Psychological factors associated with NAFLD/NASH- a ......Psychological factors associated with NAFLD/NASH: a systematic review 5083 Inclusion Criteria At least one psychological factor

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Abstract. – OBJECTIVE: Nonalcoholic fat-ty liver disease (NAFLD) represents one of the most common chronic liver diseases world-wide. So far, the pathogenesis of NAFLD and its more severe variant nonalcoholic steatohep-atitis (NASH) is yet unclear, with many mecha-nisms being proposed as possible causes. This article aims to review the psychological factors associated with NAFLD/NASH.

MATERIALS AND METHODS: Three main ca-tegories of factors have been investigated: emo-tional, cognitive and behavioral. Five electronic databases were searched, limited to studies pu-blished in the English language, during the pe-riod 2005-2015: PubMed, Thomson ISI – Web of Science, Scopus, ProQuest, and ScienceDirect.

RESULTS: Results indicated the most relevant emotional factors to be depression and anxiety. The areas of investigation for cognitive func-tioning concern those contents and processes related to the ability to initiate and maintain life-style changes. The most important behavioral factors identified are physical activity, nutrition/food intake and substance consumption: coffee, alcohol, cigarettes.

CONCLUSIONS: Some of the factors identi-fied act as protective factors, other as vulnera-bility factors. NAFLD/NASH may be considered a cognitive-behavioral disease, the most effec-tive management being lifestyle changes, with emphasis on diet and exercise.

Key WordsNonalcoholic fatty liver disease (NAFLD), Nonalco-

holic steatohepatitis (NASH), Cognitive factors, Behav-ioral factors, Emotional factors.

Introduction

Nonalcoholic fatty liver disease (NAFLD) re-presents one of the most common chronic liver diseases worldwide. NAFLD is an umbrella term used to name a condition identified in 1981 in pre-

gnant women1. The term was introduced in 1986 to describe a spectrum of diseases ranging from a simple benign fatty liver (hepatic steatosis) to nonalcoholic steatohepatitis (NASH), to progres-sive fibrosis and cirrhosis2.

Chronologically, the nonalcoholic steatohepa-titis (NASH) was coined before NAFLD, in 1980, by Ludwig et al3. They described the pattern of li-ver injury observed in a group of patients treated at Mayo Clinic. It refers to a condition of fat accu-mulating in the liver, due to causes different from excessive alcohol consumption (less than 20 g per day) or any other specific causes of hepatic stea-tosis3. Most of these patients were obese women, thus associating from the very beginning NASH with one of the most debilitating conditions of the present time-obesity3. Of all the patients affected by NAFLD, only those with histologic evidence of steatohepatitis are shown to progress to fibro-sis or cirrhosis4. Some studies5 show between 10%-29% of patients with NASH will develop cirrhosis within a 10-year period, underlying the importance of prevention and early treatment. The most important histologic feature of NAFLD is the accumulation of triacylglycerols and diacyl-glycerols in hepatocytes6. Visceral fat provides most of the triglycerides leading to steatosis offering a possible explanation for the cases of generally lean individuals, centrally obese, who develop NAFLD7.

Although the world-wide prevalence has not yet been determined, rates of 10-24% were esti-mated in various general populations8. The pre-valence of NAFLD increases significantly, up to 74% in obese individuals8. In the United States alone, this condition represents over 75% of the chronic liver disease1.

NAFLD is reported among all racial and ethnic groups. Hispanics have the highest prevalence of NAFLD, 45%. For the non-Hispanic whites, pre-valence was estimated to be 33%, while for the

European Review for Medical and Pharmacological Sciences 2016; 20: 5081-5097

B. MACAVEI1, A. BABAN1, D.L. DUMITRASCU2

1Department of Psychology, Babes-Bolyai University, Cluj-Napoca, Romania12nd Medical Clinic, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania

Corresponding Author: Adriana Baban, Ph.D; e-mail: [email protected]

Psychological factors associated with NAFLD/NASH: a systematic review

B. Macavei, A. Baban, D.L. Dumitrascu

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African Americans 24%1. In China9, the commu-nity prevalence of nonalcoholic fatty liver disease was estimated at a relatively lower rate of 15%. In India, the prevalence of NAFLD is around 9% to 32% in the general population, with higher preva-lence in overweight or obese individuals10. Women tend to develop the disease later than men (in the sixth decade of life vs. the fourth), the condition being more frequent in male than female1. NAFLD is a disease affecting people regardless of age; it has been reported1 in children as young as 2. So-me studies8 indicate 2.6% of children are affected, with higher rates in case of obese child population ranging from 22.5% to 52.8%.

The pathogenesis of NAFLD is not yet fully clarified. It might be multifactorial, with many mechanisms as possible causes; among the most important are insulin resistance, oxidative stress, apoptosis, and adipokines7,11. Based on available data from clinical, experimental and epidemio-logical studies, there is now a consensus that primary NAFLD is the hepatic manifestation of the metabolic syndrome11,12.

Insulin resistance, mostly in the context of extra weight and obesity, generates higher levels of hepatic free fatty acid (FFA); this condition facilitates the development of NAFLD6. FFA oxidation leads to the generation of toxic reactive oxygen species resulting in hepatic injury and inflammation. As a consequence, the initiation and progression of fibrosis are likely to follow6.

Associated ConditionsNAFLD has been associated with many other

conditions, among them obesity and visceral fat, diabetes mellitus, hyperlipidemia, and hypotha-lamic-pituitary dysfunction8. Some studies show that obese pregnant women can pass on their metabolic phenotype to their children. In turn, early childhood obesity predicts the development of nonalcoholic fatty liver disease later on13. In adolescence, a range of liver problems are as-sociated with greater rates of weight-for-height change between 1-10 years, mediated by concur-rent body fatness14. Other researches underline that overweight and obesity lead to increased quantities of hepatic-free fatty acids, generating an environment appropriate for the development of NAFLD6. As such, the prevalence of NAFLD in obese persons can go as high as 74%8.

An independent risk factor for the develop-ment of NAFLD was identified in dietary fructose6.

Steatosis can also come as a consequence of multiple rare genetic conditions, which influen-

ce the liver processing of nutrients and lipids. Mutations that contribute to either an increase in lipid synthesis/uptake or a decrease in hy-drolysis/export (e.g., glycogen storage diseases, ATGL defects, or very-low-density lipoproteins mutations) were associated with NAFLD15. Some other conditions associated with NAFLD include parental nutrition, acute starvation, abdominal surgery, use of several drugs (e.g. amiodarone, tamoxifen, glucocorticoids, synthetic estrogens, diltiazem, aspirin, methotrexate, highly active antiretroviral therapy), hepatitis C, HIV and me-tabolic disorders16,17.

A complication of hepatic steatosis, the no-nalcoholic steatohepatitis (NASH) is proven to be associated with cardiovascular diseases and malignancy. In a study of biopsy-proven NASH18, the main causes of death in patients were cardio-vascular disease and malignancy. Also, studies19 show both hepatic steatosis and the more aggres-sive NASH are associated with type 2 diabetes mellitus.

Methods

Psychological Risk and Protective factors for NASH/NAFLD

A systematic review was conducted in an attempt to answer the question “Which are the most important psychological factors (emotional, behavioral and cognitive) associated with NASH/NAFLD?”.

Five electronic databases were searched, limi-ted to studies published in the English language, during the period 2005-2015: PubMed, Thomson ISI - Web of Science, Scopus, ProQuest, and ScienceDirect.

The search terms used were nonalcoholic ste-atohepatitis along with each of the following: (1) “psychological risk factors”, (2) “psycholo-gical factors”, (3) “psychological predictors”, (4) “behavioral factors”, (5) “emotional factors”, (6), “affective factors”, (7) “cognitive factors”, (8) “resilience factors”, (9) “anxiety”, (10) “de-pression”.

Studies published in a peer-reviewed journal from January 2005 to December 2015, whi-ch evaluated risk and resilience psychological factors associated with NAFLD/NASH were included in this review. These conditions were selected because of the shared common elemen-ts regarding their biological and psychological mechanisms.


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Inclusion CriteriaAt least one psychological factor associated with

NASH/NAFLD was included in each study co-gnitive, emotional/affective or behavioral. Studies were specifically designed to investigate the asso-ciation of risk and protective factors with NAFLD/NASH manifestations. Studies were clinical trials, single-case experiments, cohort trials, or surveys.

