Ca e o pa ien s wi h li e disease du ing he COVID-19
pandemic: EASL-ESCMID posi ion pape
Tobias Boe le ,
1
Philip N. Newsome,
2,3
Ma io U. Mondelli,
4
Mojca Ma icic,
5,6
Elisa Co de o,
7
Ma kus Co nbe g,
8,9
Thomas Be g
10,
*
Summa y
The co ona i us disease 2019 (COVID-19) pandemic poses an eno mous challenge o heal hca e
sys ems in a ec ed communi ies. Olde pa ien s and hose wi h p e-exis ing medical condi ions
ha e been iden ified as popula ions a isk o a se e e disease cou se. I emains unclea a his
poin o wha ex en ch onic li e diseases should be conside ed as isk ac o s, due o a sho age o
app op ia e s udies. Howe e , pa ien s wi h ad anced li e disease and hose a e li e ans-
plan a ion ep esen ulne able pa ien coho s wi h an inc eased isk o in ec ion and/o a se e e
cou se o COVID-19. In addi ion, he cu en pandemic equi es unusual alloca ion o heal hca e
esou ces which may nega i ely impac he ca e o pa ien s wi h ch onic li e disease ha con inue
o equi e medical a en ion. Thus, he challenge hepa ologis s a e acing is o p omo e elemedi-
cine in he ou pa ien se ing, p io i ise ou pa ien con ac s, a oid nosocomial dissemina ion o he
i us o pa ien s and heal hca e p o ide s, and a he same ime main ain s anda d ca e o pa ien s
who equi e immedia e medical a en ion.
© 2020 The Au ho s. Published by Else ie B.V. on behal o Eu opean Associa ion o he S udy o he
Li e (EASL). This is an open access a icle unde he CC BY-NC-ND license (h p://c ea i ecommons.o g/
licenses/by-nc-nd/4.0/).
In oduc ion
Co ona i us disease 2019 (COVID-19) is caused by
he ecen ly iden ified co ona i us, se e e acu e
espi a o y synd ome co ona i us 2 (SARS-CoV-2).
Symp oms associa ed wi h COVID-19 a e mos ly
e e , i edness and d y cough. Some pa ien s also
de elop symp oms including sho ness o b ea h,
aches, nasal conges ion, so e h oa , anosmia
and ageusia. Nausea, omi ing and dia hoea occu
less equen ly.
1
While symp oms emain mild
h oughou he cou se o in ec ion in he majo i y o
pa ien s, olde pa ien s we e iden ified o be a
highe isk o a a al disease cou se, wi h hype -
ension, diabe es and co ona y hea disease being
he mos equen como bidi ies in hese coho s.
2,3
COVID-19 and he li e
While p e-exis ing li e disease is no specifically
lis ed in he published coho s udies, ele a ed
alanine amino ans e ase (ALT) le els, educed
pla ele coun s and educed albumin le els a he
ime o admission ha e been associa ed wi h
highe mo ali y,
2
al hough no all o hese al e -
a ions a e independen isk ac o s. I emains un-
clea a his ime whe he hese labo a o y es
al e a ions a e a sign o p e-exis ing li e diseases
in pa ien s wi h a mo e se e e cou se o in ec ion,
whe he hey a he eflec li e damage caused by
he i us i sel , o whe he hey mi o a se e e
inflamma o y esponse (hypoalbuminemia) wi h
dissemina ed in a ascula coagula ion ( h ombo-
cy openia). Possibly, pa ien s wi h ad anced
ch onic li e disease a e a inc eased isk o in ec-
ion due o ci hosis-associa ed immune dys unc-
ion.
4
The same could be ue o pa ien s a e li e
ansplan a ion and possibly hose wi h au oim-
mune li e diseases who ecei e immunosupp es-
si e he apies.
Howe e , cu en ly, he e a e only limi ed da a
a ailable linking unde lying li e diseases wi h he
cou se o SARS-CoV-2 in ec ion and he e a e many
open ques ions (Box 1). Ch onic hepa i is B i us
in ec ion o example, which is mo e p e alen in
China han Eu ope, does no appea o a ec he
ou come o COVID-19.
1
In addi ion, al hough he e
is no p oo o his assump ion, immunosupp es-
sion may e en p o ide some p o ec ion om
immunopa hology, which appea s o con ibu e o
lung damage in cases wi h mo e se e e mani es-
a ions o he disease.
5,6
These may be associa ed
wi h a mac ophage ac i a ion synd ome in he
con ex o a hype inflamma o y synd ome cha ac-
e ised by a cy okine s o m wi h mul i-o gan ail-
u e.
