Evaluation of serum connective tissue growth factor [CTGF] as a new noninvasive marker for assessment of hepatic fibrogenesis in children with chronic liver diseases

On the basis of the molecular pathogenesis of fibrosis, several studies have initiated evaluation of the diagnostic value of serum connective tissue growth factor [CTGF] as a potential fibrogenic marker. Clinical and experimental studies have demonstrated that connective-tissue growth factor [CTGF] expression is increased in fibrotic human liver and experimental animal models of liver fibrogenesis. CTGF has been linked to transforming growth factor-beta [TGF-fi] pathways in fibroproliferative diseases. As CTGF is detectable in various human fluids [serum, plasma and urine], it may provide information about fibrotic, remodelling processes and reflect hepatic TGF-/3 bioactivity. Recently, assessment of serum CTGF concentrations was investigated as a possible non-invasive indicator of liver fibrosis in patients with hepatic fibrosis. The aim of this work was to investigate the serum level of CTGF in children with chronic viral hepatitis and those with liver cirrhosis and to assess the correlation between serum concentration of CTGF and stage of hepatic fibrosis to determine the clinical value of serum CTGF as a noninvasive biomarker for hepatic fibrogenesis. This study was conducted on 30 patients with chronic hepatitis and 20 patients with liver cirrhosis. Their ages ranged from 2 to 16 years. Twenty healthy children with matched age and sex were chosen as a control group. The patients were selected from those admitted to the Hepatology Unit of Pediatric Department, Tanta University Hospitals. In this study all patients were subjected to the following: full clinical history, thorough physical examination, abdominal ultrasonography, and laboratory investigations. The latter included complete blood count, liver function tests, blood urea, serum creatinine, hepatitis markers as well as measurement of serum CTGF concentration utilizing enzyme-linked immunosorbent assay [ELISA]. Histopathological assessment of liver biopsy with special emphasis on staging of liver fibrosis and grading of necroinflammation in patients with chronic hepatitis. Severity of liver dysfunction in cirrhotic patients was classified into stages A, B and C according to modified Child-Pugh's classification. Control children were subjected to the whole previous investigations except liver biopsy. This study showed that CTGF serum levels were significantly higher in patients with chronic hepatitis compared with healthy controls. Furthermore, progression of liver fibrosis to stage F4 in patients with chronic hepatitis was accompanied by a considerable increase of the CTGF serum concentration. Serum CTGF levels correlated with the stage of liver fibrosis in chronic hepatitis patients. In the present study, cirrhotic patients displayed higher serum CTGFconcentrations than healthy controls. Conversely, cirrhotic patients displayed lower serum CTGF concentrations than patients with chronic hepatitis. From this study, we can conclude that serum CTGF could become a valuable non-invasive diagnostic marker of liver fibrosis and could be considered as an indicator for the stage of liver fibrosis and may represent a potential novel noninvasive biomarker of ongoing liver fibrogenesisf especially in patients with chronic viral hepatitis. Further prospective comparative studies involving large numbers of patients with chronic viral hepatitis who have varying degrees [grades] of activity of disease but similar stages of fibrosis are warranted to investigate the prognostic value of serum CTGF to determine its usefulness for clinical practice in the setting of chronic liver diseases and liver fibrosis

Non-invasive evaluation of liver fibrosis using transient elastography in children with nonalcoholic steatohepatitis

Over the last decades, the prevalence of overweight and obesity among children has increased dramatically worldwide with subsequent increase of the nonalcoholic fatty liver disease [NAFLD] and its progressive entity called nonalcoholic Steatohepatitis [NASH]. Liver fibrosis is the main predictor of the progression of NAFLD. Liver biopsy is recommended as the gold standard method for the diagnosis as well as staging of fibrosis in NASH patients. However, it is an invasive procedure and is associated with a relatively high risk of complications. Transient elastography [FibroScan] which measures liver stiffness, is a novel, noninvasive method to assess liver fibrosis. But still it need to be searched and validated in pedriatic population especially those affected by NASH-related liver fibrosis. The aim of this work was to evaluate liver stiffness measurement [LSM] using non-invasive transient elastography [Fibroscan] in comparison with liver biopsy for the assessment of hepatic fibrosis in children with nonalcoholic Steatohepatitis [NASH]. This study was conducted upon 50 children [29 males and 21 females] with biopsy-confirmed NASH. Their ages ranged from 6 to 18 years with a mean age of 12.7 +/- 2.44 years. In this study all patients were subjected to the following: full clinical history, thorough physical examination, abdominal ultrasonographyt laboratory investigations, histopathological assessment of liver biopsy and liver stiffness measurement [LSM] using FibroScan. The laboratory investigations included complete blood count, liver junction tests, hepatitis markers, fasting blood glucose and lipid profile. We found that the mean values of liver stiffness in patients with different stages of liver fibrosis were as follow: 5.93 +/- 2.68 kPa for FO, 7.92 +/- 2.82 kPa for F1, 9.11 +/- 3.6 kPa for F2, 15.14 +/- 4.03 kPa for F3 and 25.76 +/- 8.31 kPa for F4. There was a highly significant stepwise increase of LSMs [p<0.001] with increasing histological severity of hepatic fibrosis with the highest value detected in stage F4 [cirrhosis]. We found significant correlations between LSM and Brunt fibrosis stages [r=0.777, p<0.001]. In contrast, there was no correlation between LSM and both of necroinflammatory activity grades [r=0.247, p=0.087] as well as steatosis grades [r=0.008f p=0.959] in children with NASH. As regard the diagnostic accuracy of LSM for the prediction of liver fibrosis stages in this study, there was progressive elevation of accuracy with increasing stage of liver fibrosis as follow: for F >/= sensitivity of 85.2%, specificity of 87.3% and accuracy of 80% were detected at cutoff value of 5.6 kPa; for F >/= sensitivity of 87.3%% specificity of 72.8% and accuracy of 90% were detected at cutoff value of 6.7 kPa; for F >/= 3 sensitivity of 88.6%, specificity of 82.5%, and accuracy of 96% were detected at cutoff value of 9.7 kPa; for F =4 sensitivity of 100%, specificity of 95.5%, and accuracy of 100% were detected at cutoff value of 17.5 kPa. At the different cutoff values [5.6, 6.7, 9.7, 17.5 kPa], we found high negative predictive values [60.3%, 84.4%, 95.2%, 100%] and modest positive predictive values [95.2%, 73.5%, 62.7%, 74.3%], respectively. Measurement of the liver stiffness using [FibroScan] is a rapid, accurate, noninvasive, clinically useful technique for predicting the severity of liver fibrosis especially in advanced stages among children with NASH. As transient elastography is painless, rapid, and easy to perform at the bedside or in the outpatient clinic; it could be performed and repeated as necessary to monitor progression of liver fibrosis and to evaluate the effect of diet or medication on NASH-related liver fibrosis. However, additional large-scale multicentre controlled studies arenecessary to define the optimal thresholds of liver stiffness and to investigate the value of TE for monitoring therapeutical approaches in larger cohorts of NASH patients