Exclusion CriteriaNon-English language studies were excluded.

Also, studies conducted on animals, and children or adolescents (age <18) were excluded. Studies focusing on treatment or different forms of inter-vention to change factors contributing to the on-set or exacerbation of NAFLD/NASH symptoms

were not included. Also, studies focusing prima-rily on factors other than the psychological ones targeted (e.g., obesity, hypertension, age, low bir-th weight, coronary artery disease, metabolic risk factors, pain, impaired glucose tolerance, type 2 diabetes, cirrhosis) were excluded.

Results

A total of 4583 abstracts were initially identified by using the ten established search combinations in the five databases. Of these abstracts, 107 met the search criteria and were later analyzed about exclusion criteria. In Figure 1, we detail the process by which 29 final articles were selected for analysis.

Figure 1. Articles included and excluded in the final analysis.


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Emotional/Affective FactorsDepression and anxiety were the two emotio-

nal factors mostly investigated in relationship to NAFLD/NASH.

Depression is currently one of the leading causes of death and disability in the general adult population, and expected to become the second leading cause of disability in all age groups by 202020. In a foreword by Deborah Wan, president of World Federation of Mental Health issued for the 20th Anniversary of World Mental Health Day in October 2012 it is specified that unipolar depressive disorders were the third leading cause of the global burden of disease in 2004 and will move into the first place by 203021. It is also the most common mental disorder in patients with chronic conditions22. It is yet unclear if chronic conditions lead to depression, or major depres-sion constitutes a risk factor for chronic illnesses. The relationship could be both ways. However, in an attempt to clarify this issue, Pattern et al23 proved that a set of different conditions characte-rized particularly by pain, inflammation and/or autonomic reactivity (e.g., arthritis, peptic ulcer, migraines) has a higher incidence in people with major depression.

There were several studies discussing the role of depression and anxiety in relationship to NAFLD/NASH, in which clear associations between emotional symptoms and liver disease symptoms could be identified.

Stewart et al24 explored possible associations between anxiety, depression, personality factors, readiness for behavior change and weight outco-mes in 58 overweight or obese participants with NAFLD. Anxiety and depression, as well as cognitive complaints, were considered psycho-logical symptoms and were assessed using the Brief Symptom Inventory. Although mean scores for anxiety, depression and cognitive dysfunction were in the average range, these symptoms were significantly more frequent than in the general population. Also, depression, low conscientiou-sness, and high neuroticism were associated with higher weight at 6-month follow-up.

The study of Youssef et al25 explored the association of depression and anxiety with the severity of histological features of NAFLD in 567 patients. Results indicate that depression is signi-ficantly associated with more severe hepatocyte ballooning in a dose-dependent manner. Patients with subclinical depression had 2.1 times higher likelihood of having more severe hepatocyte bal-looning grade than patients without depressive

symptoms. Also, patients with clinical depres-sion had 3.6 times higher likelihood of having more severe hepatocyte ballooning grade when compared to the non-depressed individuals. In conclusion, there seems to be a dose-dependent association between severity of depressive symp-toms and severity of hepatocyte ballooning. The-se associations were not supported for anxiety symptoms.

Some studies26 suggest emotional problems like anxiety and depression could influence the progression of chronic liver diseases, among whi-ch NAFLD/NASH. Elwing et al26 compared pa-tients diagnosed with nonalcoholic steatohepatitis (NASH), a more severe form of NAFLD, to ma-tched controls without a liver disease in regards to emotional disorders. Major depressive disorder and generalized anxiety disorder diagnoses were established based on the DSM-IV criteria; they preceded the diagnosis of liver disease. The au-thors concluded that major depressive disorder, as well as generalized anxiety disorder, appeared more frequently in patients with NASH and were associated with more advanced liver histological abnormalities.

Also, patients with chronic hepatitis C and NAFLD seem to have a higher prevalence of depression than patients with hepatitis B and the general population27. In this study, depression was self-reported and confirmed by the history of prescription medication. The main factors independently associated with depression in NAFLD were hypertension, smoking, history of lung disease, being female and non-Afri-can-American27.

Depression seems to be associated not just wi-th NAFLD, but also with other liver diseases. The prevalence of depression in hepatitis C patients is known to be high, ranging from 20% to 60%27. In a recent investigation of the relationship betwe-en liver diseases, major depression and suicide attempts, Le Strat et al29 found that participants with a liver disease were 2.2 times more likely to have major depression, after adjustment for a number of socio-demographical, medical and behavioral factors (e.g., age, sex, race, marital status, educational level, past history of cardio-vascular disorder or heart attack, hypertension, arthritis, average volume of alcohol consumed daily and smoking status). Liver diseases were associated with both major depression and suicide attempts among adults in the community29.

Other studies could not find a clear asso-ciation between NAFLD/NASH in particular


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and major depression, although there is a pro-ven pattern of relations between liver diseases and depression. Upon examination of four chronic liver diseases (i.e., chronic hepatitis C, chronic hepatitis B, alcohol-related liver disease, and nonalcoholic fatty liver disease), the authors of a 2013 study30 concluded that chronic hepatitis C alone had a strong asso-ciation with depression.

Another investigation by Surdea-Blaga and Dumitrascu31 provided results indicating there are no differences when comparing the scores of depression, anxiety, or distress in women with NASH and women with viral hepatitis. In this research depression, anxiety and distress scores were not statistically different in patients with NAFLD and normal LST as compared with pa-tients with NASH and elevated LST.

In conclusion, at the moment there are a rela-tively small number of studies investigating the relationship between NAFLD and depression. Results are conflicting and some confounders like obesity and diabetes mellitus may be worth investigating. Also, designing further studies wi-th relevant control groups and more valid forms of measurement for emotional problems might be of help in clarifying the issue.

Concerning the relationship between anxiety and NAFLD, the data collected in several investi-gations indicate it is similar to that found in the case of depression. In the 2013 study by Youssef et al25, subclinical and clinical anxiety was no-ted in 45% and 25% of patients with NAFLD, respectively. Another paper26 reported that ge-neralized anxiety disorder is overrepresented in NASH subjects and is associated with more ad-vanced liver histological abnormalities. The 2011 investigation by Surdea-Blaga and Dumitrascu31 found no differences in anxiety among patients with NAFLD and normal LST and patients with NAFLD and elevated LST as well as patients with viral hepatitis.

Other more specific emotions, like fear of falling, also play a part in the evolution of NAFLD32. Fear of falling highly influences the involvement in physical activity, which is cen-tral to NAFLD management32. Self-efficacy, expressed as confidence to perform, seems to be involved as a possible mechanism underlying the fear of falling.

Although the relationship between liver di-seases and anger received less attention, a stu-dy conducted by the Duke University Medical Center researchers deserves consideration33. The

team found that healthy people prone to anger, hostility and mild to moderate depressive symp-toms produce higher levels of C-reactive protein (CRP), known to promote cardiovascular disease and stroke. CRP is a substance involved in plaque development and plaque’s clogging up of arte-ries, and is produced by the liver in response to inflammation. Moreover, another team of Israeli researchers34 found that elevation of liver enzy-mes correlate with higher CRP concentrations that could be indicative of a worsening of liver disease. Starting from these conclusions, further researches should attempt to investigate the pos-sible role of anger, hostility, and depression as possible contributors to liver inflammation.

In summary, the relationship between NAFLD/NASH and emotional problems like depression and anxiety, in particular, is receiving more and more attention, as some correlation between these conditions begins to emerge. However, results are mixed and further studies might benefit from de-signs specifically elaborated to clarify causality.

Cognitive FactorsSome cognitive factors relevant to patients’

ability to engage in necessary lifestyle changes were also investigated in relationship to NAFLD/NASH.

Frith et al32 assessed two of the cognitive fac-tors relevant to the uptake of physical exercise in patients with NAFLD: confidence to exercise and perceived benefits of exercise. They concluded that confidence to exercise (i.e., the belief one can engage in and complete physical exercises) was significantly lower in NAFLD patients when compared to the primary biliary cirrhosis (PBC) patients and comparable to that of alcoholic li-ver disease (ALD) patients. However, patients in all three groups had similar levels of exercise expectations, thus understanding the benefits of working out. Consequently, although the NAFLD patients understand the importance to exercise, they seem to lack the confidence to engage in physical activity.

