الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 213 |  |  |
| | | from | 213 | | |
Abstract
SUMMARY epatocellular carcinoma (HCC) is the 5th most common cancer Worldwide and the 3rd leading cause of cancer-related death; with about 600,000 patients dying from the disease annually. Among the main risk factors for HCC, chronic infections of hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most important in humans, accounting for more than 70% of HCC cases worldwide. Hepatitis C virus has a major impact on public health, infects around 170 million people in the World, with an estimated global incidence of three to four million new infections per year (Miller et al., 2010). In Egypt, HCV is the most leading cause of HCC and it is known for being the country in the World with the highest prevalence of HCV, where about 24% of the people are estimated to carry HCV (Anwar et al., 2008). The diagnosis of HCC is mainly based on measurement of serum alpha-fetoprotein (AFP), along with ultrasound every 6 to 12 months. However, The clinical use of AFP has been shown to present some important limitations in sensitivity and specificity, and hence, it is ineffective for diagnosis of early stages of the disease (Bertino et al., 2011). Also, Ultrasound surveillance cannot improve detection of small HCC because of limitations in the procedure (Radoslav et al., 2009). This H
Summary
141
makes early detection of HCC an active area of research, where several new candidate markers were reported within the last few years (Trinchet et al., 2011). Glutamine synthetase (GS), also called glutamine ammonia ligase, is a 373 amino acid, 42 KDa molecule coded by the GLUL gene on chromosome 1q31. GS is present in various tissues mainly liver, brain, kidneys, small intestine and adipose tissue. It is the only known enzyme capable of synthesising glutamine, an amino acid with many critical roles human. It plays an important role in ammonia detoxification, nitrogen balance and pH regulation in the liver (Bioulac-Sage and Rullier, 2009). Moreover, Recent studies have focused on the role of GS in many human cancers including; breast, renal, liver, brain, lung and colorectal (DeBerardinis and Cheng, 2010).
In this regard, the present study aimed to evaluate the clinical utility of serum GS in HCC patients with HCV infection, and to compare its diagnostic performance with that of serum AFP.
This study was conducted on sixty five (65) adult patients positive for HCV by PCR. They will be recruited from the Gastroentrology and Hepatology Department at Ain Shams University Hospitals. The patients will be further classified into: twenty five (25) HCV positive patients with evidence of liver cirrhosis and forty (40) HCV positive patients with established HCC. In addition to fifteen (15) healthy, age and sex-matched persons who are
Summary
142
seronegative for HCV by PCR. All individuals included in this study were subjected to full history taking, thorough clinical examination. Laboratory investigations including: viral markers; HCV RNA by real-time PCR, HBsAg, HBcAb by enzyme linked immunosorbent assay (ELISA), fasting blood sugar, liver profile (AST, ALT, serum bilirubin, total protein, serum albumin, prothrombin time), serum AFP and serum concentration of GS by ELISA. Serum AFP showed non-significant difference between liver cirrhosis patients and control subjects. However, AFP was significantly higher in HCC patients when compared with liver cirrhosis patients and control subjects. Many studies showed that the serum GS was significantly higher in liver cirrhosis patients when compared to control subjects. Also, serum GS was significantly higher in HCC patients when compared with liver cirrhosis patients and control subjects.
The correlation study between serum GS and AFP in HCC patients and in liver cirrhosis patients revealed a non-significant correlation between serum GS and AFP in both groups.
The clinical utility of AFP and GS in identifying patients with HCC from those with liver cirrhosis was assessed by ROC curve analysis. This revealed that the best
Summary
143
diagnostic cut-off value for AFP was 28 (ng/mL). This gave a diagnostic sensitivity of 77.5%, diagnostic specificity of 84%, negative predictive value of 70%, positive predictive value of 88.7% and diagnostic efficacy of 80% with AUC of 0.752. As for GS, the best diagnostic cut-off value was 35 (nmol/L). This gave a diagnostic sensitivity of 92.5%, diagnostic specificity of 72%, negative predictive value of 85.7%, positive predictive value of 84.1% and diagnostic efficacy of 84.6% with AUC of 0.874.
Combining both markers, AFP at cut-off of 10 ng/mL and GS at cut-off of 35 nmol/L, gave a diagnostic sensitivity of 97.5%, diagnostic specificity of 100%, negative predictive value of 96.2%, positive predictive value of 100% and diagnostic efficacy of 98.5 % with AUC of 0.997