الفهرس 
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Abstract
I
ncidence of Hepatocellular carcinoma (HCC) has rapidly increased worldwide. HCC is the sixth most common malignancy and the third most common cause of cancer related death. Recent investigations in Egypt have shown the increasing importance of HCV infection in the etiology of liver cancer, estimated to account for 40–50% of cases.
Chronic infection with HCV is the leading cause of end-stage liver disease, HCC and liver-related death in Egypt. Direct-acting antiviral agents for chronic hepatitis C have initiated a revolution in the management and control of this important liver disease with cure rates over 90%.
Highly effective DAA were expected to dramatically decrease HCV related liver disease progression to end-stage liver disease and HCC. In fact, the risk of developing HCC continues to persist in those patients with HCV cirrhosis even after they have achieved SVR. In contrast to these initial observations, several larger studies found different results.
Recent studies have suggested that DAA may accelerate the occurrence of HCC in patients with liver cirrhosis. In contrast to these observations, several larger studies found different results.
Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. The impact of genetic variations on risk of HCC remains largely undefined although hepatocarcinogenesis arises from complex interactions between genetic and environmental factors.
A genome wide association studies (GWAS) study is a type of genetic mapping study design that assesses for evidence of association between genetic variants and heritable traits across the entire genome. In a GWAS, many studies identified the association between the SNP rs17047200 in TLL1 gene and development of HCC in patients who achieved an SVR to treatment for chronic HCV infection.
In this study, we aimed to evaluate the role of genetic polymorphism in development of hepatocellular carcinoma in patients achieving sustained virological response (SVR) after direct acting antiviral drugs (DAA) for HCV.
The study included 100 patients: 59 patients were males and 41 patients were females and the mean age was 56.42±10.45 years. Diabetes mellitus was present in 63 patients. Only 1 patient was child class B and the rest of patients were Child class A. Seventy four patients were given SOF/DACLA and 26 were given SOF/DCLA/RIBA. Patients were divided into 2 groups according to occurrence of HCC after DAA: HCC and non HCC groups.
By comparing baseline demographic and investigational data of the 2 groups we found Patients in HCC group showed significantly higher mean age and INR; significantly higher median total bilirubin, MELD score, liver stiffness and FIB-4 score and significantly higher percentage of male gender and diabetes than those in Non HCC group. While other investigated parameters showed no significant difference.
In addition, there was no significant difference found between the 2 groups regarding the distribution of different TLL1 rs17047200 genotype variants (AA, AT, TT and undetermined). Also, TLL1 rs17047200 genotype variants were not recognized as factors or predictors for early HCC development after SVR with DAA in univariate and multivariate analyses.
Lastly, there was no significant association found between different TLL1 rs17047200 alleles and morphological features or aggressiveness of HCC as portal vein thrombosis, extrahepatic spread, number and size of HCC nodules.
In conclusion, TLL1 genotypes was not associated with early HCC development after viral eradication of HCV related cirrhotic patients who treated with DAA.