In individuals with NAFLD, ratings of percei-ved exertion (RPE) were related to the level of physical activity in adulthood35. Ratings of per-ceived exertion refer to perception of effort and are defined by sensations of effort, constraints, discomfort and fatigue one feels when engaging in physical activity. The way people assess their feelings of physical stress, effort and fatigue while doing exercises influences further involve-ment in such activities and regulation of effort.


5086

Therefore, in patients with NAFLD, the way they perceive exertion depends on the glucose level, as well as self-reported physical activity. As such, because RPE can stimulate or deter a person to engage in exercises, it could be used to prescribe appropriate physical activities for patients with NAFLD.

Stewart et al24 brought further evidence suggesting that overweight/obese NAFLD pa-tients have a readiness to change consistent mostly with the pre-contemplation and con-templation stages of the Stages of Change Model36. Only about 10% of their 58 patients sample were either preparing to or were acti-vely making lifestyle changes, an important requirement for the management of NAFLD. These conclusions were further supported by the results of a 2013 study by Centis et al37. In a sample of 138 NAFLD patients, the authors found that in case of physical activity about 50% of subjects could be classified in either pre-contemplation or contemplation stages. In case of diet, no subjects were classified in the pre-contemplation phase, 36% were in the contemplation phase, while 64% were distri-buted in determination to change, actions for changing and changed maintenance phases. Such findings suggest that, for reasons that could involve various thoughts and cognitions (i.e., information scarcity, personal beliefs, low self-efficacy beliefs, etc.) NAFLD patien-ts have little motivation for changing their diet or engaging in physical activity.

Some studies found cognitive dysfunction (e.g., memory impairment, attention deficit, etc.) to be significantly more frequent in the overwei-ght/obese NAFLD population than in the general population24. However, in a study by Felipo et al38 only a small number of patients with NASH, a more advanced form of NAFLD, could be clas-sified as having mild cognitive impairment asso-ciated with hyperammonemia and inflammation. None of the patients with NAFLD showed any cognitive impairment. Further data are needed to clarify whether NAFLD patients are at risk for cognitive dysfunction.

In summary, for NAFLD patients, the most relevant areas of investigation for cognitive fun-ctioning concern those contents and processes related to the ability to initiate and maintain lifestyle changes. The cognitive mechanisms underlying dietary behaviors and engagement in physical activity are some of the most important targets for further investigation.

Behavioral Factors

Physical ActivityThe level of physical activity seems to be af-

fected in patients with NAFLD. Elliott et al39 as-sessed the extent of impairment in daily activity patients diagnosed with NAFLD and ALD have when compared with healthy controls. Results in-dicate all liver disease patients experience signi-ficant difficulties in their daily activities, across eight domains of physical functioning: dressing, arising, eating, walking, hygiene, reach, grip, and activity. In case of NAFLD patients, age, fatigue, autonomic dysfunction, and cognitive difficulty are associated with worsening functional difficul-ty. The impairment appears to persist in time, and was observed over a 3 year period in this study.

Koehler et al40 found that total physical acti-vity was associated with NAFLD in an elderly population. Also, Oni et al41 indicated that people with higher levels of physical activity had lower odds of having NAFLD. The association was maintained independentely of obesity and the metabolic syndrome.

Although the overall level of physical activity seems to be important in NAFLD, Kistler et al42 brought evidence supporting that it is the inten-sity of physical exercise that is associated with the severity of NAFLD. The authors suggest that intensity of exercise may be more important than duration or total volume. Results presented in this particular study indicate that neither moderate intensity exercise, nor total exercise per week was associated with NASH or stage of fibroses. It ap-pears that vigorous physical exercise is beneficial to NAFLD to a much higher extent than physical activity in general.

Conversely, reduced physical activity seems to impact NAFLD in a negative manner. Hua et al43 found that elderly day nappers had a significantly higher prevalence of NAFLD. Longer habitual day napping was associated in a dose-dependent manner with NAFLD.

In summary, intense physical exercise may act as a protective factor against the debut and aggravation of NAFLD symptoms.

Food Intake/DietImproper food intake, low on nutrients and

high in saturated fat and carbohydrates seems to be a significant risk factor for NAFLD/NASH. Some investigations have attempted to assess the impact of different foods and nutrients on liver functioning.


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Yu et al44 explored the role of dietary choline – found in eggs, soy foods, red meat, fish and ve-getables – in relation to NAFLD. Lack of choline is known to stimulate liver fat accumulation. Conversely, higher dietary choline intake seems to be associated with lower risk of NAFLD in normal-weight Chinese women.

Zelber-Sagi et al45 concluded that the inta-ke of soft drinks and meat was significantly associated with an increased risk for NAFLD. Also, the NAFLD patients appear to have a tendency to consume lower quantities of fish rich in omega-3. Body mass index (BMI), waist circumference and percent dietary fat intake proved to be independent nutritional risk factors for NAFLD46. Most NAFLD pa-tients presented a significantly high intake of meats, fats, sugars, legumes (beans), and vegetables and a low consumption of cereals, fruits, and dairy products compared with the recommendations47. Low nutrient food intake seems to be relatively common in NAFLD patients.

Kim et al48, indicated that NAFLD patien-ts consumed more low-nutrient food, and more high-sodium food than HBV (hepatitis B virus) patients. Also, NAFLD patients ingested fewer calories from fruits than chronic viral hepatitis patients.

In women, vitamin K and vegetable intakes were shown to have a beneficial effect on lowe-ring the NAFLD risk. In men, low intakes of vi-tamin C, Vitamin K, folate, omega-3 fatty acids, nuts and seeds were associated with a high risk for developing NAFLD49.

Musso et al50 showed that subjects with NAFLD had lower vitamins A and E intakes than control subjects. Nitrotyrosine and adipo-nectin concentrations and vitamin A intake in-dependently predicted alanine aminotransferase concentrations in NAFLD patients and liver hi-stology in a subgroup of biopsy-proven NASH subjects.

According to Kang et al51, in NAFLD patients, the metabolic syndrome is associated with more carbohydrate and less fat intake and greater hi-stological severity.

In summary, in the development of NAFLD and the severity of symptoms, poor nutrition seems to play a central role and needs further investigation.

Substance Consumption: Coffee, Alcohol, Smoking

Some pretty usual lifestyle habits seem to develop as protective factors against the onset of NAFLD. As such, greater consumption of coffee has been associated with a significantly reduced prevalence of cirrhosis in patients with chronic liver disease. Walton et al52 indicated that patients with cirrhosis drank significantly less coffee than those without cirrhosis. Moreover, some studies identified an increased activity of the autophagy-lysosomal pathways in mice fed caffeine, inferring a biochemical explanation for the protective role of caffeine1.

In regards to coffee consumption, it is yet unclear if the beneficial effect is due to coffee in itself or just the caffeine component.

Alcohol represents another frequently used substance that has been investigated in relation to NAFLD. Kwon et al53 concluded that patients who used alcohol moderately had a decrease in the histological severity of NAFLD. Other studies have shown that moderate wine drinking (i.e., one glass of wine per day) was correlated with a decreased prevalence of suspected NAFLD54. When comparing nondrinkers and moderate drinkers with NAFLD, data show lower rates of steatohepatitis in the moderate drinkers55.

In summary, moderate alcohol consumption (especially wine) may have favorable effects on patients with NAFLD or at risk for NAFLD.

Contrary to the effect of coffee consumption and moderate alcohol drinking, smoking seems to have a detrimental effect on the evolution of NAFLD. Not only does active smoking contri-bute to the exacerbation of symptoms, but also passive smoking appears to negatively influence liver functioning. Liu et al56 showed that passive smoking during childhood and adulthood was associated with a 25% increase in the risk for NAFLD. The combination of active smoking and body mass index (BMI) was also associated with a high risk for NAFLD. In a 2012 study, Koehler et al40 proved that pack years of smoking, as well as other variables, were associated with NAFLD. Smoking also influences the severity of NAFLD. A study by Zein et al57 indicated smoking history to be associated with advanced liver fibrosis in NAFLD patients.