7
On he o he hand, sys emic i al in ec ions
a e o en associa ed wi h ansien ele a ions o
ansaminases which may eflec gene al immune
ac i a ion o inflamma ion caused by ci cula ing
cy okines wi hou comp omising li e unc ion, a
phenomenon called “bys ande hepa i is”. This
may also be he case in pa ien s wi h COVID-19
1
Depa men o Medicine II,
Medical Cen e –Uni e si y o
F eibu g, Facul y o Medicine,
Uni e si y o F eibu g, F eibu g,
Ge many;
2
Na ional Ins i u e o
Heal h Resea ch, Bi mingham
Biomedical Resea ch Cen e a
Uni e si y Hospi als Bi mingham
NHS Founda ion T us ,
Bi mingham, UK;
3
Cen e o
Li e & Gas oin es inal
Resea ch, Ins i u e o
Immunology and
Immuno he apy, Uni e si y o
Bi mingham, Bi mingham, UK;
4
Di ision o In ec ious Diseases
and Immunology, Fondazione
IRCCS Policlinico San Ma eo,
Uni e si y o Pa ia, Pa ia, I aly;
5
Clinic o In ec ious Diseases and
Feb ile Illnesses, Uni e si y
Medical Cen e Ljubljana,
Slo enia;
6
Facul y o Medicine,
Uni e si y o Ljubljana, Slo enia;
7
Depa men o Medicine,
Uni e si y o Se ille, Clinical Uni
o In ec ious Diseases Uni e si y
Hospi al Vi gen del Rocio,
Ins i u e o Biomedicine, Se illa,
CSIC, Spain;
8
Depa men o
Gas oen e ology, Hepa ology
and Endoc inology, Hanno e
Medical School, Hanno e ,
Ge many;
9
Cen e o
Indi idualised In ec ion Medicine
(CIIM), Hanno e , Ge many;
10
Di ision o Hepa ology, Clinic
and Polyclinic o
Gas oen e ology, Hepa ology,
In ec ious Diseases, and
Pneumology, Uni e si y Hospi al
Leipzig, Leipzig, Ge many.
*
Co esponding au ho .
Add ess: Uni e si y Hospi al
Leipzig, Depa men o
In e nal Medicine,
Liebigs aße 18, D-04103
Leipzig, Ge many; Tel.: +49
341/97-12200, ax: +49 341/
97-12209.
E-mail add ess: Thomas.Be g@
medizin.uni-leipzig.de
(T. Be g)
Recei ed 25 Ma ch 2020;
ecei ed in e ised o m 31
Ma ch 2020; accep ed 31
Ma ch 2020; a ailable online
2 Ap il 2020
Re iew
whe e li e ailu e has no been specifically epo ed, e en in he
mos se e e and a al cou ses o disease.
1,2
Howe e , signs o
li e dys unc ion may occu in c i ically ill pa ien s wi h COVID-
19,
8
as e iewed in.
9,10
Whe he pa ien s wi h ci hosis and
COVID-19 a e a inc eased isk o decompensa ion o de elop-
men o acu e-on-ch onic li e ailu e (ACLF), as has been shown
o influenza in ec ion,
11
emains o be de e mined. SARS-CoV-2
may also di ec ly in ec li e cells as he ecep o o he i us,
angio ensin-con e ing enzyme 2 (ACE2),
12
has been shown o
be exp essed on cholangiocy es,
13,14
which may explain cases o
i al shedding in o he aeces.
15,16
How a obse a ions om
Asian coho s can be ans e ed o Eu opean popula ions e-
mains o be de e mined, bu i appea s unlikely ha SARS-CoV-2
in ec ion causes li e damage o an amoun ha subs an ially
con ibu es o he o e all disease bu den.
Aside om he di ec implica ions o li e disease on he
cou se o COVID-19 o ice e sa, he e a e se e al addi ional
aspec s ha equi e a en ion. The cu en pandemic and he
amoun o a ailable in o ma ion –including misin o ma ion and
umou s – esul in unce ain ies and conce ns among pa ien s
bu also heal hca e p o ide s. While he h ea ha COVID-19
poses should no be unde es ima ed, i emains impo an o
main ain ca e o pa ien s wi h ch onic li e disease and o
iden i y po en ial ways o p io i ise ca e o hese pa ien s in
imes o limi ed heal hca e esou ces.
Conside a ions o pa ien s wi h ch onic li e disease
and pa ien s a e li e ansplan a ion
The ecommenda ions p o ided he e add ess he specific cha -
ac e is ics o pa ien s wi h li e disease and a e mean o p o ide
addi ional guidance o he ca e o hese pa ien s. Gene al ec-
ommenda ions and guidelines wi h ega ds o p e en ion,
diagnosis and ea men o COVID-19 om local au ho i ies
should be adhe ed o.
Ou pa ien ca e
The managemen and su eillance o pa ien s wi h ad anced
li e disease and hose ecei ing immunosupp essi e ea men
is o en pe o med in la ge uni s o cen es. These ins i u ions,
howe e , a e cu en ly also COVID-19 ho spo s, hus, po en ially
pu ing ou pa ien s wi h ch onic li e diseases a isk o noso-
comial in ec ions. In addi ion, hospi al s a s ace challenges such
as long wo king hou s and e en educed s a fing because o
COVID-19 qua an ining. The e o e, se e al ac o s ha e o be
conside ed by hepa ologis s who p o ide ca e o hese ulne -
able pa ien s. Clea ly, p io i isa ion c i e ia need o be defined o
ou pa ien con ac s. The gene al and specific ecommenda ions
p o ided he e (Fig. 1) canno comp ehensi ely co e all pa ien
coho s and a e no backed up by da ase s. Mo eo e , he p ecise
managemen o hese pa ien s s ongly depends on he local
COVID-19 bu den. In case o COVID-19 in pa ien s wi h mo e
ad anced ch onic li e disease, we ecommend admission o
inpa ien ca e depending on he p esence o ce ain isk ac o s,
which is discussed in mo e de ail in a sepa a e sec ion.
