الفهرس 
Acknowledgement
Global Epidemiology of HccOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary malignant tumor of liver cells. Disease burden owing to HCC is significantly increasing in recent years. It is currently the fifth most common cancer and the third most common reason for cancer-related mortality worldwide. HCC mainly occurs in a damaged organ; liver cirrhosis as a result of viral hepatitis (hepatitis B virus (HBV) or/and hepatitis C virus infection (HCV)) or chronic alcohol abuse is a major risk factor for development of HCC. The incidence of viral hepatitis is markedly increasing worldwide, which will even enhance the epidemiologic importance of HCC in the near future.
LT has the potential to eliminate HCC and the underlying tumor-generating cirrhosis. It provides the widest possible surgical margin and is, therefore, able to reduce the risk of tumor recurrence. In addition, it restores normal liver function. from an oncological and functional point of view, LT may be the optimal treatment for HCC in cirrhotic patients. However, lifetime need of immunosuppressive therapy with persistent risk of tumor recurrence and significant shortage of adequate donor organs are relevant limitations of this therapeutic option.
The MC have incorporated features of tumor macromorphology, such as size and number of HCC nodules, into the same definition of “early HCC”. Patients with HCC meeting them (one solitary tumor nodule up to a maximum of 5cm or a maximum of 3 HCC nodules and each of them up to a maximum diameter of 3cm, without macrovascular invasion and extrahepatic tumor spread) were demonstrated to achieve excellent long-term survival rates. Therefore, these criteria became worldwide “standard” for patient selection process prior to LT.
With the introduction in 2002 of the Model for End- Stage Liver Disease (MELD) liver allocation system, which allows for prioritization of HCC recipients with tumors meeting Milan criteria, the frequency of LT for HCC has nearly doubled. Despite nationwide adoption of the Milan/University of California, San Francisco (UCSF) radiographic size criteria, HCC recurrence after transplantation remains a significant cause of graft loss and mortality, affecting up to 8% to18% of recipients. This is explained in part by the recognition that radiographic size is only a rough surrogate for the key pathologic characteristics that define tumor biology, including tumor grade, differentiation and vascular invasion.
In this study, we analyze the most important risk factors predicting tumor recurrence after liver transplant. We consider also adding biological criteria of the tumor to the morphological ones in the selection process of the tumors candidate for transplantation.
A retrospective study includes 298 HCC patients underwent liver transplantation at Cleveland Clinic Foundation between 2000 and 2011. Pre, postoperative data collected. Primary end point was tumor recurrence and secondary one was patient survival. All statistics were performed with the SPSS statistical analysis.
As regard tumor recurrence, there were 32 patients (10.7%) included in this study experienced tumor recurrence compared to 266 patients (89.3%) had no recurrence during the follow up period. Mortality rate in this cohort was 19.8% (59 patient).
The overall survival rate was calculated using Kaplan-Meier curve. It was 91.8%, 80.5%, 74.4% at 1year, 3 years and 5 years respectively. The mean survival was 7.5 years with C.I between (6.8-8.1).
Univariate analysis revealed that the most important risk factors predicting tumor recurrence were Milan criteria (P value, 0.025), tumor size (P value 0.000), vascular invasion (P value, 0.000), degree of differentiation (p value, 0.047) and AFP level (P value, 0.008).
Logistic regression analysis was done to identify the most significant factor affecting HCC recurrence using recurrence as dependent factor and all other factors as independent factor, the model showed that patient with pathological vascular invasion carries 4.66 risk of recurrence with significant p value (0.005), together with CT lesion size where patient with higher CT lesion size had a 2.2 risk of recurrence with significant p value (0.003).
Cox regression analysis was done to assess the important factors affecting patients’ survival and it showed that the most single important factor affecting the patient survival was tumor recurrence.
In this study, there is obvious linear relationship between AFP level and both pathological vascular invasion and degree of tumor differentiation.
In a subgroup of patients within Milan and had AFP value less than 200 ng/dl, Recurrence rate was 6.8% in compare to 33.3% in others had AFP value more than 200 ng/dl with significant p value (0.02). from these results, we could consider benefits of adding AFP level as a representative of biological activity of the tumor to the traditional morphological Milan criteria in reducing recurrence rate following transplant and better selection of the patients candidate for transplant in the view of limited organ supply.