In summary, cigarette smoking may aggravate fatty liver.


5088

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gica

l fea

ture

s

i

n 14

%, s

ubcl

inic

al an

xiet

y o

f NA

FLD

.

w

as n

oted

in 4

5% a

nd

c

linic

al an

xiet

y w

as n

oted

in

25%

of s

ubje

cts.

S2

1.

Wei

nste

in A

A,

878

patie

nts w

ith c

hron

ic

Com

paris

ons w

ere

Emot

iona

l: de

pres

sion

Pa

tient

s with

NA

FLD

and

hep

atiti

s C h

ave

a hi

gher

pre

vale

nce

e

t al (

2011

) l

iver

dis

ease

. 207

of a

ll

con

duct

ed u

sing

the

of d

epre

ssio

n th

an h

epat

itis B

pat

ient

s and

the g

ener

al p

opul

atio

n.

p

atie

nts (

23.6

%) w

ere

M

ann-

Whi

tney

test

and

For N

AFL

D, i

ndep

ende

nt p

redi

ctor

s of d

epre

ssio

n w

ere

the

dia

gose

d w

ith d

epre

ssio

n

Kru

skal

-Wal

lis te

st.

p

rese

nce o

f hyp

erte

nsio

n, sm

okin

g, h

istor

y of

lung

dise

ase,

(N

AFL

D 2

7.2%

, hep

atiti

s C

Reg

ress

ion

mod

els w

ere

b

eing

fem

ale

and

non

–Afr

ican

- Am

eric

an.

2

9.8%

, hep

atiti

s B 3

.7%

). u

sed

to id

entif

y

ind

epen

dent

pre

dict

ors

o

f dep

ress

ion.

Table

I.

Stud

ies s

elec

ted

to b

e re

view

ed.

Con

tinue

d


5089

Stu

dy

Au

thors

, Sa

mple

char

acte

rist

ics

Met

hod

Psy

cholo

gic

al

Res

ult

s

ye

ar

(N

o, ag

e, g

end

er,

fa

ctors

d

iag

nosi

s)

id

enti

fied

S2

2.

Surd

ea-

63 p

atie

nts w

ith N

AFL

D,

Gro

ups c

ompa

red

usin

g Em

otio

nal:

depr

essi

on,

No

diff

eren

ces i

n an

xiet

y, d

epre

ssio

n or

dis

tress

scor

es c

ould

be

B

laga

T a

nd

38

of th

em fe

mal

e.

AN

OVA

, Man

n-W

hitn

ey

anx

iety

f

ound

bet

wee

n fe

mal

es w

ith N

AFL

D a

nd fe

mal

es w

ith v

iral

D

umitr

ascu

D

The

dia

gnos

is o

f liv

er

(ba

sed

on d

ata

h

epat

itis.

(

2011

) s

teat

osis

was

est

ablis

hed

dis

trib

utio

n).

N

o re

latio

n co

uld

be su

ppor

ted

betw

een

NA

FLD

and

dep

ress

ion

bas

ed o

n ab

dom

inal

C

orre

latio

ns u

sing

Pea

rson

o

r anx

iety

.

u

ltras

ound

and

the

aspe

ct

and

Spe

arm

an c

oeffi

cien

ts.

of l

iver

par

ench

yma.

S24.

Fr

ith J,

23

0 no

n-al

coho

lic fa

tty

Coh

ort s

tudy

. Thr

ee

Cog

nitiv

e: c

onfid

ence

U

nder

stan

ding

the

bene

fits o

f phy

sica

l act

ivity

was

sim

ilar i

n al

l

et a

l (20

10)

liv

er d

isea

se –

NA

FLD

, d

iffer

ent g

roup

s (N

AFL

D,

to

exer

cise

, t

hree

gro

ups.

Con

fiden

ce to

exe

rcis

e w

as si

gnifi

cant

ly lo

wer

in

1

10 a

lcoh

olic

live

r dis

ease

A

LD, P

BC

) wer

e

und

erst

andi

ng th

e t

he N

AFL

D g

roup

. Fea

r of f

allin

g w

as si

mila

r in

the

NA

FLD

– A

LD a

nd 9

7 pr

imar

y

com

pare

d in

rega

rds t

o b

enefi

ts o

f exe

rcis

e a

nd P

BC

gro

ups,

and

high

er in

the

ALD

gro

up.

bili

ary

cirr

hosi

s – P

BC

f

acto

rs p

erta

inin

g to

Em

otio

nal:

fear

A

lthou

gh th

ey u

nder

stan

d th

e be

nefit

s of p

erfo

rmin

g ph

ysic

al

sub

ject

s wer

e in

clud

ed.

eng

agem

ent i

n ph

ysic

al

of f

allin

g a

ctiv

ities

, pat

ient

s with

NA

FLD

lack

the

confi

denc

e ne

cess

ary

e

xerc

ise

(lack

of

a

nd a

re a

frai

d of

falli

ng.

c

onfid

ence

, poo

r

In N

AFL

D, f

ear o

f fal

ling

was

inde

pend

ently

ass

ocia

ted

with

und

erst

andi

ng o

f the

inc

reas

ing

diffi

culty

eng

agin

g in

phy

sica

l act

ivity

.

ben

efits

of e

xerc

isin

g,

B

oth

fear

of f

allin

g an

d co

nfide

nce

are

mod

ifiab

le th

roug

h

fea

r of f

allin

g).

p

sych

olog

ical

inte

rven

tion.

S28

. El

win

g JE

, 36

non

alco

holic

stea

to-

A m

ultiv

aria

te m

odel

Em

otio

nal:

anxi

ety

Maj

or d

epre

ssiv

e di

sord

er a

nd g

ener

aliz

ed a

nxie

ty d

isor

der a

re

et a

l (20

06)

hep

atiti

s (N

ASH

) pat

ient

s i

ncor

pora

ting

a nu

mbe

r a

nd d

epre

ssio

n m

ore

freq

uent

in N

ASH

subj

ects

and

are

ass

ocia

ted

with

mor

e

a

nd 3

6 m

atch

ed c

ontro

ls

of p

oten

tial r

isk

fact

ors

a

dvan

ced

liver

his

tolo

gica

l abn

orm

aliti

es.

wer

e us

ed.

for

NA

SH w

as u

sed

to

a

sses

s ind

epen

dent

eff

ects

of m

ajor

dep

ress

ive

d

isor

der a

nd g

ener

aliz

ed

a

nxie

ty d

isor

der o

n

sev

erity

of h

isto

logi

cal

fi

ndin

gs.

C

ogni

tive

fact

ors

S

2.

Wei

nste

in A

A,

Con

veni

ence

sam

ple

of 5

1 O

bser

vatio

nal a

naly

tical

C

ogni

tive:

per

cept

ion

In in

divi

dual

s with

NA

FLD

, rat

ings

of p

erce

ived

exe

rtio

n (R

PE)

e

t al (

2016

) s

ubje

cts d

iagn

osed

with

s

tudy

. Spe

arm

an ra

nk su

m

of e

ffor

t dur

ing

w

ere

rela

ted

to a

met

abol

ic fa

ctor

(fas

ting

gluc

ose

leve

l), a

nd a

N

AFL

D o

r Chr

onic

c

orre

latio

ns w

ere

p

hysi

cal a

ctiv

ity

life

styl

e fa

ctor

(lev

el o

f phy

sica

l act

ivity

in a

dulth

ood)

. Rat

ings

h

epat

itis C

, age

51.

1 ±

8.8

p

erfo

rmed

. Gro

ups w

ere

o

f per

ceiv

ed e

xert

ion

refe

r to

perc

eptio

n of

eff

ort,

whi

ch is

a

yea

rs, 3

5% fe

mal

e.

com

pare

d us

ing

anal

ysis

pow

erfu

l reg

ulat

or o

f eff

ort.

o

f var

ianc

e.

Table

I (

Con

t.).

Stu

dies

sele

cted

to b

e re

view

ed.

