Possible association between non-alcoholic fatty liver disease and metabolic syndrome

102 Pages·2016·1.6 MB·English

Al-Azhar University - Gaza
Deanship of Postgraduate Studies
Faculty of Science
Biology Department
Biological Sciences Master Program

Possible association between non-alcoholic fatty liver
disease and metabolic syndrome (case-control study)

By:
Suliman Khalil Abu Hasanien
B.Sc. Laboratory Medicine

Supervisors:
Prof. Dr. Abdelnasser K. AbuShahla Dr. Nahed Al Laham
Prof. of Biochemistry Assoc. Prof. of Medical and Molecular
Microbiology

Thesis Submitted in Partial Fulfillment of the Requirements for the
Master Degree of Science in Biological Sciences.
2016
Declaration

I hereby declare that this submission is my own work and that, to the best of my
knowledge and belief, it contains no material previously published or written by
another person nor material which to a substantial extent has been accepted for
the award of any other degree of the university or other institute, except where
due acknowledgment has been made in the text.

Signature Date
Suliman Khalil Abu Hasanien 2016

All rights reserved: No part of this work can be copied, translated or stored in
any kind of a retrieval system, without prior permission of the author and the
supervisor.

II
Dedication
To
my great parents

To
my brothers and sisters

To
martyrs and prisoners of Palestine

To
colleagues in the Red Crescent Society for Gaza Strip

To all of them I dedicate this work.

III
Acknowledgment
All praise to ALLAH (Almighty), the Beneficent, the Merciful, without his
mercy and guidance this work and the other works never has been started nor
completed. I praise to ALLAH (Almighty) as much as the heavens and earth and
what is between or behind.
I express my sincere thanks to my supervisors:
Dr. Abdelnasser K. AbuShahla (Professor of Biochemistry), Biology
Department, Faculty of science, Al-Azhar university – Gaza.
Dr. Nahed Al Laham, (associate professor of medical and molecular
microbiology), department of medical laboratory sciences, faculty of applied
medical sciences, Al-Azhar university – Gaza.

IV
Possible association between non-alcoholic fatty liver disease and metabolic
syndrome (case-control study)
Suliman Khalil Abu Hasanien
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a pathological status, that is
defined as lipid accumulation in the cytoplasm of hepatocytes, where tri-
acylglycerol (TG) accumulation inside the hepatocytes is the etiological factor
for NAFLD. On the other hand, metabolic syndrome is defined as a collection
of abnormalities combined with risk factors, such as obesity, lipid and
carbohydrate metabolism disorders, and arterial hypertension.
The present study aimed to find out possible association between non-alcoholic
fatty liver disease and metabolic syndrome among adult males and females in
Gaza and also to determine the prevalence of non-alcoholic fatty liver disease in
Gaza.
This is a case-control prospective study, adults who were diagnosed by a
Radiologist with (NAFLD) in center of Gaza were included in this research. The
study sample included 300 individuals (150 case, 150 healthy control), aged 35-
65 years. Socio-demographic and clinical data were collected by questionnaire
interview and venous blood sample were collected for biochemical analysis.
For all study subjects, serum fast blood sugar (FBS), total cholesterol,
triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein
(LDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)
were determined for overnight fasting venous blood. Body mass index (BMI),
waist circumference (WC) and blood pressure (Bp) were measured.
About two third of cases in this study who suffered of NFALD have metabolic
syndrome (66%), while none of controls have the metabolic syndrome (0.0%).
There is a significant difference between cases and control groups (χ2=147.761,
V
P< 0.001). The overall prevalence of NAFLD was 7.14% of the study
population, and it was significantly higher in women than in men (54.66 % and
45.43%, respectively). The highest percent of NAFLD cases was found in the
age group 46-55 years (41.34%), followed by 35-45 years (30%) and 56-65
years (28.7%). There was a significant difference between the monthly income,
smoking habit and food type of the cases and the controls (P=0.015, P< 0.001,
P=0.004 respectively). More than half of NAFLD cases have significantly
increased glucose level (54.66%) and inherited Diabetes Mellitus (52.66%)
compared to controls (P < 0.001). Also, heart disease, (P< 0.001), inherited
heart disease (P=0.001), cholesterol elevation (P< 0.001), triglyceride elevation
(P<0.001), blood pressure elevation (P<0.001), inherited blood pressure
elevation (P<0.001), increased ALT (P<0.001) and AST levels (P<0.001).
About two-third of cases were not playing sport (66%) (P=0.001), and 76.7%
were using drugs for treatment (P<0.001). The mean value of fasting blood
glucose, cholesterol, triglyceride and low density lipoprotein in NAFLD cases
was higher than in the controls, while the mean value of High Density
Lipoprotein (HDL)in controls (52.02 mg/dl) was higher than in cases (37.70
mg/dl).
NFALD disease was found to be significantly associated with metabolic
syndrome. There was significant high number of NAFLD cases who smoke,
having high blood glucose level, inherited Diabetes Mellitus, heart disease,
inherited heart disease, high cholesterol level, high triglyceride level, blood
pressure elevation, inherited blood pressure elevation and abnormal levels of
liver enzymes AST and ALT.