Reduc ion o di ec exposu e
Physical dis ancing has been sugges ed and/o o ficially imple-
men ed in mul iple coun ies ac oss he globe o p e en
dissemina ion o SARS-CoV-2. This measu e aims o p e en a
apid inc ease in SARS-CoV-2 in ec ions in he gene al popula-
ion wi h he o e all goal o minimising he numbe o pa ien s
wi h a se e e cou se o COVID-19 a any one ime, enabling
heal hca e p o ide s o main ain medical/in ensi e ca e o hese
pa ien s. A he same ime, ulne able pa ien coho s should be
p o ec ed om indi iduals wi h po en ial SARS-CoV-2 exposu e
o in ec ion. Thus, in hese pa ien s, he benefi s o main aining
pa ien ca e ha e o be weighed agains he isk o in ec ion.
These conside a ions equi e adap ion o s anda d ope a ing
p ocedu es o ou pa ien ca e, including emodelling o wai ing
a eas o allow su ficien dis ance be ween pa ien s, educ ion o
wai ing imes and encou aging pa ien s o wai ou side whe e e
possible and e en ually be con ac ed by phone. In addi ion,
exposu e o medical s a should be minimised whe e e
possible.
Face- o- ace con ac is he basis o he physician-pa ien e-
la ionships and allows physicians o quickly assess he o e all
condi ion o he pa ien . Howe e , due o he amoun o indi-
idual con ac s, physicians a e a isk o in ec ion and subse-
quen ly also dissemina ion o he i us. Thus, i seems
app op ia e o also limi he amoun o ace- o- ace con ac s o
pa ien s a isk o a mo e se e e cou se o in ec ion. Technical
solu ions a e a ailable o enable emo e physician-pa ien in-
e ac ions and hei benefi s ha e al eady been discussed in he
con ex o he COVID-19 pandemic.
17
Heal h au ho i ies should
be u ged o equip hospi als wi h such sys ems no only o a end
o COVID-19 pa ien s who s ay in qua an ine a home bu also o
ca e o pa ien s ha need o be p o ec ed om a po en ially
ha m ul in ec ion and guide hem h ough he pandemic,
explaining he u u e ea men /managemen s a egies/plan
and p o ide ad ice conce ning gene al p e en ion measu es.
The cu en pandemic clea ly unde lines he impo ance o
making hese echnical solu ions a ailable o heal h ca e p o-
ide s in o de o be be e p epa ed o si ua ions like hese in
he u u e.
Pa ien s wi h compensa ed li e disease
Gene al conside a ions
Visi s o specialised cen es can be pos poned.
Use elemedicine o isi s by phone whe e e possible.
Rou ine labo a o y es ing can be pe o med locally, e.g.
h ough p ima y ca e physician, and i s equency needs
ca e ul indi idual isk-benefi conside a ions.
Box 1. Open ques ions o li e - ela ed basic/ ansla ional esea ch
ega ding COVID-19.
• Hepa obilia y and gas oin es inal ac s as a hub o i al a icking ia
li e and bilia y exc e ion in o he gas oin es inal ac
• In luence o immunosupp ession on cou se o COVID-19
• Ci hosis-associa ed immune dys unc ion and eme gence o p o ec i e
immuni y
• Inna e and adap i e immune ac i a ion o exhaus ion in COVID-19 and
hei impac on ch onic li e disease
• Risk o SARS-CoV-2 induced hepa ic decompensa ion/ACLF o g a
ejec ion
ACLF, acu e-on-ch onic li e ailu e; COVID-19, co ona i us disease 2019;
SARS-CoV-2, se e e acu e espi a o y synd ome co ona i us 2.
Re iew
2JHEP Repo s 2020 ol. 2 j100113
Specific conside a ions
Ch onic i al hepa i is does no appea o inc ease he isk o
a se e e cou se o COVID-19.
1
Use elemedicine/local labo-
a o y es ing o ollow-up isi s in pa ien s unde an i i al
he apy, send ollow-up-p esc ip ions by mail.
Pa ien s wi h non-alcoholic a y li e disease (NAFLD) o
s ea ohepa i is (NASH) may su e om me abolic como -
bidi ies such as diabe es, hype ension and obesi y pu ing
hem a inc eased isk o a se e e cou se o COVID-19.
In pa ien s wi h au oimmune li e disease, we cu en ly
ad ise agains educing immunosupp essi e he apy. Re-
duc ions should only be conside ed unde special ci cum-
s ances (e.g. medica ion-induced lymphopenia, o bac e ial/
ungal supe in ec ion in case o se e e COVID-19) a e
consul a ion o a specialis .
Emphasis on he impo ance o accina ion o S ep ococcus
pneumoniae and influenza.
In pa ien s wi h compensa ed ci hosis, conside delaying
hepa ocellula ca cinoma (HCC) su eillance and sc eening
o a ices. Non-in asi e isk assessmen o he p esence o
a ices should be applied o s a ifica ion ( h ombocy e
coun o Ba eno VI).
18
See also sec ion on “li e - ela ed
diagnos ic p ocedu es”.
Pa ien s wi h decompensa ed li e disease
Gene al conside a ions
Ca e should be main ained acco ding o guidelines bu
conside minimal exposu e o medical s a , by using ele-
medicine/ isi s by phone whe e e possible/ equi ed o
a oid admission.
Lis ing o ansplan a ion should be es ic ed o pa-
ien s wi h poo sho - e m p ognosis including hose
wi h acu e/acu e-on-ch onic li e ailu e (ALF/ACLF), high
model o end-s age li e disease (MELD) sco e
(including excep ional MELDs) and HCC a he uppe
limi s o he Milan c i e ia, as ansplan a ion ac i i ies/
o gan dona ions will likely be educed in many coun ies
and a eas.