Con

tinue

d


5090

Stu

dy

Au

thors

, Sa

mple

char

acte

rist

ics

Met

hod

Psy

cholo

gic

al

Res

ult

s

ye

ar

(N

o, ag

e, g

end

er,

fa

ctors

d

iag

nosi

s)

id

enti

fied

S3

. St

ewar

t KE,

58

ove

rwei

ght/o

bese

A

ssoc

iatio

ns b

etw

een

Cog

nitiv

e: re

adin

ess

Dep

ress

ion,

low

con

scie

ntio

usne

ss, a

nd h

igh

neur

otic

ism

wer

e

et a

l (20

15)

par

ticip

ants

with

NA

FLD

. d

epre

ssio

n, a

nxie

ty,

for

beh

avio

ur c

hang

e,

ass

ocia

ted

with

hig

her w

eigh

t at 6

-mon

th fo

llow

-up.

Of a

ll th

e

per

sona

lity

fact

ors

cog

nitiv

e dy

sfun

ctio

n p

atie

nts,

only

10.

4% w

ere

activ

ely

wor

king

on

or p

repa

ring

to

(ex

., low

cons

cient

ious

ness

, Em

otio

nal:

depr

essi

on,

cha

nge,

alth

ough

all

rece

ived

nut

ritio

nal e

duca

tion

and

n

euro

ticis

m),

read

ines

s a

nxie

ty

gui

danc

e. R

eadi

ness

for c

hang

e w

as n

ot fo

und

to p

redi

ct

f

or b

ehav

ior c

hang

e an

d

s

ubse

quen

t cha

nge

in w

eigh

t.

wei

ght o

utco

mes

in

Co

gniti

ve d

ysfu

nctio

n sy

mpt

oms (

e.g., m

emor

y pr

oble

ms,

atte

ntio

n

NA

FLD

pat

ient

s wer

e

pro

blem

s) w

ere

signi

fican

tly m

ore

freq

uent

in th

e N

AFL

D

e

xplo

red.

sam

ple

than

in th

e ge

nera

l pop

ulat

ion.

C

ompa

red

to th

e ge

nera

l pop

ulat

ion,

dep

ress

ion

and

cogn

itive

dys

func

tion

in p

artic

ular

wer

e sig

nific

antly

mor

e fr

eque

nt in

the

NA

FLD

sam

ple.

S1

3.

Cen

tis E

, 13

8 N

AFL

D p

atie

nts

Logi

stic

regr

essi

on

Cog

nitiv

e: st

age

of

Phys

ical

act

ivity

– 5

0% w

ere c

lass

ified

in e

ither

pre

-con

tem

plat

ion

e

t al (

2013

) (

73%

mal

e, a

ge 1

9-73

). a

naly

sis

cha

nge,

mot

ivat

ion

or c

onte

mpl

atio

n st

ages

.

D

iagn

osis

con

firm

ed b

y

Die

t – 0

% w

ere

clas

sifie

d in

the

pre-

cont

empl

atio

n ph

ase,

36%

liv

er b

iops

y in

64

case

s

w

ere

in th

e co

ntem

plat

ion

phas

e. 6

4% w

ere

dist

ribut

ed in

(

stea

tohe

patit

is 4

7%)

det

erm

inat

ion,

act

ion

and

mai

nten

ance

pha

ses.

NA

FLD

p

atie

nts h

ave

little

read

ines

s to

lifes

tyle

cha

nges

and

mot

ivat

ion

w

ith re

gard

to d

iet a

nd p

artic

ular

ly p

hysi

cal a

ctiv

ity.

S1

5.

Felip

o V,

29

pat

ient

s with

sim

ple

Gro

ups c

ompa

red

usin

g C

ogni

tive:

cog

nitiv

e Fi

ve o

ut o

f 11

NA

SH p

atie

nts,

with

out l

iver

cir

rhos

is, w

ere

e

t al (

2012

) s

teat

osis

(NA

FLD

) A

NO

VA. C

orre

latio

n d

efici

ts/im

pair

men

t

cla

ssifi

ed a

s hav

ing

mild

cog

nitiv

e im

pair

men

t ass

ocia

ted

with

and

11

with

stea

tohe

patit

is

anal

ysis

was

per

form

ed.

h

yper

amm

onem

ia a

nd in

flam

mat

ion.

(N

ASH

). A

ll N

ASH

N

one

of th

e pa

tient

s with

NA

FLD

show

ed c

ogni

tive

impa

irm

ent.

pat

ient

s pre

sent

ed

hep

atic

fibr

osis

.

S

24.

Frith

J,

230

non-

alco

holic

fatty

C

ohor

t stu

dy. T

hree

C

ogni

tive:

con

fiden

ce

Und

erst

andi

ng th

e be

nefit

s of p

hysi

cal a

ctiv

ity w

as si

mila

r in

e

t al (

2010

) l

iver

dis

ease

– N

AFL

D,

diff

eren

t gro

ups (

NA

FLD

, t

o ex

erci

se,

all

thre

e gr

oups

. Con

fiden

ce to

exe

rcis

e w

as si

gnifi

cant

ly lo

wer

110

alc

ohol

ic li

ver d

isea

se

ALD

, PB

C) w

ere

u

nder

stan

ding

i

n th

e N

AFL

D g

roup

. Fea

r of f

allin

g w

as si

mila

r in

the

NA

FLD

– A

LD a

nd 9

7 pr

imar

y

com

pare

d in

rega

rds t

o

the

ben

efits

a

nd P

BC

gro

ups,

and

high

er in

the

ALD

gro

up.

bili

ary

cirr

hosi

s PB

C

fac

tors

per

tain

ing

to

of e

xerc

ise

Alth

ough

they

und

erst

and

the

bene

fits o

f per

form

ing

phys

ical

sub

ject

s wer

e in

clud

ed.

eng

agem

ent i

n ph

ysic

al

Emot

iona

l: a

ctiv

ities

, pat

ient

s with

NA

FLD

lack

the

confi

denc

e ne

cess

ary

e

xerc

ise

(lack

of

fea

r of f

allin

g a

nd a

re a

frai

d of

falli

ng.

c

onfid

ence

, poo

r

In N

AFL

D, f

ear o

f fal

ling

was

inde

pend

ently

ass

ocia

ted

with

u

nder

stan

ding

of t

he

i

ncre

asin

g di

fficu

lty e

ngag

ing

in p

hysi

cal a

ctiv

ity.

b

enefi

ts o

f exe

rcis

ing,

Bot

h fe

ar o

f fal

ling

and

confi

denc

e ar

e m

odifi

able

thro

ugh

f

ear o

f fal

ling)

.

psy

chol

ogic

al in

terv

entio

n.

Table

I (

Con

t.).

Stu

dies

sele

cted

to b

e re

view

ed.

Con

tinue

d


5091

Stu

dy

Au

thors

, Sa

mple

char

acte

rist

ics

Met

hod

Psy

cholo

gic

al

Res

ult

s

ye

ar

(N

o, ag

e, g

end

er,

fa

ctors

d

iag

nosi

s)

id

enti

fied

Beh

avio

ral f

acto

rs –

Phy

sica

l act

ivity

S1

. O

ni E

T,

5,74

3 he

alth

y B

razi

lian

Mul

tivar

iate

logi

stic

B

ehav

iora

l: ph

ysic

al

NA

FLD

pre

vale

nce

was

low

er a

t hig

her l

evel

s of r

epor

ted

e

t al (

2015

) s

ubje

cts,

43 ±

10

year

s old

, re

gres

sion

was

use

d a

ctiv

ity

phy

sica

l act

ivity

. Sub

ject

s with

hig

h ph

ysic

al a

ctiv

ity h

ad lo

wer

79%

men

. NA

FLD

was

t

o ev

alua

te a

ssoc

iatio

n

o

dds o

f hav

ing

NA

FLD

. The

ass

ocia

tion

was

mai

ntai

ned

diag

nose

d usin

g ultr

asou

nds.

bet

wee

n N

AFL

D, p

hysic

al

i

ndep

ende

nt o

f obe

sity

and

met

abol

ic sy

ndro

me.

I

n the

tota

l stu

dy p

opul

ation

, a

ctiv

ity a

nd o

ther

risk

NA

FLD

pre

vale

nce

was

f

acto

rs (o

besit

y, m

etab

olic

3

6% (2

,075

subj

ects)

. s

yndr

ome)

.

