psyg-09-02666 Janua y 4, 2019 Time: 10:45 # 1
MINI REVIEW
published: 09 Janua y 2019
doi: 10.3389/ psyg.2018.02666
Edi ed by:
And ew Kemp,
Swansea Uni e si y, Uni ed Kingdom
Re iewed by:
Isabel Ma ques B andão,
Uni e si y o Po o, Po ugal
Vic o Cláudio,
Ins i u o Uni e si á io de Ciências
Psicológicas, Sociais e da Vida,
Po ugal
*Co espondence:
Da id Pi es Ba ei a
[email p o ec ed]
Special y sec ion:
This a icle was submi ed o
Clinical and Heal h Psychology,
a sec ion o he jou nal
F on ie s in Psychology
Recei ed: 10 Ap il 2018
Accep ed: 11 Decembe 2018
Published: 09 Janua y 2019
Ci a ion:
Ba ei a DP, Ma inho RT, Bicho M,
Fialho R and Ouakinin SRS (2019)
Psychosocial and Neu ocogni i e
Fac o s Associa ed Wi h
Hepa i is C – Implica ions o Fu u e
Heal h and Wellbeing.
F on . Psychol. 9:2666.
doi: 10.3389/ psyg.2018.02666
Psychosocial and Neu ocogni i e
Fac o s Associa ed Wi h
Hepa i is C – Implica ions o
Fu u e Heal h and Wellbeing
Da id Pi es Ba ei a1*, Rui Ta o Ma inho2, Manuel Bicho3, Rena a Fialho4and
Sil ia Raquel Soa es Ouakinin5
1Clínica Uni e si á ia de Psiquia ia e Psicologia Médica, Faculdade de Medicina, Uni e sidade de Lisboa, Se iço
de Gas en e ologia e Hepa ologia, Cen o Hospi ala Lisboa No e-Hospi al de San a Ma ia, Lisbon, Po ugal, 2Faculdade
de Medicina, Uni e sidade de Lisboa, Se iço de Gas en e ologia e Hepa ologia, Cen o Hospi ala Lisboa No e-Hospi al
de San a Ma ia, Lisbon, Po ugal, 3Labo a ó io de Gené ica, Faculdade de Medicina, Ins i u o de Saúde Ambien al,
Uni e sidade de Lisboa, Lisbon, Po ugal, 4Asse i e Ou each Team, Sussex Pa ne ship NHS Founda ion T us ,
B igh on and Ho e, Uni ed Kingdom, 5Clínica Uni e si á ia de Psiquia ia e Psicologia Médica, Faculdade de Medicina,
Uni e sidade de Lisboa, Lisbon, Po ugal
Backg ound: Hepa i is C i us (HCV) in ec ion in ol es changes no only om he poin
o iew o physical heal h, bu also emo ional, and social ha ha e a signi ican impac on
he quali y o li e o hese pa ien s. Acco ding o he li e a u e e iew, i seems ha he e is
an impo an associa ion be ween psychosocial ac o s, in pa icula on a cogni i e le el
and disease p og ession. The aim o his mini- e iew is o summa ize ecen li e a u e
looking a he associa ions be ween psychosocial and neu ocogni i e ac o s and HCV.
Me hods: PubMed/Medline was sys ema ically sea ched o psychosocial and
neu ocogni i e ac o s associa ed wi h hepa i is C, ea men adhe ence, and pa ien
wellbeing.
Resul s: Pa ien s p esen wi h a ange o ex ahepa ic symp oms including a igue,
anxie y, dep ession, and neu ocogni i e dys unc ion. HCV’s impac on quali y o li e and
wellbeing has se ious clinical and social implica ions.
Conclusion: Hepa i is C and i s managemen con inue o ha e a p o ound impac on
heal h and psychologic wellbeing. Conside ing he se ious ex ahepa ic implica ions
o indi iduals, i is impe a i e ha heal hca e p o essionals pay close a en ion o
psychosocial and neu ocogni i e ac o s. The ocus on combined clinical app oaches
could enhance unde s anding abou he heal h and social impac s o hepa i is C along
he li e cou se.