Reducing he in-hospi al li e ansplan e alua ion p og am
o he s ic ly necessa y is ecommended o sho en he in-
hospi al s ay and also educe he numbe o consul a ions
in o he depa men s/clinics (i.e. oph halmologic, de ma o-
logic, den al, neu ologic consul a ions can be done in local
ou pa ien se ings).
Emphasis on he impo ance o accina ion o S ep ococcus
pneumoniae and influenza.
Pa ien s wi h ch onic li e disease
(including compensa ed ci hosis)
Pa ien s wi h decompensa ed li e disease
(including hepa ocelulla ca cinoma)
Pa ien s wi h hepa ocellula ca cinoma
All pa ien s wi h ch onic li e disease should adhe e o common ules o physical dis ancing
Pa ien s a e li e ansplan a ion
• Ca e should be main ained acco ding o guidelines
• Minimal exposu e o medical s a , by using
elemedicine/ isi s by phone whe e e possible/ e-
qui ed o a oid admission
• Lis ing o ansplan a ion should be es ic ed o
pa ien s wi h poo sho - e m p ognosis, as
ansplan a ion ac i i ies/o gan dona ions will likely
be educed in many coun ies and a eas
• Reducing he in-hospi al li e ansplan e alua ion
p og am o he s ic ly necessa y is ecommended
o sho en hospi al s ays
• Emphasis on he impo ance o accina ion o
S ep ococcus pneumoniae and in luenza
• Guidelines on p ophylaxis o spon aneous
bac e ial pe i oni is and hepa ic encephalopa hy
should be closely ollowed o a oid admission
• Include es ing o SARS-CoV-2 in pa ien s wi h
acu e decompensa ion o acu e-on-ch onic li e
ailu e
• Main ain ca e acco ding o guidelines
• Minimal exposu e o medical s a , by using
elemedicine/ isi s by phone whe e e
possible/ equi ed o a oid admission
• Emphasis on he impo ance o accina ion
o S ep ococcus pneumoniae and
in luenza
• In s able pa ien s, pe o m local lab es ing
(including d ug le els)
• We cu en ly ad ise agains educing
immunosupp essi e he apy. Reduc ion
should only be conside ed unde special
ci cums ances a e consul a ion wi h a
specialis
• Ca e should be main ained acco ding o
guidelines, including con inuing sys emic
ea men s and e alua ion o li e
ansplan a ion
• Minimal exposu e o medical s a , by using
elemedicine/ isi s by phone whe e e
possible/ equi ed o a oid admission
• In case o COVID-19, ea ly admission is
ecommended. See also sec ion on
“Inpa ien ca e”
• Visi s o specialized cen es can be pos poned
• Rou ine labo a o y es ing can be pe o med
locally/o -si e
• Use elemedicine/ isi s by phone whe e e
possible
Speci ic conside a ions o
Pa ien s wi h i al hepa i is:
• No inc eased isk o a se e e cou se o
COVID-19
• Send ollow-up p esc ip ions o pa ien s on
an i i al he apy by mail
Pa ien s wi h NAFLD o NASH:
• May su e om diabe es, hype ension and
obesi y, pu ing hem a inc eased isk o a
se e e cou se o COVID-19
Pa ien s wi h au oimmune li e disease:
• We cu en ly ad ise agains educing
immunosupp essi e he apy. Reduc ion should
only be conside ed unde special ci cums ances
a e consul a ion wi h a specialis
• Emphasis on he impo ance o accina ion o
S ep ococcus pneumoniae and in luenza
Pa ien s wi h compensa ed ci hosis:
• Conside delaying hepa ocelulla ca cinoma)
su eillance and sc eening o a ices.
Indi idualized and non-in asi e isk assessmen
should be applied o s a i ica ion (see also
sec ion on “Li e - ela ed diagnos ic p ocedu es”)
Speci ic conside a ions o
Pa ien s ac i ely lis ed o ansplan a ion:
• SARS-CoV-2 ou ine es ing should be pe o med
be o e ansplan a ion in bo h dono s and
ecipien s, acknowledging ha nega i e es ing
canno comple ely ule ou in ec ion.
• Consen o diagnos ic and he apeu ic p ocedu es
ela ed o ansplan a ion should include he
po en ial isk o nosocomial COVID-19
• Li ing-dono ansplan a ions should be conside ed
on a case-by-case basis.
Fig. 1. Flow cha o he p io i isa ion o pa ien ca e in pa ien s wi h ch onic li e disease. The indi idual managemen o hese pa ien s s ongly depends
on he local COVID-19 bu den and o ficially implemen ed ules and egula ions. In some coun ies and a eas, main enance o s anda d ca e migh no be able and
ansplan a ion ac i i ies migh be educed. COVID-19, co ona i us disease 2019; HCC, hepa ocellula ca cinoma; NAFLD, non-alcoholic a y li e disease; NASH,
non-alcoholic s ea ohepa i is; SARS-CoV-2, se e e acu e espi a o y synd ome co ona i us 2.
3JHEP Repo s 2020 ol. 2 j100113
Guidelines on p ophylaxis o spon aneous bac e ial pe i o-
ni is and hepa ic encephalopa hy should be closely ollowed
o p e en decompensa ion and a oid admission.