S7

. H

ua Q

, O

f 6,9

98 p

artic

ipan

ts,

Cro

ss-s

ectio

nal s

tudi

es o

f B

ehav

iora

l: ha

bitu

al

Day

-nap

pers

wer

e fou

nd to

hav

e a si

gnifi

cant

ly h

ighe

r pre

vale

nce

e

t al (

2014

) a

ged

40-7

5 ye

ars,

6,43

8

the

com

mun

ity p

opul

atio

n

day

nap

ping

o

f NA

FLD

. Lon

ger d

ay n

appi

ng w

as a

ssoc

iate

d in

a d

ose-

elig

ible

par

ticip

ants

wer

e

in C

hina

.

dep

ende

nt m

anne

r with

NA

FLD

.

i

nclu

ded.

A

ssoc

iatio

n be

twee

n th

e

It

appe

ars t

hat i

nflam

mat

ory

cyto

kine

s may

be

a lin

k be

twee

n

dur

atio

n of

hab

itual

day

day

nap

ping

and

NA

FLD

.

nap

ping

and

NA

FLD

in

a

n el

derly

pop

ulat

ion.

Lo

gist

ic re

gres

sion

mod

els

wer

e us

ed.

S1

2.

Ellio

tt C

, 22

4 no

n-al

coho

lic fa

tty

Gro

ups w

ere

com

pare

d B

ehav

iora

l: fu

nctio

nal

Peop

le d

iagn

osed

with

NA

FLD

and

ALD

exp

erie

nce

signi

fican

t

et a

l (20

13)

liv

er d

isea

se (N

AFL

D),

u

sing

anal

ysis

of v

aria

nce,

im

pair

men

t d

iffic

ultie

s in

thei

r dai

ly a

ctiv

ities

whe

n co

mpa

red

with

nor

mal

107

alc

ohol

ic li

ver

and

the

Kru

skal

-Wal

lis

c

ontro

ls. F

unct

iona

l im

pair

men

t app

ears

to p

ersi

st o

ver t

ime

dis

ease

(ALD

) and

100

t

est.

Mul

tiple

line

ar

(

eval

uate

d ov

er a

3 y

ear p

erio

d).

con

trols

wer

e in

clud

ed.

reg

ress

ion

was

als

o

45%

(101

) of t

he N

AFL

D

per

form

ed to

det

erm

ine

pat

ient

s wer

e w

omen

t

he a

ssoc

iatio

n be

twee

n

(

age

59 ±

13)

. f

unct

iona

l im

pair

men

t

a

nd d

isea

se se

verit

y.

S1

7.

Koe

hler

EM

, 2,

811

part

icip

ants

, mea

n

Logi

stic

regr

essi

on

Beh

avio

ral:

smok

ing

Tota

l phy

sica

l act

ivity

, pac

k ye

ars o

f sm

okin

g, a

ge, a

s wel

l as

e

t al (

2012

) a

ge 7

6.4

± 6.

0 ye

ars.

ana

lysi

s was

use

d to

h

abits

, phy

sica

l o

ther

var

iabl

es w

ere

asso

ciat

ed w

ith N

AFL

D.

Pre

vale

nce

of N

AFL

D

ass

ess a

ssoc

iatio

ns

act

ivity

Th

e pr

eval

ence

of N

AFL

D d

ecre

ases

with

adv

anci

ng a

ge in

the

was

35.

1%.

bet

wee

n co

-var

iabl

es

e

lder

ly.

a

nd se

verit

y of

NA

FLD

.

S19.

K

istle

r KD

, 81

3 ad

ults

, 302

mal

es a

nd

Ret

rosp

ectiv

e an

alys

is o

n B

ehav

iora

l: ph

ysic

al

Nei

ther

mod

erat

e in

tens

ity e

xerc

ise,

nor

tota

l exe

rcis

e pe

r wee

k

et a

l (20

11)

511

fem

ales

with

bio

psy-

d

ata

was

con

duct

ed.

act

ivity

was

ass

ocia

ted

with

NA

SH o

r sta

ge o

f fibr

oses

.

p

rove

n N

AFL

D w

ere

G

roup

s wer

e co

mpa

red

D

ata

supp

ort a

n as

soci

atio

n of

vig

orou

s phy

sica

l exe

rcis

e w

ith

i

nclu

ded.

Mea

n ag

e 48

. u

sing

ana

lysi

s of v

aria

nce,

t

he se

verit

y of

NA

FLD

. Res

ults

sugg

est i

nten

sity

of e

xerc

ise

K

rusk

al-W

allis

test

, and

may

be

mor

e im

port

ant t

han

dura

tion

or to

tal v

olum

e.

Man

n-W

hitn

ey te

st.

M

ultin

omia

l log

istic

reg

ress

ion

was

als

o us

ed.

Table

I.

Stud

ies s

elec

ted

to b

e re

view

ed.

Con

tinue

d


5092

Stu

dy

Au

thors

, Sa

mple

char

acte

rist

ics

Met

hod

Psy

cholo

gic

al

Res

ult

s

ye

ar

(N

o, ag

e, g

end

er,

fa

ctors

d

iag

nosi

s)

id

enti

fied

S2

9.

Kan

g H

, 91

pat

ient

s with

NA

FLD

, Pa

tient

s with

met

abol

ic

Beh

avio

ral:

alim

enta

ry P

atie

nts w

ith m

etab

olic

synd

rom

e co

nsum

ed m

ore

carb

ohyd

rate

s

et a

l (20

06)

31

patie

nts (

34%

) had

s

yndr

ome

wer

e co

mpa

red

hab

its, f

ood

inta

ke

and

less

fat c

ompa

red

with

thos

e w

ithou

t met

abol

ic sy

ndro

me.

met

abol

ic sy

ndro

me.

w

ith th

ose

with

out

Beh

avio

ral:

phys

ical

To

tal d

aily

cal

orie

s, pr

otei

n co

nsum

ptio

n, a

nd p

hysi

cal a

ctiv

ity

met

abol

ic sy

ndro

me.

a

ctiv

ity

wer

e si

mila

r for

the

two

grou

ps. M

etab

olic

synd

rom

e in

pat

ient

s

The

con

trib

utio

n of

with

NA

FLD

is a

ssoc

iate

d w

ith m

ore

carb

ohyd

rate

and

less

fat

d

iffer

ent f

acto

rs (e

.g.,

int

ake

and

grea

ter h

isto

logi

c se

verit

y.

die

tary

com

posi

tion,

phy

sica

l act

ivity

) to

N

AFL

D se

verit

y w

as

als

o es

timat

ed.

B

ehav

iora

l fac

tors

– F

ood

inta

ke/d

iet

S5

. Y

u D

, 56

,195

Chi

nese

wom

en a

nd T

he a

ssoc

iatio

n be

twee

n B

ehav

iora

l: al

imen

tary

Hig

her d

ieta

ry c

holin

e in

take

cou

ld b

e as

soci

ated

with

low

er ri

sk

et a

l (20

14)

men

, 40-

75 y

ears

of a

ge.

cho

line

inta

ke a

nd

hab

its, f

ood

inta

ke

of N

AFL

D in

nor

mal

-wei

ght C

hine

se w

omen

.

N

AFL

D w

as a

sses

sed

by

NA

FLD

was

exp

lore

d.

s

elf-

repo

rt of

a p

hysi

cian

St

ratifi

ed a

naly

sis

dia

gnos

is.

sug

gest

ed a

pot

entia

l

eff

ect m

odifi

catio

n by

o

besi

ty st

atus

in w

omen

.

S6.

Han

JM

, 34

8 K

orea

n ad

ult s

ubje

cts

The

asso

ciat

ion

betw

een

Beh

avio

ral:

alim

enta

ry I

n w

omen

, vita

min

K a

nd v

eget

able

inta

kes w

ere

show

n to

hav

e

et a

l (20

14)

par

ticip

ated

. NA

FLD

was

se

vera

l ris

k fa

ctor

s h

abits

, foo

d in

take

a

ben

efici

al e

ffec

t on

low

erin

g th

e N

AFL

D ri

sk

dia

gnos

ed b

y ul

tras

ound

. (

indi

vidu

al n

utrie

nts

In

men

, low

inta

kes o

f vita

min

C, V

itam

in K

, fol

ate,

om

ega-

3

or w

hole

food

gro

ups)

fat

ty a

cids

, nut

s and

seed

s wer

e as

soci

ated

with

a h

igh

risk

for

a

nd N

AFL

D w

as

d

evel

opin

g N

AFL

D

e

xplo

red.

