i u ional e iew boa d
a he Ralph H Johnson VAMC. Pa ien consen was no
equi ed o e iew medical eco ds and his was no com-
ple ed owing o he ime ame o he s udy (many yea s
and some pa ien dea hs un ela ed o he s udy). Pa ien
consen was ob ained o any necessa y p ocedu e o in e -
en ion ha was included in he s udy. The consen was
ob ained a he ime he o iginal s udy was comple ed.
Pa ien s we e deiden i ied o ensu e ha no pa ien in o -
ma ion was exposed, in compliance wi h he Decla a ion
o Helsinki.
Disclosu e
The au ho s epo no con lic s o in e es o his wo k.
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