Include es ing o SARS-CoV-2 in pa ien s wi h acu e
decompensa ion o ACLF.
Specific conside a ions o pa ien s ac i ely lis ed o
ansplan a ion
SARS-CoV-2 ou ine es ing should be pe o med be o e
ansplan a ion in bo h dono s and ecipien s, acknowl-
edging ha nega i e es ing canno comple ely ule ou
in ec ion.
Consen o diagnos ic and he apeu ic p ocedu es ela ed
o ansplan a ion should include he po en ial isk o
nosocomial COVID-19.
Li ing-dono ansplan a ions should be conside ed on a
case-by-case basis.
Pa ien s wi h hepa ocellula ca cinoma
Ca e should be main ained acco ding o guidelines including
con inuing sys emic ea men s and e alua ion o li e
ansplan a ion, bu conside minimal exposu e o medical
s a , by using elemedicine/ isi s by phone whe e e
possible/ equi ed o a oid admission.
In case o COVID-19, ea ly admission is ecommended. See
also sec ion on “inpa ien ca e”.
Pa ien s a e li e ansplan a ion
Main ain ca e acco ding o guidelines, bu conside minimal
exposu e o medical s a , by using elemedicine/ isi s by
phone whe e e possible/ equi ed o a oid admission.
Emphasis on he impo ance o accina ion o S ep ococcus
pneumoniae and influenza.
In s able pa ien s: pe o m local labo a o y es ing (including
d ug le els).
We cu en ly ad ise agains educ ion o immunosupp es-
si e he apy. Reduc ion should only be conside ed unde
special ci cums ances (e.g. medica ion-induced lymphope-
nia, o bac e ial/ ungal supe in ec ion in case o se e e
COVID-19) a e consul a ion o a specialis .
19
Li e - ela ed diagnos ic p ocedu es
Endoscopy
Pa ien s wi hou COVID-19: Depending on a ailable esou ces,
sc eening o a ices by esophagogas oduodenoscopy (EGD)
should be ese ed o pa ien s a isk o a iceal bleeding, such
as pa ien s wi h a his o y o a iceal bleeding o signs o sig-
nifican po al hype ension (asci es, h ombocy e coun
<100,000/
l
l). Non-in asi e isk assessmen o he p esence o
a ices should be applied o s a ifica ion ( h ombocy e coun o
Ba eno VI).
Endoscopic e og ade cholangiog aphy (ERC) o dila a ion o
s en eplacemen in pa ien s a e li e ansplan a ion o pa-
ien s wi h p ima y scle osing cholangi is should be pe o med
a e ca e ul indi idual isk-benefi conside a ions, including isk
o nosocomial SARS-CoV-2 in ec ion depending on local COVID-
19 bu den.
Pa ien s wi h COVID-19: Endoscopic p ocedu es a e associa ed
wi h an inc eased isk o dissemina ing SARS-CoV-2. Du ing EGD
o ERC, sp eading o i us-con aining d ople s can occu . In
addi ion, shedding o he i us in he aeces inc eases he isk o
dissemina ion du ing colonoscopy. Thus, indica ions o
endoscopic p ocedu es in pa ien s wi h COVID-19 should be
limi ed o eme gencies such as gas oin es inal bleeding, bac e-
ial cholangi is o o he li e- h ea ening condi ions.
Ul asound (HCC su eillance)
Pa ien s wi hou COVID-19: HCC su eillance can be de e ed
based on a ailable esou ces (including a ailabili y o he a-
peu ic op ions in case o HCC diagnosis) a he cen e and he
indi idual isk assessmen . Pa ien s wi h inc eased isk, such as
pa ien s wi h ele a ed alpha- e op o ein le els, ad anced
ci hosis, ch onic hepa i is B, NASH/diabe es e c., may be p io i-
ised i esou ces a e limi ed.
Pa ien s wi h COVID-19: HCC su eillance should be de e ed
un il a e eco e y.
Li e biopsy
Pa ien s wi hou COVID-19: Recommenda ions s ongly depend
on he local COVID-19 bu den and he indi idual indica ion o
his ological assessmen .
Biopsy should be de e ed in pa ien s wi h
NAFLD o ch onic i al hepa i is ( o g ading/s aging)
mildly ele a ed ansaminases (e.g. ALT <3× he uppe limi
o no mal [ULN]) o unknown ae iology
Biopsy should be pe o med in pa ien s wi h
s ongly ele a ed ansaminases (e.g. ALT >5× ULN) o un-
known ae iology (in case o suspec ed au oimmune
li e disease, ea men wi hou his ological diagnosis can
be conside ed based on indi idual isk-benefi
conside a ions)
li e masses suspicious o malignancy
Pa ien s wi h COVID-19: Li e biopsy should be de e ed in
mos pa ien s as
 ea men /ca e o COVID-19 ou weighs diagnosis o co-
exis ing li e disease
sys emic inflamma ion associa ed wi h COVID-19 will
obscu e ae iology-specific his ologic cha ac e is ics
li e biopsy may ep esen a isk o i al ansmission
(al hough he i us has so a no been de ec ed in li e
issue, he exp ession o i s ecep o on cholangiocy es
sugges s ha he i us migh be p esen in he li e as
well).