Keywo ds: hepa i is C, neu ocogni ion, adhe ence, wellbeing, psychosocial ac o s
INTRODUCTION
The Wo ld Heal h O ganiza ion (WHO) es ima es ha abou 3% o he wo ld popula ion (170
million people) is in ec ed wi h he hepa i is C i us (HCV) (WHO, 1999). The disease’s po en ial
o e olu ion owa d ch onici y, hepa ic ci hosis, and hepa ocellula ca cinoma makes his he
main indica o o a li e ansplan (Ma inho and Ba ei a, 2013) be o e e ec i e he apies a ise.
T ea men o HCV changed in he las yea s om an in e e on and iba i in-based he apy o
being in e e on- ee. These a e simple o al egimens, sho e o adminis e wi h e y high e icacy
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Ba ei a e al. Psychosocial, Neu ocogni i e Fac o s and Hepa i is C
a es and be e side e ec p o iles (Smi h e al., 2015). Howe e ,
as ad ances in he ea men o HCV occu , i is impe a i e o
e alua e clinical ou comes, assessing and quan i ying he e icacy
and impac o hese egimens.
The iden i ica ion o neu opsychia ic and neu ocogni i e
symp oms is impo an du ing and be o e ea men ; howe e ,
hey s ill ha e li le ecogni ion o impac in clinical e alua ion.
Fu he , hese symp oms (dep ession, cogni i e diso de s) a e
e en ually associa ed o di ec HCV neu o oxici y (Adinol i e al.,
2015), nega i ely a ec ing he indi idual’s pe cei ed Quali y o
Li e (QoL), daily unc ioning, wo k, and p oduc i i y. These
ac o s can lead o educed in ol emen in medical ca e and li e
p ojec s as well as inc eased mo bidi y and mo ali y, dec easing
o e all wellbeing, QoL, as well as ea men adhe ence (Younossi
e al., 2007;Schae e e al., 2012;Adinol i e al., 2015;Monaco
e al., 2015;Younossi and Hen y, 2015;Chasse e al., 2017).
In a biopsychosocial model o he disease and he ea men ,
i is essen ial o unde s and HCV’s clinical and social impac
on a b oade li e pe spec i e and how indi iduals expe ience
i . The basic p inciples o his model, which uses a holis ic
app oach ega ding illness, includes he biological, psychological,
and social dimensions o he pe son’s li e and he pe cep ion ha
he pe son su e s as a whole. The pe sonali y and he emo ional
ese es o he pa ien as well as he pa icula en i onmen al
condi ions in which he pe son li es should be aken in o
accoun (Papadimi iou, 2017). On he o he hand, posi i e
psychology and ocusing on wellbeing ha e inspi ed esea ch
in o he aspec o he ela ion be ween emo ion and heal h;
namely, he ela ionship be ween subjec i e wellbeing and heal h
ou comes (Okely and Gale, 2015). Wellbeing, in he con ex o
a ch onic condi ion such as HCV in ec ion, mus ollow he
WHO’s inclusi e de ini ion o heal h and s a es o wellbeing
(Misselb ook, 2014). The li e a u e explains his cons uc as
a combina ion o h ee di e en dimensions, each cap u ing a
di e en aspec : li e e alua ion (quali y o goodness o ones’ li e
and o e all li e sa is ac ion), hedonic wellbeing, and eudemonic
wellbeing. The hedonic dimension e e s o he expe ience o
posi i e and nega i e a ec (e.g., sadness o happiness) and
no o a unique posi i e a ec i e alence, while he eudemonic
dimension cap u es meaning and pu pose in li e (S ep oe e al.,
2015). Thus, he aim o his a icle is o de e mine wha is
cu en ly known abou neu ocogni i e and psychosocial ac o s
associa ed wi h HCV as well as o y o alue disease adjus men
and he implica ions o heal h and wellbeing.
METHODS
The aim o his mini- e iew is o summa ize he mo e ecen
li e a u e in es iga ing he ela ionship be ween psychosocial and
neu ocogni i e ac o s associa ed wi h HCV and hei impac on
pa ien wellbeing. We sea ched he Medline/PubMed da abases.
No ime pe iod limi s we e placed, and he key e ms included
“psychosocial,” “neu ocogni i e,” “hepa i is C,” and “wellbeing.”
