الفهرس 
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Abstract
Summary
C
hronic liver diseases (CLD) and its end-stages, cirrhosis and hepatocelluler carcinoma, are leading causes of morbidity and mortality worldwide with enormous socioeconomic costs.
Hepatitis C virus (HCV) infection, the most common cause of CLD, is estimated to affect 170 million individuals worldwide (2% of the world’s population). The recently published Egyptian Demographic Health Survey (EDHS) in 2009 estimated an overall anti-HCV antibody prevalence of 14.7%. The number of Egyptians estimated to be chronically infected was 9.8% whereas, more than 500,000 new HCV infections occur every year.
For almost all causes of chronic liver disease, assessment of fibrosis is important in estimating the progression of liver damage. Liver biopsy is still the standard and most commonly used procedure in the assessment of liver fibrosis. However, it is an invasive method associated with patient discomfort and, in rare cases, with serious complications.
The limitations of the procedure have prompted the search for non-invasive markers of hepatic fibrosis. Non-invasive procedures such FibroScan and serum biomarker panels (particularly Fibrotest and Hepascore) have been developed in order to avoid biopsy, however, although significant advances have been achieved in this field, none of the currently available indices has sufficient accuracy to replace liver biopsy in the assessment of hepatic histology in patients with chronic HCV infection. The primary limitation of these indices is their inability to identify patients with intermediate stages of fibrosis.
It has been previously reported that OPN is expressed in activated Kupffer cells and stellate cells in experimentally liver necrosis (OPN) was also shown to play an important role in the pathogenesis of various inflammatory and fibrotic processes and elevated in fibrotic liver of mouse model. Moreover, elevated OPN levels were found in patients with early stages of HCC and were associated with poorer prognosis.
These data suggest that OPN is correlated with the progression of liver disease, In this regard, our study aimed at the evaluation of the clinical utility of OPN serum level as a marker for prediction of degree of fibrosis in HCV-related chronic liver diseases, and to correlate its levels with the results of liver biopsy in patients with no evidence of hepatic cirrhosis by ultrasonography or with the Child-Pugh Classification in cirrhotic patients.
This study was conducted on 60 patients with positive HCV RNA by quantitative RT-PCR for more than 6 months, attending at the Gastroenterology and Hepatology department at Ain Shams University Hospitals, who were further classified according to the stage of liver disease into: 20 HCV positive patients with no evidence of liver cirrhosis by ultrasonography and who were subjected to a liver biopsy for assessment of degree of fibrosis (non-cirrhotic group), 40 patients with cirrhosis, who were further classified according to Child-Pugh Classification into A, B and C subgroups (cirrhotic group), in addition to 20 apparently healthy, HCV-seronegative and HBV-seronegative subjects as healthy controls. All participants in the study were subjected to abdominal ultrasound to detect patients with established cirrhosis, liver biopsy for patients with no evidence of cirrhosis, measurements of: HCV RNA by RT- PCR, HBS Ag, 2 hour postprandial blood sugar to exclude diabetes, liver profile (AST, ALT, serum bilirubin, total protein, serum albumin, prothrombin time), serum concentration of OPN using enzyme linked immunosorbent assay (ELISA).
Results of the present study showed that the measured OPN levels were significantly higher among CLD patients when compared to control subjects (P< 0.001). Moreover, there was a statistically highly significant increase of OPN among cirrhotic group when compared to non-cirrhotic and control groups (P< 0.001). As regards its role in assessment of fibrosis.A statistically high significant increase was recorded in patients with mild fibrosis when compared to severe (P<0.01). Moreover, there was a highly significant difference in OPN level on comparing the subgroup of mild fibrosis against both the moderate to severe fibrosis. Finally, in the cirrhotic group, significantly higher levels of OPN among patients of subgroup B and C was noted when compared to those of subgroup A with inverse correlation between OPN levels and serum albumin was found (P<0.05).
Receiver Operating characteristic (ROC) curve analysis of the diagnostic performance of the studied marker, OPN, to assess its ability to predict cirrhosis. The test was able to discriminate non-cirrhotic group from healthy group with the diagnostic cutoff of 550 pg/mL. This had a diagnostic specificity of 80%, sensitivity70%, negative predictive value72.7 %, positive predictive value77.8 % and accuracy 75%. The area under curve (AUC) was 0.791.
The favorable cutoff level of the OPN to discriminate the severity of liver disease was assessed by ROC curve where the best ROC cutoff level of the OPN to predicte fibrosis in mild fibrosis versus moderate or severe fibrosis was 750 pg/mL. This had a diagnostic specificity of 66.7%, sensitivity 100%, negative predictive value 100%, positive predictive value 78.7% and accuracy 85%. The area under curve (AUC) was 0.826.
In conclusion; OPN at a concentration of <750 pg/mL may exclude the occurance of significant fibrosis with a negative predictive value 100%. Also, OPN shows significant elevation with progression in fibrosis in chronic HCV infected subjects. However, no consensus on a cutoff value has been reached to differentiate the stage of fibrosis