Collabo a ion wi h local heal h ca e p o ide s and
p ima y ca e physicians
The necessi y o educe a el and limi isi s o specialised
cen es is a challenge o li e disease pa ien s and local heal h
ca e p o ide s alike. In o de o acili a e decen alised ca e
o hese pa ien s, close collabo a ions be ween specialised
hepa ologis s and local heal h ca e p o ide s is equi ed. This
pe ains o se e al ac o s such as communica ion o immu-
nosupp essi e a ge le els in pa ien s a e li e ans-
plan a ion, managemen o pa ien s wi h se e e ALT ele a ions
o unknown ae iologies and o he s. Thus, we ecommend ha
specialised cen es p o ide easily accessible con ac in o ma-
ion o local heal h ca e p o ide s o acili a e as and un-
complica ed collabo a ion o he benefi o pa ien s wi h li e
diseases.
Re iew
4JHEP Repo s 2020 ol. 2 j100113
Table 1. Selec ed epu posed d ugs ha ha e been sugges ed/discussed o he ea men o COVID-19 and conside a ions o pa ien s wi h li e disease o
a e li e ansplan a ion.
D ug Mechanism o ac ion, a ionale o COVID-19 Conside a ions o pa ien s wi h li e
diseases o a e li e ansplan a ion
Remdesi i NUC/ i al RNA polyme ase inhibi o
(comple ed phase III o Ebola ea men )
Inhibi s SARS-CoV-2 in i o
24
Case epo s wi h COVID-19
26
No ele an d ug-in e ac ions expec ed
34
No expe ience in li e ci hosis bu a NUC migh be sa e han o he
d ug classes based on expe ience wi h NUCs in ch onic hepa i is B
and C
Li e oxici y ([ALT) possible
Chlo oquine/
Hyd oxychlo oquine
35
±
azi h omycin
In e e ence wi h he cellula ecep o ACE2
24
Endosomal acidifica ion usion inhibi o
Gene ally used o ea men o mala ia and
amoebiasis
In i o and in i o da a
32,36
Exclude G6PD deficiency be o e applica ion
D ug-in e ac ions wi h immunosupp essi e d ugs: close
moni o ing o d ug le el is equi ed o cyclospo ine, ac olimus,
si olimus, e e olimus
34
Hyd oxychlo oquine he apy has no been associa ed wi h ALT
abno mali ies and is an ex emely a e cause o clinically appa en
acu e li e inju y (Li e Tox).
Lopina i / i ona i Lopina i / i ona i a e app o ed PIs o HIV
In i o da a, expe ience in pa ien s wi h SARS, case
epo s wi h COVID-19
37
No p o en e ficacy in i o in se e e COVID-19
28
Many cen es ha e discon inued i s use
Known and well-s udied d ug-in e ac ions wi h
immunosupp essi e d ugs. mTOR inhibi o s (si olimus,
e e olimus) should no be co-adminis e ed, close moni o ing
o d ug le el a e equi ed o calcineu in-inhibi o s
(cyclospo in, ac olimus)
34
Da a o pa ien s wi h li e ci hosis exis
38
The isk o lopina i -associa ed hepa o oxici y in pa ien s wi h
e y ad anced li e disease is low
Based on expe ience wi h PIs in HCV, pa ien s wi h
decompensa ed ci hosis should no be ea ed
Tocilizumab Humanised mAb a ge ing in e leukin-6 ecep o
T ea cy okine elease synd ome obse ed in
COVID-19
7
ALT ele a ions a e equen bu clinically appa en li e
inju y wi h jaundice seem o be a e
39
Pa ien s wi h decompensa ed ci hosis should no be ea ed
Conside isk o HBV eac i a ion
40
Me hylp ednisolone
(s e oids) Co icos e oids bind nuclea ecep o s o dampen
p oinflamma o y cy okines
Mos ly used in pa ien s wi h sep ic shock
Cu en ly NOT ecommended by WHO
41
The isk o o he in ec ions (e.g. SBP) and i al shedding may
inc ease in pa en s wi h decompensa ed li e ci hosis
Conside an imic obial p ophylaxis
Conside isk o HBV eac i a ion
Con alescen plasma Case epo s wi h COVID-19
42
No expe ience in pa ien s wi h ch onic li e disease
Umi eno i (A bidol)*May inhibi i al en y in o a ge cells and s imula e
he immune esponse, used o ea influenza in
some coun ies
31
Possible d ug in e ac ions be ween a bidol and CYP3A4
inhibi o s and induce s
43
Po en ially me abolised in li e and in es ines in humans.
Cau ion in pa ien s wi h li e ci hosis
Fa ipi a i / a ila i *Guanine analogue, RNA-dependen RNA
polyme ase (RdRp)- inhibi o , app o ed o
influenza in Japan
P elimina y esul s om a s udy wi h 80
COVID-19 pa ien s
31
Me abolised by aldehyde oxidase and xan hine oxidase. CYP450
isoenzymes a e no in ol ed in he me abolism
Ele a ion o ALT and AST possible.