S9.

Mar

inho

96

non

-alc

ohol

ic fa

tty

Cos

s-se

ctio

nal s

tudy

; B

ehav

iora

l: al

imen

tary

Mos

t pat

ient

s exc

eede

d th

e re

com

men

datio

ns fo

r ene

rgy

inta

ke

Fer

olla

S,

liv

er d

isea

se p

atie

nts.

gro

ups c

ompa

red

with

h

abits

, foo

d in

take

a

nd sa

tura

ted

fat.

e

t al (

2013

) M

edia

n pa

tient

age

53

t

-test

and

Man

n-W

hitn

ey

Th

e pa

tient

s pre

sent

ed a

sign

ifica

ntly

hig

h in

take

of m

eats

, fat

s,

y

ears

. 77%

of s

ubje

cts

U te

st. C

hi-s

quar

e te

st

s

ugar

s, le

gum

es (b

eans

), an

d ve

geta

bles

and

a lo

w

wer

e w

omen

. 67.7

%

or F

ishe

r’s e

xact

test

wer

e

con

sum

ptio

n ce

real

s, fr

uits

, and

dai

ry p

rodu

cts c

ompa

red

of p

artic

ipan

ts w

ere

obes

e.

used

to c

ompa

re p

ropo

rtio

ns.

with

the

reco

mm

enda

tions

.

A

ll pa

tient

s und

erw

ent

The

poss

ible

role

of n

utrie

nt d

efici

enci

es in

the

deve

lopm

ent o

f

a

bdom

inal

ultr

asou

nd,

N

AFL

D n

eeds

furt

her i

nves

tigat

ion.

bio

chem

ical

test

s,

d

ieta

ry e

valu

atio

ns, f

ood

int

ake,

ant

hrop

omet

ric

e

valu

atio

ns.

Table

I (

Con

t.).

Stu

dies

sele

cted

to b

e re

view

ed.

Con

tinue

d


5093

Stu

dy

Au

thors

, Sa

mple

char

acte

rist

ics

Met

hod

Psy

cholo

gic

al

Res

ult

s

ye

ar

(N

o, ag

e, g

end

er,

fa

ctors

d

iag

nosi

s)

id

enti

fied

S1

8.

Sath

iara

j E,

98 su

bjec

ts w

ith st

eato

sis

Mul

tiple

logi

stic r

egre

ssio

n B

ehav

iora

l: al

imen

tary

BM

I, w

aist

circ

umfe

renc

e an

d pe

rcen

t die

tary

fat i

ntak

e pr

oved

e

t al (

2011

) a

nd 1

02 c

ontro

ls w

ere

a

naly

sis w

as p

erfo

rmed

h

abits

, foo

d in

take

t

o be

inde

pend

ent n

utrit

iona

l ris

k fa

ctor

s for

NA

FLD

.

inc

lude

d. P

reva

lenc

e of

t

o pr

edic

t the

die

tary

risk

m

etab

olic

synd

rom

e w

as

fac

tors

in N

AFL

D

4

4.9%

am

ong

NA

FLD

c

ases

and

25.

5% a

mon

g

c

ontro

ls.

S23.

K

im C

H,

233

subj

ects

, age

52.

5 ±

NA

FLD

pat

ient

s wer

e B

ehav

iora

l: al

imen

tary

NA

FLD

and

HC

V p

atie

nts c

onsu

med

mor

e hi

gh-fa

t mea

t tha

n

et a

l (20

10)

10

year

s wer

e in

clud

ed.

com

pare

d w

ith c

hron

ic

hab

its, f

ood

inta

ke

HBV

pat

ient

s.

3

1.8%

wer

e di

agno

sed

v

iral h

epat

itis p

atie

nts

N

AFL

D a

nd H

CV

pat

ient

s con

sum

ed m

ore

low

-nut

rient

food

,

w

ith N

AFL

D, 4

8.1%

wer

e

in re

gard

to fo

od in

take

.

and

mor

e hi

gh-s

odiu

m fo

od th

an H

BV p

atie

nts.

dia

gnos

ed w

ith h

epat

itis C

M

ultiv

aria

te a

naly

sis

A

lso,

NA

FLD

pat

ient

s con

sum

ed le

ss c

alor

ies f

rom

frui

ts th

an

v

irus

(HC

V),

and

20.2

%

and

uni

varia

te a

naly

sis

c

hron

ic v

iral h

epat

itis p

atie

nts.

had

hep

atiti

s B v

irus (

HBV

). w

ere

perf

orm

ed.

S27.

M

usso

G,

64 n

on-o

bese

non

-dia

betic

N

AFL

D a

nd c

ontro

l B

ehav

iora

l: al

imen

tary

Per

sons

with

NA

FLD

had

low

er v

itam

ins A

and

E in

take

s tha

n

et a

l (20

08)

pat

ient

s with

NA

FLD

s

ubje

cts w

ere

com

pare

d

hab

its, v

itam

in in

take

c

ontro

l sub

ject

s.

a

nd 7

4 co

ntro

l sub

ject

s i

n re

gard

s to

food

inta

ke.

N

itrot

yros

ine

and

adip

onec

tin c

once

ntra

tions

and

vita

min

w

ithou

t liv

er d

isea

se.

A in

take

inde

pend

ently

pre

dict

ed a

lani

ne a

min

otra

nsfe

rase

con

cent

ratio

ns in

NA

FLD

pat

ient

s and

live

r his

tolo

gy in

a

s

ubgr

oup

of 2

9 su

bjec

ts w

ith b

iops

y-pr

oven

non

alco

holic

ste

atoh

epat

itis.

S26.

Ze

lber

-Sag

i S,

349

Isra

eli p

artic

ipan

ts,

Surv

ey, c

ross

-sec

tiona

l B

ehav

iora

l: al

imen

tary

Int

ake

of so

ft dr

inks

and

mea

t was

sign

ifica

ntly

ass

ocia

ted

with

e

t al (

2007

) 5

2.7%

mal

e, m

ean

age 5

0.7

stu

dy. A

ssoc

iatio

ns

hab

its, f

ood

inta

ke

an

incr

ease

d ris

k fo

r NA

FLD

.

±

10.

4, 3

0.9%

dia

gnos

ed

bet

wee

n di

etar

y ha

bits

Als

o, th

e N

AFL

D p

atie

nts h

ave

a te

nden

cy to

war

d lo

wer

inta

ke

with

pri

mar

y N

AFL

D.

and

pri

mar

y N

AFL

D

o

f fish

rich

in o

meg

a-3.

wer

e ex

plor

ed.

S29.

K

ang

H,

91 p

atie

nts w

ith N

AFL

D,

Patie

nts w

ith m

etab

olic

B

ehav

iora

l: al

imen

tary

Pat

ient

s with

met

abol

ic sy

ndro

me

cons

umed

mor

e ca

rboh

ydra

tes

e

t al (

2006

) 3

1 pa

tient

s (34

%) h

ad

syn

drom

e w

ere

com

pare

d h

abits

, foo

d in

take

a

nd le

ss fa

t com

pare

d w

ith th

ose

with

out m

etab

olic

synd

rom

e.

m

etab

olic

synd

rom

e.

with

thos

e w

ithou

t B

ehav

iora

l: ph

ysic

al

Tota

l dai

ly c

alor

ies,

prot

ein

cons

umpt

ion,

and

phy

sica

l act

ivity

m

etab

olic

synd

rom

e.

act

ivity

w

ere

sim

ilar f

or th

e tw

o gr

oups

.

The

con

trib

utio

n of

Met

abol

ic sy

ndro

me

in p

atie

nts w

ith N

AFL

D is

ass

ocia

ted

with

d

iffer

ent f

acto

rs (e

.g.,

mor

e ca

rboh

ydra

te a

nd le

ss fa

t int

ake

and

grea

ter h

isto

logi

c

die

tary

com

posi

tion,

sev

erity

.

phy

sica

l act

ivity

) to

N

AFL

D se

verit

y w

as

a

lso

estim

ated

.

Table

I (

Con

t.).

Stu

dies

sele

cted

to b

e re

view

ed.