In addi ion o his selec ion, some esea ch ga he ed ou side his
sea ch was epo ed as e idence, i conside ed app op ia e by all
au ho s.
PSYCHOSOCIAL FACTORS AND
HEPATITIS C
The ch onic na u e and indi idual expe ience o he disease
a e condi ioning ac o s on QoL, wi h clinical and social
implica ions, due no only o he diagnos ic bu also o i s
e olu ion (Neg o e al., 2015;Chasse e al., 2017;I iana e al.,
2017). Se e al s udies ha e s a ed ha ch onic hepa i is C may
lead o se e al complica ions anddespi e he ac ha mos o he
pa ien s wi h HCV a e asymp oma ic, hey consis en ly epo
a signi ican educ ion in heal h- ela ed QoL, when compa ed
wi h he gene al popula ion (Baune and Ai , 2016;Adinol i e al.,
2017).
Psychosocial ch onic s esso s a e well documen ed as
de e minan s o poo men al and physical heal h, leading o an
impo an bu den in heal h sys ems, mo ali y, mo bidi y, and
psychological wellbeing, p edominan ly in de eloped socie ies
(Ya lo e al., 2017). The ela ionship be ween physical men al
and social heal h as well as he unce ain ies abou ea men and
HCV ha e been well documen ed, bo h in he pas and in ecen
li e a u e (Hong e al., 2011;Kleinman e al., 2012;A ms ong
e al., 2016). Emo ional dis ess and dep essi e diso de s ha e
been epo ed in un ea ed HCV pa ien s, poin ing o a possible
ole o he i us i sel in hei occu ence (Ala i e al., 2012;
El Khou y e al., 2012). Fu he mo e, s udies sugges ha a
de iciency o social ela ionships is a signi ican isk ac o
o b oad-based mo bidi y and mo ali y as well as nega i e
implica ions o heal h (Cacioppo and Cacioppo, 2014;Val o a
e al., 2016). Whe he hese diso de s a e due o he unce ain y
o li ing wi h a ch onic disease wi h po en ially li e- h ea ening
complica ions o o o he psychosocial ac o s, emains unde
discussion.
Ano he ele an ac o is he s igma associa ed wi h HCV,
which may inc ease anxie y le els and he ea o ansmi ing
he i us. This ea may be he main cause o social isola ion
and dec eased in imacy in ela ionships (Younossi e al., 2007;
A ms ong e al., 2016). S igma may be de ined as a clus e
o a i udes exp essed by a dominan g oup, which sees o he
indi iduals’ beha io s as being socially unaccep able. The no ion
o s igma, ela ed o shame ul ela ionships, and de ia ions
om wha is conside ed o be he “no m,” has a long his o y
in he con ex o in ec ious diseases, as in he case o HCV
(Boga e al., 2008). These no ms, beha io s, and belie s may
lead o aliena ion o amily and social ela ionships as well as
( eal o pe cei ed) o disc imina ion a heal h se ings o he
wo kplace.
S igma iza ion a ec s no only pa ien s bu also heal h ca e
p o essionals who a e no immune o s e eo ypes and judgmen s
ha may in luence ea men . These issues can p omo e an
inc ease in pa ien s’ isola ion, in he apeu ic con inui y, and a
dec ease in he sea ch o medical help (Bu , 2008). Fu he mo e,
se e al s udies ha e sugges ed ha s igma is associa ed wi h low
ea men adhe ence (Kama ado a e al., 2016), including in
HCV pa ien s (T eloa e al., 2013). Implemen ing psychological
s a egies and in e en ion models (e.g., psychoeduca ion;
in o ma ion-mo i a ion-beha io al skills) should be a majo
conce n.
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Ba ei a e al. Psychosocial, Neu ocogni i e Fac o s and Hepa i is C
A ecen sys ema ic e iew has shown ha non-adhe ence o
he HCV ea men egimen is associa ed wi h i ologic esponse
ailu e (Lie eld e al., 2013), suppo ing ha op imal adhe ence
is needed o achie e ea men success in his a ea (Ma hes
e al., 2014). This also becomes a public heal h issue, since non-
adhe ence a o s he de elopmen and sp ead o esis an HCV
mu a ions, highligh ing adhe ence’s c ucial ole in ea men
success (Weiss e al., 2009).
