الفهرس 
Chronic Liver DiseaseOnly 14 pages are availabe for public view
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Abstract
Chronic 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 number of Egyptians estimated to be chronically infected is 9.8% (more than 500,000 new HCV infections occur every year).
In nearly all liver diseases, progression from healthy tissue to cirrhosis is mediated by a chronic inflammatory reaction within the liver parenchyma that activates stellate cells and leads to the excess deposition of extracellular matrix proteins. The recruitment of immune cells into the damaged liver is orchestrated by chemokines, a class of soluble immune mediators with variable chemotactic and cytokine-like functions that alter the architecture of the liver as a result of excessive scarring, development of small nodules, and changes in liver tissue.
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 Fibrometre, 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 IP-10 is expressed in hepatocytes and its serum levels are increased in patients with chronic hepatitis especially HCV infection. IP-10 is specifically produced by hepatocytes in inflammatory areas, and may help to recruit T cells to the hepatic lesions in chronic viral hepatitis. These data have tempted researchers to study IP-10 as a potential marker for degree of liver fibrosis.
In this regard, our study aimed at the evaluation of the clinical utility of IP-10 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 55 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: Twenty five 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), thirty patients with cirrhosis, who were further classified according to Child-Pugh Classification into A, B and C subgroups (cirrhotic group), in addition to 25 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, HBSAg, 2 hour postprandial blood sugar to exclude diabetes, liver profile (AST, ALT, serum bilirubin, total protein, serum albumin, prothrombin time), serum concentration of IP-10 using enzyme linked immunosorbent assay (ELISA).
Results of the present study showed that the measured IP-10 levels were significantly higher among CLD patients when compared to control subjects (P< 0.001). Moreover, there was a statistically highly significant increase of IP-10 among cirrhotic group when compared to non-cirrhotic and control groups (P< 0.001). As regards its role in assessment of fibrosis, a statistically highly significant increase in IP-10 was noticed among patients with severe fibrosis, compared to those with moderate or mild degree (P<0.001). Moreover, a statistically highly significant increase was recorded in patients with mild fibrosis when compared to severe (P<0.001). Finally, a significant increase was found in moderate degrees when compared to severe (P<0.05).
Receiver Operating Characteristic (ROC) curve analysis of the diagnostic performance of the studied marker, IP-10, in CLD patients versus the control group revealed a high discriminatory power of the test as evidenced by an area under curve (AUC) of 0.965 at a cutoff value of 420 pg/mL. The test was also able to discriminate non-cirrhotic group from healthy group with an AUC of 0.995 at the same cutoff level (420 pg/mL).
The favorable cutoff level of the IP-10 in patients with mild or moderate degree of fibrosis versus severe was 850 pg/mL, This had a diagnostic specificity of 85.7%, sensitivity 90.9%, negative predictive value 92.3%, positive predictive value 83.3% and accuracy 88.3% with an AUC of 0.955. Moreover, the same cutoff (850pg/mL) had a diagnostic specificity of 100%, sensitivity 85.7%, negative predictive value 84.6%, positive predictive value 100% and accuracy 93% with an AUC of 0.955, for discriminating patients with mild from those with moderate or severe fibrosis.