Con

tinue

d


5094

Stu

dy

Au

thors

, Sa

mple

char

acte

rist

ics

Met

hod

Psy

cholo

gic

al

Res

ult

s

ye

ar

(N

o, ag

e, g

end

er,

fa

ctors

d

iag

nosi

s)

id

enti

fied

Beh

avio

ral f

acto

rs –

Sub

stan

ce c

onsu

mpt

ion:

cof

fee,

alc

ohol

, sm

okin

g

S4.

K

won

HK

, 77

pat

ient

s with

NA

FLD

M

ultiv

aria

ble

anal

ysis

B

ehav

iora

l: lif

etim

e M

oder

ate

lifet

ime

alco

hol c

onsu

mpt

ion

seem

s to

have

a

e

t al (

2014

) d

iagn

osed

by

biop

sy.

sho

wed

an

asso

ciat

ion

alc

ohol

con

sum

ptio

n p

rote

ctiv

e ef

fect

on

the

hist

olog

ical

seve

rity

of li

ver d

isea

se

F

ifty-

two

patie

nts h

ad a

b

etw

een

alco

hol

a

mon

g N

AFL

D p

atie

nts.

his

tory

of r

egul

ar a

lcoh

ol

con

sum

ptio

n, a

ge a

nd

con

sum

ptio

n.

dis

ease

seve

rity.

S

8.

Wal

ton

HB

, 28

6 pa

tient

s atte

ndin

g th

e N

orm

al c

ontro

ls w

ere

Beh

avio

ral:

alim

enta

ry P

atie

nts w

ith c

irrh

osis

dra

nk si

gnifi

cant

ly le

ss c

offe

e th

an th

ose

et a

l (20

13)

liv

er o

utpa

tient

dep

artm

ent

com

pare

d w

ith c

hron

ic

hab

its, c

offe

e in

take

w

ithou

t cir

rhos

is.

at t

he R

oyal

Infir

mar

y

liv

er d

isea

se p

atie

nts

Th

ere

wer

en’t

signi

fican

t diff

eren

ces i

n th

e am

ount

of c

offe

e

o

f Edi

nbur

gh p

artic

ipat

ed

(non

-alc

ohol

ic fa

tty li

ver

d

runk

by

liver

pat

ient

s and

the

cont

rol g

roup

s.

i

n th

e st

udy.

The

con

trol

dis

ease

and

alc

ohol

Cof

fee

drin

king

is a

ssoc

iate

d w

ith a

redu

ced

prev

alen

ce o

f

g

roup

was

form

ed o

f 100

r

elat

ed li

ver d

isea

se)

c

irrh

osis

in p

atie

nts w

ith c

hron

ic li

ver d

isea

se.

ort

hope

dic

outp

atie

nts

and

120

med

ical

stud

ents

.

95 p

atie

nts w

ere

diag

nose

d

w

ith c

irrh

osis

.

S

11.

Liu

Y,

8580

subj

ects

, 269

1 m

en,

Com

mun

ity b

ased

surv

ey

Beh

avio

ral:

smok

ing

The

com

bina

tion

of a

ctiv

e sm

okin

g an

d bo

dy m

ass i

ndex

(BM

I)

et a

l (20

13)

age

40

and

olde

r. N

AFL

D

in C

hina

. h

abits

(act

ive

and

w

as a

ssoc

iate

d w

ith th

e hi

ghes

t obs

erve

d od

d ra

tio fo

r NA

FLD

.

p

reva

lenc

e w

as 2

9.4%

pas

sive

smok

ing)

In

nev

er sm

okin

g w

omen

, pas

sive

smok

ing

duri

ng c

hild

hood

and

in

neve

r sm

oker

s, 34

.2%

a

dulth

ood

was

ass

ocia

ted

with

a 2

5% in

crea

se in

the

risk

for

in

form

er sm

oker

s, 27

.8%

N

AFL

D.

in

light

smok

ers,

30.8

%

in

mod

erat

e sm

oker

s,

4

3.5%

in h

eavy

smok

ers.

S16

. D

unn

W,

251

lifet

ime

non-

drin

kers

M

ultip

le o

rdin

al lo

gist

ic

Beh

avio

ral:

alco

hol

Whe

n co

mpa

red

to n

on-d

rink

ers,

mod

est d

rink

ers h

ad lo

wer

e

t al (

2012

) w

ere

com

pare

d to

331

r

egre

ssio

n w

as u

sed

to

con

sum

ptio

n o

dds o

f hav

ing

a di

agno

sis o

f NA

SH, l

ower

odd

s for

fibr

osis

m

odes

t dri

nker

s with

d

eter

min

e as

soci

atio

ns

a

nd b

allo

onin

g he

pato

cellu

lar i

njur

y.

bio

psy-

prov

en N

AFL

D

bet

wee

n al

coho

l

con

sum

ptio

n an

d se

verit

y

o

f NA

FLD

/NA

SH

S17

. K

oehl

er E

M,

2,81

1 pa

rtic

ipan

ts, m

ean

Logi

stic r

egre

ssio

n an

alysis

B

ehav

iora

l: sm

okin

g To

tal p

hysi

cal a

ctiv

ity, p

ack

year

s of s

mok

ing,

age

, as w

ell a

s

et a

l (20

12)

age

76.

4 ±

6.0

year

s. w

as u

sed

to a

sses

s h

abits

, phy

sica

l o

ther

var

iabl

es w

ere

asso

ciat

ed w

ith N

AFL

D.

Pre

vale

nce

of N

AFL

D

ass

ocia

tions

bet

wee

n co

- a

ctiv

ity

The

prev

alen

ce o

f NA

FLD

dec

reas

es w

ith a

dvan

cing

age

in th

e

w

as 3

5.1%

. v

aria

bles

and

seve

rity

eld

erly

.

of N

AFL

D.

Table

I (

Con

t.).

Stu

dies

sele

cted

to b

e re

view

ed.

Con

tinue

d


5095

Conclusions

Primarily associated with insulin resistance, NAFLD is actually considered the hepatic manifesta-tion of the metabolic syndrome58,59. The pathogenesis of NAFLD and the more severe NASH is yet unclear. So far, it appears multifactorial, with many mechani-sms being proposed as possible causes.

Our study attempted to identify some of the emo-tional, cognitive and behavioral factors associated with the evolution of NAFLD/NASH. The results of our analysis are limited, in part due to the lack of con-ceptual clarity in some of the studies reviewed, the very diverse samples used and the various methods of collecting and analyzing the resulting data.

Some investigations suggest that emotional factors like anxiety and depression could influen-ce the progression of chronic liver diseases, but further research is needed to establish the type and the causes of such a relationship.

For NAFLD patients, the most relevant areas of investigation for cognitive functioning concern those contents and processes related to the ability to initiate and maintain lifestyle changes. The co-gnitive mechanisms underlying dietary behaviors and engagement in physical activity are some of the most important targets for further investigation.

Intense physical exercise may act as a protective factor against the debut and aggravation of NAFLD symptoms. In the evolution of NAFLD, poor nutri-tion seems to play a central role and needs further in-vestigation. Some studies show there is an improve-ment in insulin resistance and hypertransaminasemia following hypocaloric diets in NAFLD patients60.

Contrary to the effect of coffee consumption and moderate alcohol drinking, smoking may have a detrimental effect on NAFLD evolution.

In conclusion, some of the factors identified act as protective factors, other as vulnerability factors. NAFLD/NASH may be considered a cognitive-behavioral disease, the most effective management being lifestyle changes, with em-phasis on diet and exercise.

Conflict of interestThe Authors declare that they have no conflict of interests.

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ud

y A

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char

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cholo

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11)

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AFL

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Surv

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ehav

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e pr

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AFL

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er in

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ine

e

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45 m

odes

t win

e dr

inke

rs

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ssoc

iatio

ns

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ptio

n d

rink

ers w

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pare

d to

non

drin

kers

.

w

ere

incl

uded

in th

e st

udy.

be

twee

n al

coho

l

con

sum

ptio

n an

d N

AFL

D

wer

e ex

plor

ed.

Table

I (

Con

t.).

Stu

dies

sele

cted

to b

e re

view

ed.


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Psychological factors associated with NAFLD/NASH- a ......Psychological factors associated with NAFLD/NASH: a systematic review 5083 Inclusion Criteria At least one psychological factor