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

Cyclosporin A-induced gingival overgrowth is not associated with myofibroblast transdifferentiation

Cyclosporin A (CyA) induces gingival overgrowth via its stimulatory effects on expression of transforming growth factor-beta1 (TGF-â1) and collagen. It is not known whether CyA has a direct effect on gingival fibroblasts or induces its effect indirectly via stimulation of myofibroblast transdifferentiation. The present study was undertaken to examine the in vivo and in vitro effect of CyA on myofibroblast transdifferentiation. Rats were treated for 60 days with a daily subcutaneous injection of CyA, and the gingival overgrowth tissue was analyzed by immunohistochemistry. In vitro, fibroblasts from normal gingiva (NG) were cultured in the presence of different concentrations of CyA, and subjected to semi-quantitative reverse transcriptase-polymerase chain reaction and western blot. Although CyA treatment stimulated TGF-â1 expression by NG fibroblasts, it lacked to induce expression and production of isoform á of smooth muscle actin (á-SMA), the specific myofibroblast marker. The expression levels of connective tissue growth factor (CTGF), which has been considered a key molecule to promote the transdifferentiation of myofibroblasts via TGF-â1 activation, were unaffected by CyA. Our results demonstrate that CyA-induced gingival overgrowth is not associated with activation of myofibroblast transdifferentiation, since CyA is not capable to increase CTGF expression.