Keywords: Non-alcoholic fatty liver disease; Metabolic syndrome; Prevalence;
Gaza.

VI
)هلاح ةسارد( ضيلأا ةمزلاتمو ىلوحكلالا ينهدلا دبكلا نيب تاقلاع دوجو ةيلامتحا
نينسح وبا ليلخ ناميلس
:ثحبلا صخلم
150 300
65 35 150
66

.(χ2=147.761, P< 0.001)
7.14
45.43 54.66
41.34 55 46
28.7 65 56 30 45 35
VII
(P=0.015, P< 0.001, P=0.004 )
(P < 0.001) 52.66 54.66
(P (P =0.001) (P < 0.001).
(P < 0.001) (P < 0.001) < 0.001)
.(P < 0.001)
(P < 76.7 (P =0.001) 66
0.001)
(52.02 mg/dl)
(37.70 mg/dl)

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List of Contents Page
Declaration ɪɪ
Copyright ɪɪ
Dedication ɪɪɪ
Acknowledgment ɪv
Abstract (English) v
Abstract (Arabic) vɪɪ
Table of contents ɪx
List of Tables xɪɪ
List of Figures xɪv
List of abbreviations xvɪ

1: Introduction and aims of the work
1.1Overview 1
1.2 Problem of statement 4
1.3 General objectives 5
1.4 Specific objectives 5

2: Literature review
2.1 Non-alcoholic fatty liver disease 6
2.2 Metabolic syndrome 8
2.3 Pathogenesis 10
2.3.1 Insulin resistance-free fatty acid flux and hyperinsulinemia 11
2.3.2 Endoplasmic reticulum stress 11
2.3.3 Role of oxidative stress - mitochondrial dysfunction 11
2.3.4 Inflammation and adipokines 12
2.3.5 Gut-microbial alteration and TRLs stimulation 12
2.4 Prognosis 13
2.5 Clinical finding 14
2.6 Imaging studies 14
2.7 Diagnosis of metabolic syndrome 15
2.8 Staging and grading of NAFLD 15
2.8.1 Mild (grade 1) 15
2.8.2 Moderate (grade 2) 15
2.8.3 Severe (grade 3) 16
2.9 Epidemiology of NAFLD 16
2.10 Hypolipidemic agents and NAFLD 17
2.10.1 Statins 17
IX
2.10.1.1 Atrovastatin 18
2.10.1.2 Simvastatin 18
2.10.1.3 Rosuvastatin 18
2.10.1.4 Parvastatin 18
2.10.2 Fibrates 19
2.10.3 Ezetimibe 19
2.10.4 Omega 3-fatty acids 19
2.11 Lifestyle intervention 20

3 :Materials and Method
3.1 Study design and target population 21
3.2 Setting of the study 21
3.3 Period of study 21
3.4 Study population and sample size 21
3.5 Inclusion criteria 22
3.6 Ethical consideration 22
3.7 Samples collection 22
3.8 Chemical and reagent 23
3.9 Data collection 24
3.9.1 Body mass index measurement 24
3.9.2 Waist circumference measurement 24
3.9.3 Blood pressure measurement 25
3.10 Testing of samples 25
3.10.1 Fast blood glucose 25
3.10.2 Aspartate aminotransferase (AST) 26
3.10.3 Alanine aminotransferase (ALT) 28
3.10.4 Triglycerides 29
3.10.5 Cholesterol total 30
3.10.6 HDL precipitant 31
3.11 Questionnaire 32
3.11.1 Demographic data 32
3.12 Data analysis 32

4: Results
4.1 General characteristic of study population 33
4.1.1 Distribution of study population according to age 34
4.1.2 Distribution of study population according to monthly income 35
4.2 Questionnaire Analysis: 36
4.2.1 Smoking 36
4.2.2 Food type 37
4.2.3 Glucose elevation 39
4.2.4 Inherited diabetes mellitus 40
4.2.5 Heart disease 41
4.2.6 Inherited heart disease 42
X