No da a in ci hosis a ailable
So osbu i *
maybe combina ion wi h
iba i in
Nucleo ide analogue, RdRp-inhibi o
App o ed o ea men o ch onic hepa i is C
In i o da a show binding o SARS-CoV-2 RdRp
44
Good expe ience in pa ien s wi h ch onic hepa i is C including
pa ien s wi h decompensa ed ci hosis
Fo d ug-in e ac ion de ails see
45
Riba i in may cause se e e haemoly ic anaemia
Ba ici inib*Janus kinase inhibi o , migh in e up
endocy osis o he i us and in acellula
assembly o i us pa icles
46
Could a ec bo h inflamma ion and cellula
i al en y
Associa ed wi h ansien and usually mild ele a ions o ALT
47
Pa ien s wi h decompensa ed ci hosis should no be ea ed
Camos a *Blocks se ine p o ease TMPRSS2 in i o which is
equi ed o S p o ein p iming
48
Licensed in Japan o ea men o ch onic
panc ea i is
Pa ien s wi h ch onic i al hepa i is and ci hosis a e excluded om
clinical ial o ch onic panc ea i is.
49
D ug-in e ac ions unknown
(con inued on nex page)
5JHEP Repo s 2020 ol. 2 j100113

Inpa ien ca e
Many pa ien s wi h ch onic li e disease will con inue o equi e
inpa ien ca e du ing he COVID-19 c isis o decompensa ion,
cholangi is, ejec ion o o he complica ions. Gene al measu es
o p e en SARS-CoV-2 exposu e and in ec ion will be o u mos
impo ance o hese pa ien s. Depending on he local in a-
s uc u e, implemen a ion o COVID-19-clean wa ds o hospi als
is wa an ed. Howe e , based on he local COVID-19-bu den, a
sha p sepa a ion o “clean”and “di y”wa ds/hospi als may no
be sus ainable, al hough ecen e idence p o ides somewha
eassu ing da a ega ding he absence o en i onmen al
con amina ion wi h SARS-CoV-2 RNA o inanima e su aces
ou side pa ien ooms.
20
Whe e e possible, pa ien s wi h
ch onic li e disease equi ing inpa ien ca e o non-COVID-19
causes should be admi ed o COVID-19-clean wa ds o hospi-
als. As hese ins i u ions may no be able o p o ide specialised
hepa ology-ca e, simila o ou ecommenda ions on ou pa ien
ca e, we ecommend ha specialised cen es p o ide easily
accessible con ac in o ma ion o acili a e immedia e hepa ol-
ogy consul a ions.
Howe e , due o he con agiousness o he i us, pa ien s
wi h unde lying li e disease will become in ec ed and will
subsequen ly equi e inpa ien ca e o COVID-19. Wi h ega ds
o nosocomial-in ec ions, ecen obse a ions om Spain ha
compa ed pa ien cha ac e is ics be ween pa ien s wi h
communi y-acqui ed influenza and nosocomial-acqui ed influ-
enza could no de ec a significan di e ence be ween hese
coho s wi h ega ds o unde lying ch onic li e disease.
21
Whe he hese obse a ions will also hold up in he con ex o
he COVID-19 pandemic emains o be p o en. Un il u he e -
idence eme ges, we ecommend ha pa ien s wi h ch onic li e
disease and COVID-19 a e admi ed o inpa ien ca e i hey ha e
addi ional isk ac o s o a mo e se e e COVID-19 cou se like
hype ension, diabe es o obesi y, ci hosis, HCC o a pos -
ansplan s a us.
T ea men conside a ions o COVID-19
Al hough he e a e cu en ly no d ugs app o ed o SARS-CoV-2,
se e al epu posed d ugs ha e been es ed in ecen weeks and
many o hem a e s ill unde in es iga ion (see Table 1).
22
Remdesi i ac s as an adenosine-analogue ha induces RNA
chain e mina ion and was ini ially de eloped as an an i i al
agen agains Ebola.
23
I has ecen ly been shown o inhibi a
clinical isola e o SARS-CoV-2 in i o
24
and o educe disease
se e i y o he ela ed MERS-CoV-in ec ion in a non-human
p ima e model in i o.
25
In addi ion, se e al epo s ha e sug-
ges ed clinical e ficacy in pa ien s su e ing om COVID-19.
26,27
Clinical ials a e ongoing o u he e alua e e ficacy in
a ec ed pa ien s. Al hough i ona i -boos ed lopina i showed
some an i i al e ec on SARS-CoV-2 in i o, a ecen ly published
clinical ial in pa ien s wi h se e e COVID-19 showed no e ec
in i o compa ed o no ea men .
28
O he d ugs cu en ly
unde e alua ion include chlo oquine phospha e o hyd oxy-
chlo oquine.
29
Chlo oquine has shown an i i al e ficacy agains
SARS-CoV-2 in i o h ough in e e ence wi h he ACE2- ecep o
media ed endocy osis and is widely used in he ea men o
pa ien s wi h se e e COVID-19 as mono he apy, bu also in
combina ion wi h azi h omycin.
24,30–32
The adminis a ion o
any o hese compounds o in ec ed pa ien s will emain an in-
di idual decision as e ficacy and op imal iming emain o be
cla ified. Howe e , wi h ega ds o pa ien s wi h ch onic li e
disease, possible ad e se e en s ha e o be kep in mind. This is
pa icula ly impo an wi h espec o d ug-in e ac ions in pa-
ien s wi h ce ain immunosupp essi e he apies whe e d ug
le els o cyclospo ine, ac olimus, si olimus o e e olimus will
ha e o be closely moni o ed. In addi ion, pa ien s wi h impai ed
li e unc ion a e a high isk o d ug oxici ies, i.e. in pa ien s
wi h Child-Pugh B/C ci hosis. Table 1 summa ises some con-
side a ions wi h ega ds o po en ial oxici ies in hese pa ien s.
