الفهرس 
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Abstract
HCV infection is one of the most common causes of chronic liver diseases worldwide. It is estimated that more than 200 million people suffer from chronic hepatitis C, and the long-term impact of HCV infection is highly variable, from minimal changes to chronic hepatitis, extensive fibrosis, and cirrhosis with or without hepatocellular carcinoma (HCC).
Hepatocellular carcinoma (HCC) is ranked globally from third to second cancer and is observed characteristically as a complication of chronic liver disease and the third leading cause of cancer death worldwide. Worldwide, liver cancer stands as the second leading cause of cancer death in men and the fifth in women. Carcinogenesis of hepatocytes is a multifactorial, multistep and complex process and has many characteristics, such as fast infiltrative growth, metastasis in early stage, high malignancy, and poor therapeutic efficacy.
HCC, in its very early stage, is heterogeneous both in terms of liver function (i.e. presence or absence of portal hypertention, MELD score, Child A5 or 6, bilirubin level) and tumor characteristics (i.e. location, AFP values, pathological features, such as micro-vascular invasion, tumor grade and satellitosis). One of the most reliable and widely adopted methods for staging HCC is the Barcelona Clinic Liver Cancer (BCLC) system, which stratifies patients according to the characteristics of the tumour, underlying liver disease and performance status. According to this system, the presence of an asymptomatic single nodule ≤ 2 cm, in the absence of vascular invasion or extra-hepatic disease, and in the presence of well compensated cirrhosis (Child A), has been defined as very early stage HCC (BCLC stage 0).
Patients diagnosed with very early HCC could be offered one of the three potential curative options: liver resection (LR), liver transplantation (LT), and radiofrequency ablation (RFA). Patients undergoing these three treatment strategies show excellent outcome in terms of survival and recurrence compared to those with more advanced tumors.
Alpha-fetoprotein levels, the gold standard diagnostic test for HCC at the present time, might be increased in cases of chronic hepatitis and cirrhosis due injury of the hepatocytes. Unfortunately, AFP serum concentrations do not correlate well with the prognostic values of HCC such as tumor size, stage, or disease progression and ethnic variability may also exist. Furthermore, in some cases of HCC, AFP elevations are not apparent at all.
The relationship between telomerase activity in various types of malignancies as a whole and in hepatocellular carcinomas in particular has been the subject of intensified studies and debate over the past few years. In view of the high cost and limited efficacy of treatment, it would be important to identify clearly those who are at risk of developing HCC at an early stage where potential curative therapy could be offered.
The aim of the present work was to verify the value of telomerase activity in chronic hepatitis C patients induced liver cirrhosis with and without hepatocellular carcinoma as well as, its correlation with Child-Pugh score, AFP and tumor size will be evaluated.
This study was conducted on seventy five subjects classified into three groups; group I consisted of twenty five patients with chronic Hepatitis C (CHC) and liver cirrhosis (LC) without HCC, group II included twenty five patients with HCC on top of chronic HCV induced liver cirrhosis and group III composed of twenty five healthy subjects as controls.
All patients and controls were subjected to the following:
1. Proper and detailed history taking and thorough clinical examination.
2. Routine laboratory investigations including:
A-Complete blood picture.
B- Liver function tests: serum AST and ALT, serum bilirubin, serum albumin, prothrombin time and activity.
C-Renal function tests: blood urea and serum creatinine.
3. Viral markers for hepatitis B (HBs Ag) and hepatitis C (anti-HCV) by ELISA and PCR for HCV-RNA.
4. Estimation of serum AFP level.
5. Detection of telomerase activity.
6. Calculation of RTA.
7. Ultrasound examination of the abdomen.
8. Triphasic CT examination was performed for HCC patients only.
9. group I cirrhotic patients was followed for six months and reevaluated for AFP and TA.
Statistical analysis of data obtained from the present study revealed the following results:
• Telomerase activity was positive in 20% of group I cirrhotic HCV patients and 68% of group II HCC patients.
• The RTA levels were significantly higher in group II HCC patients than in group I cirrhotic HCV patients and in controls.
• In group II HCC patients, the level of RTA was significantly higher in large sized tumors > 3 cm in diameter than smaller ones. Also, RTA was significantly higher in HCC patients with portal vein thrombosis.
• ROC curve analyses showed that the sensitivity/specificity of RTA for HCC were 60%/80% at a cut-off value of 0.85. While, the sensitivity/specificity of AFP for HCC were 68%/60% at a cut-off value of 21.5 ng/ml, which is very much lower than diagnostic value for AFP. If we applied diagnostic levels of AFP the sensitivity drops markedly to 36%.
• Combinations of RTA with AFP level improved the sensitivity/specificity up to 96.0% / 68% with 85% positive predictive value, 94% negative predictive value and 82% efficacy.
• group I cirrhotic patients was followed for six months and reevaluated for AFP and TA. During this period three patients died and six patients developed HCC; 3 of them was positive at base line and increased, 3 was negative at base line, 2 became positive in follow up and one remained negative but RTA increased. So, TA was positive in five out of the six (83.3%) cirrhotic patients who developed HCC, while serum AFP was diagnostic (> 400 ng/ml) only in one out of those six cirrhotic patients (16.6%).
• There was significant increase in the RTA after 6 months of follow up. There was significant positive correlation between RTA before and after 6 months follow up.
• Odds ratio for developing HCC in cirrhotic patients with positive TA is 15 and they are at significantly increased risk of HCC development 4.5 times than those with negative TA (p=0.018).