الفهرس 
Non Alcoholic Fatty Liver DiseaseOnly 14 pages are availabe for public view
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Abstract
Non alcoholic fatty liver disease (NAFLD) is
recognized as a clinical and pathological entity evolving
from simple steatosis towards steatohepatitis, advanced
fibrosis, liver failure and, in some cases, hepatocellular
carcinoma.
The prevalence of non-alcoholic fatty liver disease
(NAFLD) is increasing in the context of the general
epidemics of obesity and diabetes mellitus, which has
become a public health issue. The clinical importance of this
condition is not only due to its high prevalence in the general
population, but also to the wide spectrum of risk factors, the
indisputable link to the metabolic syndrome and the
potential evolution towards cirrhosis and hepatocellular
carcinoma.
The diagnosis of NAFLD was traditionally based on the
histopathological changes of the liver, evaluated by needle
liver biopsy (LB). Unfortunately, this is an invasive method,
with potential adverse effects. Therefore, rapid, noninvasive
assessment methods are being currently researched for non
alcoholic fatty liver (NAFLD) patients.
Many clinical variables have been proposed until now
as predictors of severity in patients with NAFLD, including
old age, underlying type 2 diabetes mellitus, obesity, serum
transaminase levels, platelet count, etc. Several clinical
studies have attempted to identify serum markers that might
be correlated with the severity of histopathological findings
in these patients.
The present study aimed to study the significance of
serum level of transforming growth factor β 1 (TGFβ1),
serum matrix metalloproteinase (MMP-1) level and insulin
resistance in comparison to liver biopsy in predicting the
Summary
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severity of non alcoholic fatty liver disease (NAFLD) in
egyptian patients.
This study was divided into three groups according to
Kleiner et al., (2005) classification of degree of steatosis.
Group I included 25 NAFLD patients, with 5 to 66%
steatosis of hepatocytes. Group II include 25 NAFLD
patients, showing steatosis affecting more than 66 % of
hepatocytes. Group III included 15 healthy individuals with
matched age and sex.
All patients were subjected to full history taking and
clinical examination, routine laboratory investigations, lipid
profile, fasting and two hours post prandial blood sugar,
serological markers to exclude other causes of chronic liver
diseases, abdominal ultrasonographic examination,
transcutaneous liver biopsy, histopathological examination of
the liver biopsies, serum level of transforming growth factor
β 1 (TGFβ1), serum matrix metalloproteinase (MMP-1) level
and insulin resistance by calculation of the HOMA-IR
(Homeostasis Model Assessment for Insulin Resistance).
This study revealed that there was a significant increase
in age, BMI, incidence rate of diabetes mellitus, obesity and
hyperlipidemia with higher grades of steatosis and also most of
patients had elevated liver enzymes and other liver profiles
were not affected.
Histopathological data of this study revealed that type of
steatosis in most of patients was macovesicular type and there
was a trend of increasing necro-inflammatory changes and
stages of fibrosis with higher percentage of steatosis.
In this study, significant difference of serum TGFB1
levels in all grades of steatohepatitis patients in contrast to
control group. Staging was the only factor affecting level of
TGFB1. It was found that TGFB1 showed excellent ability to
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189
predict different stages with optimum cut off values. For F1
the optimal cut-off value was 14.5ng/ml with a sensitivity of
100%, specificity 94.4%, for F2 the optimal cut-off value was
26ng/ml with a sensitivity of 100%, specificity 93.9% and for
F3 the optimal cut-off value was 36.6ng/ml with a sensitivity
of 97.7%, specificity 100%.
Regarding HOMA-IR there was significant difference
between the three categories of NAS score. Also, there was a
significant increase in mean of HOMA-IR with the increase in
the stage of fibrosis. We found that steatotosis grades and
staging were the factors affecting HOMA-IR. HOMA-IR
showed excellent ability to predict different stages with
optimum cut off values. For F1 the optimal cut-off value was
4.1 with a sensitivity of 100%, specificity 88.89%, for F2 the
optimal cut-off value was 5.8 with a sensitivity of 100%,
specificity 84.85% and for F3 the optimal cut-off value was
8.5 with a sensitivity of 100%, specificity 100%.
As for serum MMP-1, there was no difference in the
serum level of MMP-1 between patients and normal controls.
However, a declining tendency in the serum level of MMP-1
with the severity of liver fibrosis was observed. We found that
MMP1 could not differentiate F1. But for F2 the optimal cutoff
value was 2.7 with a sensitivity of 88.2%, specificity
81.82% and for F3 the optimal cut-off value was <2.1 with a
sensitivity of 83.3%, specificity 90.91%.