I is also impo an o s ess ha all he d ugs cu en ly unde
in es iga ion a e no app o ed o SARS-CoV-2. Howe e , gi en
ha ea ly ini ia ion o an i i al he apy is known o blun he
cou se o influenza, i is easonable o assume ha ea ly ea -
men ini ia ion migh also be beneficial o p e en se e e
pneumonia in COVID-19. Thus, in pa ien s wi h li e disease and
isk ac o s o a se e e cou se o he disease, we ecommend
inclusion in o ea ly an i i al ea men p og ammes o clinical
ials ha migh be ac i e a di e en cen es.
Gene al conside a ions o pa ien s wi h ch onic li e disease
and COVID-19
Conside ea ly admission acco ding o he p esence o
addi ional isk ac o s and inclusion in clinical ials and
(expe imen al) an i i al he apy o COVID-19 ollowing local
guidelines (see Table 1 o guidance wi h ega ds o CLD)
P e en ace aminophen o e dosing (2–3 g/day is conside ed
sa e in pa ien s wi h ci hosis wi hou ac i e alcohol
consump ion
33
)
Table 1 (con inued)
D ug Mechanism o ac ion, a ionale o COVID-19 Conside a ions o pa ien s wi h li e
diseases o a e li e ansplan a ion
Emapalumab*mAb a ge ing in e e on-gamma
T ea cy okine elease synd ome obse ed in
COVID-19
7
App o ed o haemophagocy ic
lymphohis iocy osis
Clinical ial o COVID-19 planned
50
Associa ed wi h mild and ansien ALT ele a ions ypically a ising a
ew weeks a e s a o ea men
Risk o eac i a ion o ube culosis, pneumocys is ji o ecii,
he pes zos e
Risk o HBV eac i a ion may be lowe
Anakin a*In e leukin 1 ecep o an agonis
Clinical ial o COVID-19 planned
50
Minimal hepa ic me abolism
This lis is no in ended o gi e ea men ecommenda ions. The e idence o use hese d ugs is low. Mul iple RCTs o he abo e-men ioned d ugs and some o he d ugs a e
ongoing in pa ien s wi h SARS-CoV-2 in ec ion.
ACE2, angio ensin-con e ing enzyme 2; ALT, alanine amino ans e ase; AST, aspa a e amino ans e ase; COVID-19, co ona i us disease 2019; NUC, nucleoside analogue; PIs,
p o ease inhibi o s; RdRp, RNA-dependen RNA polyme ase; SARS-CoV-2, se e e acu e espi a o y synd ome co ona i us 2.
*These d ugs a e lis ed o include he mos equen ly discussed agen s o COVID-19. These d ugs may lack clinical e ficacy, and some ha e been conside ed based on in i o
obse a ions o hei mode o ac ion.
Re iew
6JHEP Repo s 2020 ol. 2 j100113
Do no adminis e non-s e oidal an i-inflamma o y d ugs in
pa ien s wi h ci hosis and po al hype ension
33
See also sec ion on “li e - ela ed diagnos ic p ocedu es” o
ecommenda ions on endoscopy, HCC su eillance and li e
biopsy
Specific conside a ions o pa ien s wi h ch onic li e disease
and COVID-19
In pa ien s wi h decompensa ed ci hosis, ea men o
ci hosis-associa ed complica ionssuchaspo alhype ension,
asci es, hepa ic encephalopa hy, spon aneous bac e ial pe i o-
ni is e c. should be con inued.
In pa ien s wi h HCC, loco egional he apies should be
pos poned whene e possible and immune-checkpoin
inhibi o he apy empo a ily wi hd awn. The decision
on whe he o con inue ( educed dose) kinase inhibi o s in
non-se e e COVID-19 should be aken on a case-by-case
basis.
In pa ien s a e li e ansplan a ion, dose adjus men o
calceu in- and/o mTOR- inhibi o s migh be equi ed
depending on he an i i al he apy ini ia ed (Table 1).
Abb e ia ions
ACE2, angio ensin-con e ing enzyme 2; ACE-I, angio ensin-con e ing
enzyme inhibi o ; ACLF, acu e-on-ch onic li e ailu e; ALT, alanine
amino ans e ase; AST, aspa a e amino ans e ase; COVID-19, co ona-
i us disease 2019; EGD, esophagogas oduodenoscopy; ERC, endo-
scopic e og ade cholangiog aphy; HCC, hepa ocellula ca cinoma;
MELD, model o end-s age li e disease; NAFLD, non-alcoholic a y
li e disease; NASH, non-alcoholic s ea ohepa i is; NUC, nucleoside
analogue; PIs, p o ease inhibi o s; RdRp, RNA-dependen RNA poly-
me ase; SARS-CoV-2, se e e acu e espi a o y synd ome co ona i us 2;
ULN, uppe limi o no mal.
Conflic s o in e es
D Be g epo s g an s, pe sonal ees and non-financial suppo om
Gilead. D Boe le epo s consul ancy ees om Gilead. D Co nbe g
epo s pe sonal ees om Gilead. All o he au ho s epo no conflic s o
in e es .
Please e e o he accompanying ICMJE disclosu e o ms o u he
de ails.
Acknowledgemen
We hank Benjamin Maasoumy o c i ically e iewing he manusc ip
and p o iding aluable commen s.
Supplemen a y da a
Supplemen a y da a o his a icle can be ound online a h ps://doi.o g/1
0.1016/j.jhep .2020.100113.
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