Hyaluronic Acid & Carnitine Profile In Children with Chronic Liver Diseases

number: 
2995
إنجليزية
Degree: 
Imprint: 
Medicine
Author: 
Nadia Noori Hassan
Supervisor: 
Dr.Firyal Hassan AL- Obaidi
Dr.Hala Sameh Arif
year: 
2012
Abstract:

Successful individualized management of chronic liver disease depends on the correct staging of liver fibrosis. In order to provide the means of monitoring the course of liver disease and its response to therapy, staging it is better to be performed in a non-invasive and reproducible manner. The fact that the process of fibrogenesis is a component of the normal healing response hampers the development of disease-specific biomarkers; this is why the quest for suitable non-invasive biomarker of liver fibrosis has become one of the biggest challenges in translational hepatology. A number of non-invasive techniques ranging from serum biomarker assays to advanced imaging techniques are being developed. This review discusses the role of some noninvasive tests to diagnose liver disease and to assess hepatic fibrosis and cirrhosis. Objective: To assess the clinical value of serum hyaluronic acid (HA), aspartate aminotransferase(AST), alanine aminotransferase (ALT), total serum bilirubin (TSB) and carnitine profile as a functional and fibrogenesis markers in children with chronic liver disease. Subject and methods: The study was conducted during the period from September 2011 till August 2012 in the Department of Chemistry and Biochemistry/College of Medicine/Al-Nahrain University. It includes fifty children with different type of chronic liver diseases (CLDs) who were attended to: 1- Al-Kadhimiya Teaching Hospital (Pediatric Department) 2-Children Welsar Teaching Hospital 3-Gastroenterology and Hepatology center (medical city). These (50) patients were divided into (31) children with significant fibrosis and (19) without significant fibrosis, (18) of these cases were assessed by undergoing to liver biopsy at Gastroenterology and Hepatology center (medical city), and (32) were subjected to U/S evaluation at the same hospital. Thirty (30) healthy children were taken as controls (control І). Hyaluronic acid (HA), AST, ALT, TSB and AST/ALT ratio were measured for both the fifty patients and the thirty healthy children (control І). Hyaluronic acid was measured by commercial Enzyme Linked Immuno Sorbent Assay (ELISA) kit, AST, ALT, TSB were determined by a spectrophotometric methods. Twenty four (24) from these (50) patients were taken to evaluate carnitine profile, (10) of them have cholestasis, (7) have cirrhotic liver and (7) of them have CLDs due to other causes than cholestasis with normal histological liver and considered as control (control ІI). Carnitine profile was measured by Tandem Mass Spectrometry. Results: The results of the study showed that the mean of hyaluronic acid levels were significantly higher in group of children CLDs with significant fibrosis compared to control (І) (p> 0.0001), the mean of hyaluronic acid levels were also significantly higher in group of children CLDs without significant fibrosis compared to control (І) (p= 0.0108) , the results also demonstrated there were high significant differences in the mean of hyaluronic acid levels between children with significant fibrosis and children without significant fibrosis (p> 0.0001). The cutoff value of hyaluronic acid was calculated using receiver operating characteristic (ROC) test and it was 1.66 ng/mL, the sensitivity and specificity of estimation of HA value in diagnosis of liver cirrhosis were 87.1% and 94.74% respectively, while the positive predictive value of HA in diagnosis of liver cirrhosis was 96.43% and the negative predictive value was 81.82%. The means of AST, ALT and TSB levels were significantly higher in children with CLDs with significant fibrosis compared to control (І) (p> 0.0001, p> 0.0001 and p=0.0001) respectively. Also the mean of those markers were significantly higher in children with CLDs even without significant fibrosis compared to control (І) (p= 0.0001, p= 0.0007 and 0.007) respectively. The mean of AST/ALT ratios were significantly higher in children with CLDs with significant fibrosis compared to control (І) (p= 0.0113), whereas there is no significant differences in the mean of AST/ALT ratio between the patients without significant fibrosis and control (І) (p= 0.0834). The means of carnitine profile of (24) children showed low levels in all the three groups (10 cirrhosis, 7 cholestasis, 7 children of CLDs with normal histological liver which used as control (ІІ) and no significant differences were found between them, But a statistically significant correlation was found only in the mean of level of long chain acylcarnitine/free carnitine ratio between the children of cholestasis and control (ІІ) (p= 0.039). Conclusion: From these findings it was concluded that serum HA level is a good marker in determining the severity of CLDS and the grade of liver fibrosis in children with chronic liver diseases.AST, ALT and TSB levels were be useful markers in diagnosis the CLDs but not in determining the grade of fibrosis, while the AST/ALT ratio was a good indicator for advanced stage of liver disease. Children with CLDs and cirrhosis have low plasma carnitine concentrations that reflect the low functional activity of the liver rather than the histological grade.