In es iga ions abou medica ion adhe ence indica e he need
o analyze in e connec ed ac o s ela ed o he complexi y o
he apeu ic egimes ( ea men o HCV and como bidi ies),
ele ance o side e ec s (nausea, p u i us, insomnia, dia hea,
and as henia) (Feld e al., 2014), bu also pa ien - ela ed
a iables. Resea ch poin s o a s eady co ela ion be ween
indi idual cha ac e is ics, illness beha io s, heal h li e acy, and
low adhe ence o ea men . Among sociodemog aphic and
clinical ac o s, gende , dep ession, psychia ic diagnosis in
gene al, illici d ug use, HIV co-in ec ion, ea men egimen,
and hemoglobin le el we e iden i ied as being signi ican ly
and consis en ly associa ed wi h adhe ence/non-adhe ence. Age,
ace, unemploymen , being unma ied, geno ype, ea men
expe ience, disease se e i y, and HCV- ela ed cos s we e
classi ied as inconsis en p edic o s o non-adhe ence (Lie eld
e al., 2013;Ma hes e al., 2014).
F om a psychological poin o iew, ac o s such as
in o ma ion, pe sonal belie s, pe sonali y ai s, social con ex
and he way hey in e ac owa d heal h-p omo ing beha io s,
allow a be e unde s anding o adhe ence bases, helping
o implemen indi idualized adap i e s a egies. Fu he , he
gene al physical symp oma ology ela ed o HCV can a y
om musculoskele al discom o o ch onic a igue (A ms ong
e al., 2016). In a ecen s udy, Bosca ino e al. (2015) epo ed
ha poo physical heal h in pa ien s wi h HCV was associa ed
wi h demog aphic ac o s, including income, heal h insu ance
s a us, ma i al s a us, and also connec ed wi h s ess ul li e
e en s, social suppo o ha ing a li e ansplan . Despi e he
needed le el o adhe ence (95% o highe ), non-adhe ence should
no be a ac o o exclusion o ini ia e an i i al ea men ,
bu a he a ac o ha induces a ca e ul e alua ion in he
s age o p e-p esc ip ion, as well as he implemen a ion o
s a egies designed o p omo e adhe ence in he con ex o
a mul i-disciplina y eam. Thus, we a gue ha an in eg a ed
medical and psychological app oach is undamen al, being
associa ed wi h a highe adhe ence and o a be e he apeu ic
esponse.
The ollowing s eps ha e p o en o be c ucial o he success
o he ea men : o e alua e he pa ien ’s p epa a ion o s a
and adhe e o he he apeu ic egime, o choose a he apeu ic
egime ha may imp o e adhe ence, and o selec and o apply
in e en ions du ing he he apeu ic egime.
Hepa i is C i us diagnosis is epo ed by indi iduals
as ha ing a p o ound impac on hei social unc ioning
and wellbeing. Psychosocial ac o s (social suppo , coping
mechanisms) no only in e e e in he way he subjec
in e p e s and expe iences symp oms, bu hey also in luence
he medical ea men and modi y beha io s (Bielski and Chan,
1976).
NEUROCOGNITION AND HEPATITIS C
The in ol emen o he cen al ne ous sys em (CNS), ound
in ecen s udies, suppo s a pa hogenic ole o HCV in
neu opsychia ic and neu ocogni i e diso de s (Monaco e al.,
2015). In a ecen e iew, Ya lo e al. (2017) called his
associa ion be ween HCV, cogni i e impai men , a igue and
dep ession he “Hepa i is C Vi us B ain Synd ome.” This
synd ome is p obably gene a ed by pe iphe al immune esponses
a ec ing he CNS, neu oin lamma ion associa ed wi h CNS HCV
in ec ion, as well as o nega i e li e e en s and o he psychogenic
s esso s (Ya lo e al., 2017).
Fo on e al. (2001) showed e idence ha HCV can c oss
he blood-b ain ba ie and eplica e in he CNS, eme ging
h ough in ec ed monocy es and in ec ing mic oglial cells.
Using p o on magne ic esonance spec oscopy in pa ien s and
con ols, hey ound an inc ease in basal ganglia and whi e
ma e choline/c ea ine a ios in pa ien s, sugges ing an al e ed
me abolism in pa ien s wi h ch onic HCV; hese esul s we e
no explained by hepa ic encephalopa hy o his o y o d ug use
(Fo on e al., 2001).
