Liver cancer is the fifth most common cancer ,the third cause of cancer related death and accounts for 7% of all cancers world wide.HCC represents more than 90% of primary liver cancers and is a major global health problem.
Major risk factors for hepatocellular carcinoma include chronic HBV or HCV infection, alcoholic and nonalcoholic fatty liver disease. Less common causes include hereditary hemochromatosis, alpha1-antitrypsin (α1AT) deficiency, autoimmune hepatitis porphyria and Wilson’s disease. The distribution of these risk factors among patients with hepatocellular carcinoma is highly variable, depending on geographic region and race or ethnic group.
The prognosis of HCC remains poor, and most patients have a 5-years survival rate of less than 5% mainly because of the late diagnosis. So, there is a need for detection methods.
Detailed analysis and characterization of molecular, genetic and epi-genetic events would revolutionize early diagnosis of HCC. Gene and protein expression profiling will allow better screening of different stages of HCC as well as establishment of criteria for targeted therapies.
Multiple studies have been demonstrated that ghrelin and adiponutrin genes polymorphism were associated with liver cirrhosis and susceptibility to HCC.
This study aimed to evaluate the role of ghrelin Arg 51 GIn and Adiponutrin ISo 148 Met gene polymorphism in diagnosis of hepatocellular carcinoma in chronic hepatitis C patients.
In order to achieve this goal, fifty patients confirmed to have HCC, twenty five patients with liver cirrhosis and twenty five control subjects were selected from Hepatology, Gastroenterology and Infectious diseases department, Benha University Hospital during the period from April 2014 to December 2015 after approval of Benha university ethical committee.
All patients included in the study were subjected to full history taking, thorough clinical examination, routine laboratory and radiological investigations. Additionally, molecular study of ghrelin and adiponutrin genes polymorphism was done.
This study revealed that HCC was presented more in males with a male to female ratio 2.12:1 and the mean age of patients with HCC was (57±8.5)year , ranging from (40-75) year. There was no statistically significant difference between the studied groups regarding age and sex.
Abdominal enlargement was the commonest symptom in patients with HCC, whereas jaundice was the commonest sign. Past history of blood transfusion was frequently present in patients with HCC rather than other groups.
According to the laboratory investigations, the mean values of ESR, prothrombin time and AFP were significantly higher in HCC group than in other groups.
Concerning Child classification, the majority of HCC patients were Child class C (46%) followed by Child class A (30%) and (24%) of patients were Child class B. As regard BCLC staging of HCC patients were 42%, 2%, 12%, and 43% in stage A, B, C, and D respectively.
Abdominal ultrasonography to HCC group showed that single hepatic focal lesion in (74%) of patients, right lobe focal lesions in (74%) and hypoechoic lesions in (78%) of them.
Concerning genotypes and alleles frequencies in studied subjects, all were wild-type CC homozygote for the ghrelin rs34911341 polymrphism.
About PNPLA3 polymorphism genotypes, 75 patients had CC, 21 had CG, and 4 had GG. The frequency of HCC was higher for patients with CC genotype (90%), than those with CG genotype (10%) and GG genotype (0%).
A sig¬nificant association between rs738409 and HCC risk were found using multiple different genetic mod¬els: allele model C vs. G, dominant model CC+ CG vs. GG and recessive model CC vs. CG + GG. These results suggest that harboring two cop¬ies of the rs738409 C variant was associated with a high risk of HCC occurrence in comparison with cirrhotic group.
Also the current study demonstrated that rs738409 polymrphism with CC genotype was associated with liver cirrhosis in comparison to control group.
Factors possibly associated with the development of HCC were assessed by univariable regression analysis compared with non HCC group. These factors included age > 50, Smoking, History of bleeding, LL edema, ascites, low platelet count, elevated S.Creatinine, blood Urea, AST, ALT and PT ,(CC) Genotype and C Allele of adiponutrin gene. While by multivariable Binary logistic regression analysis for prediction of HCC only AFP, CC Genotype and C Allele of adiponutrin gene were significant predictors of HCV- related HCC.
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