الفهرس | Only 14 pages are availabe for public view |
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 188 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 Summary 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%. |