Neu ocogni i e impai men , one o he mos common
ex ahepa ic mani es a ions o HCV, can lead o sub le changes
in p ocessing speed, memo y, a en ion, a igue, and cogni i e
pe o mance. Up o 50% o HCV-in ec ed pa ien s may de elop
clinical o subclinical mani es a ions o his dys unc ion, and
hese cogni i e de ici s a e independen o he s age o he li e
disease (Low y e al., 2010;Fe i e al., 2016;I iana e al., 2017).
Hilsabeck e al. (2002) ound ha HCV pa ien s expe ience
cogni i e de ici s, especially in a en ion, lea ning, psychomo o
speed, and men al lexibili y. This s udy shows ha main aining
a en ion and concen a ion while pe o ming accu a ely was
he mos di icul ask o non-ci ho ic pa ien s, wi h 50%
aking an abno mally long ime o comple e he ask, 28.9%
making a signi ican numbe o omission e o s, and abou
20% o non-ci ho ic pa ien s pe o ming in he impai ed ange
in ol ing a en ion/concen a ion, isual scanning and acking,
psychomo o speed, and men al lexibili y (Hilsabeck e al., 2002).
The au ho s sugges ha his cogni i e impai men is simila
o ha epo ed in pa ien s wi h a neu ocogni i e diso de
associa ed o o he ch onic illness, such as HIV and AIDS-
ela ed demen ia, and ha hese de ici s a ec QoL and unc ional
capaci y in pa ien s (Hilsabeck e al., 2002).
Rega ding cogni i e and psychia ic dys unc ions, se e al
s udies we e pe o med o assess he impac o HCV in pa ien s,
namely dep ession, anxie y, a igue, a en ion, execu i e unc ion,
and isuospa ial unc ion de ici s (Monaco e al., 2015; Thames
e al., 2015). Cogni i e impai men s we e p e iously hough o
be associa ed wi h he de elopmen o hepa ic encephalopa hy
(Gae a e al., 2013). Howe e , hei p esence was demons a ed in
he absence o ad anced li e disease as well as in he absence o
HIV co-in ec ion, dep ession, o subs ance abuse (Che ne e al.,
2005;Kuhn e al., 2017;Ya lo e al., 2017). Despi e he absence
o hose como bidi ies, de ici s in a en ion, concen a ion,
psychomo o speed, and e bal luency ha e been epo ed
in HCV pa ien s (Weissenbo n e al., 2004;Cli o d e al.,
2009). Findings emain con o e sial and i is unclea i HCV
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Ba ei a e al. Psychosocial, Neu ocogni i e Fac o s and Hepa i is C
e adica ion imp o es HCV-associa ed neu ological comp omise
(Kuhn e al., 2017). Bladowska e al. (2013) in a ollow-up s udy
o e 48 weeks a e he cessa ion o ea men , ound signi ican
imp o emen in a en ion and wo king memo y in pa ien s
who success ully clea ed he i us. This inding sugges s ha
o e ime, he bene i s o HCV clea ance can be mo e ma ked.
Howe e , in o he esea ch p o ocols sus ained i ologic esponse
(SVR) was no ela ed o any imp o emen in neu ocogni i e
pe o mance (Huckans e al., 2015;Low y e al., 2016).
The e o e, he neu ocogni i e p o ile o hese pa ien s be o e
ea men needs o be add essed due o he possible implica ions
on he ea men cou se (e.g., non-adhe ence-like beha io due o
cogni i e abno mali ies). Addi ionally, i is impo an o add ess
o he isk ac o s ha can ha e a nega i e impac on cogni ion.
The high a e o subs ance abuse and he p e alence o psychia ic
diso de s among HCV-in ec ed pa ien s a e impo an ac o s
associa ed wi h cogni i e impai men ha igge poo adhe ence
and ea men e icacy (Wiêdłocha e al., 2017).
Se e al s udies ha e sugges ed ha ea lie ea men is
associa ed wi h imp o emen o he QoL in ch onic HCV pa ien s
(Ma inho and Ba ei a, 2013;Bosca ino e al., 2015;Lucaciu and
Dumi ascu, 2015;Neg o e al., 2015;Chasse e al., 2017;I iana
e al., 2017), highligh ing he impo ance o HCV ea men . In
o de o op imize ea men ou comes, a p e ea men p o ile
helps o iden i y isk ac o s ha can be modi iable be o e and
du ing ea men , such as ea men dis up ion, non-adhe ence,
he isk o ( e)in ec ion and isk o eme gence o dep essi e
diso de s (Basse i e al., 2010).
The p e- s.-pos ea men neu ocogni i e changes ha may
occu among SVR pa ien s equi e u he esea ch o unde s and
he impac o neu oana omical and unc ional changes in HCV
pa ien s be o e, o e he cou se o ea men , and a e success ul
clea ance o he i us.
DISCUSSION AND CONCLUSION
This mini- e iew shows ha pa ien s wi h HCV o en eel
s igma ized and unsuppo ed in hei ca e, ela ionships, and
wo k en i onmen s, while simul aneously coping wi h physical
and psychological symp oms. This syn hesis poin s o a eas whe e
g ea e educa ion, compassion, and pa ien -cen e ed heal hca e
could imp o e he expe ience o people li ing wi h HCV.
In a b oade pe spec i e, and ying o close he loop,
neu ocogni i e impai men can be esponsible o he apy
non-adhe ence in se e al diseases (Rohde e al., 2017;Smi h
e al., 2017) and o losing in e nal esou ces o deal wi h a
ch onic disease (Boehme e al., 2016). Adap i e beha io is
he e o e impai ed, social ne wo ks a e dis up ed and pa ien s’
de ici s in ins umen al daily li e abili ies a e inc eased. These a e
ac o s known o be associa ed o a wo se QoL (Vilhena e al.,
2014), po en ial complica ions in disease e olu ion (Ve e, 2009),
and o e all a wo se p ognosis. Whe he , media ing a iables
in his p ocess include indi idual psychological ai s, nega i e
o posi i e a ec i e s a es, cogni i e impai men , biological
esponses associa ed o mo e pa hogenic i al s ipes, o o he
combina ion o mul iple disease- ac o s, is ye an open deba e.
Howe e , he ele ance o hose psychosocial a iables in ch onic
diseases is nowadays unques ionable (Fa a e al., 2016;Kemp,
2017;McLachlan and Gale, 2018). In wha conce ns wellbeing, all
he desc ibed dimensions may be a ec ed by psychosocial ac o s
and hey can be managed h ough an in eg a ed in e en ion.
Ac ions on p e en ing, iden i ying and ea ing hepa i is C should
be a p io i y and need o be included in local heal h and wellbeing
s a egies in o de o p omo e be e heal h ou comes.
The associa ion be ween neu ocogni i e unc ions,
psychological wellbeing, and ac i i ies o daily li ing among
pa ien s wi h hepa i is C has had li le a en ion. Unde s anding
ac o s, which can impac physical unc ioning and psychological
wellbeing, may ha e an impo an clinical ela ion o imp o ing
ou comes o pa ien s wi h his disease.
T ea men o HCV equi es educa ion e o s o a wide base,
wi h he goal o imp o ing knowledge, and a i udes abou his
disease. These e o s mus include pa ien s and hei amilies,
policy decisions, heal h ca e p o essionals, and socie y as a whole.
A ho ough s udy o HCV-associa ed s igma, clinical, and social
implica ions is essen ial o helping pa ien s o cope wi h he
disease.
In es iga ion suppo s ha HCV expe ience and ea men
adjus men may be acili a ed h ough he use o heo e ical
in o med psychological in e en ions. Conside ing he impac
o HCV in ec ion in pa ien s’ men al heal h and wellbeing,
be o e, and du ing ea men , an in e disciplina y app oach
should be ollowed and encou aged. Besides HCV-associa ed
dep ession, mo e s udies a e needed o cha ac e ize he e en ual
neu ocogni i e side e ec s o he new in e e on- ee egimes and
hei impac on mood como bidi ies.
AUTHOR CONTRIBUTIONS
All au ho s lis ed ha e made a subs an ial, di ec and in ellec ual
con ibu ion o he wo k, and app o ed i o publica ion.
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