Expression of transforming growth factor B -1 gene in patients with hepato cellular carcinoma

Hepatocellular carcinoma [HCC] is the most common primary malignant tumor of the liver. Liver cirrhosis regardless its etiology is the most powerful risk factor for HCC. Transforming growth factor beta-1 [TGF- beta 1] is an important cytokine involved in cell growth, inflammation and hepatic fibrosis. It's also involved in both tumor promoting and suppressing activities. The aim of this work was to determine the alterations in the expression of TGF - beta 1 in cirrhotic patients with and without HCC and to study TGF - beta 1 gene polymorphisms [C-509 T and leu 10 pro] and their associations with the risk of HCC in cirrhotic patients. This work was done on 15 patients with cirrhosis and 15 patients with HCC on top of cirrhosis, and 10 healthy individuals as control group. Alpha fetoprotein [AFP], abdominal ultrasound, triphasic C.T, liver biopsy and TGF- beta 1 expression were done for all patients and controls. There was statistically significant increase in the level of TGF- beta 1 expression in both cirrhosis and HCC groups as compared to control group with higher level of expression in cirrhotic group than HCC group. The frequency of CC genotype of C-509 T and of Leu/Leu genotypes at codon 10 was higher among patients with HCC than in cirrhotic patients and control. As regards to allelic variations, C and/or Leu allele carriers were at higher relative risk for HCC compared with T and/or Pro allele carriers. There was higher expression level of TGF- beta 1 in patients carrying T or Pro allele whether heterozygous or homozygous than those carrying homozygous C or Leu allele. TGF-beta 1 expression may play a role in the pathogenesis of cirrhosis and HCC. It may also be involved in the progression of cirrhosis to HCC. TGF- beta-1 alleles, C at position - 509 and /or leu of codon 10 may be genetic risk factors for HCC in cirrhotic patients. So frequent screening of such patients for HCC is recommended

Is serum antioxidant vitamins A, E and C and trace metals zinc and sellenium have aprotective effect on the occurrence of hepatocellular carcinoma among cases of liver cirrhosis?

Chronic hepatitis is a relevant clinical problem due to mainly evolution to cirrhosis and its life threatening complications. Liver cirrhosis is associated with decreased activity of the antioxidant enzymes as well as many antioxidant micronutrients and vitamins. The high susceptibility of those patients to develop hepatocellular carcinoma [HCC] may be a consequence of superimposed oxidative stress due to lack of defensive mechanisms in cirrhotic patients. The present study aimed to assess the serum levels of antioxidant vitamins A, E and C and micronutrient trace elements zinc and selenium among cases of HCC and cases of liver cirrhosis, to assess the prooxidant antioxidant status in comparison with normal subjects. It was carried out on 26 cases of liver cirrhosis, 26 cases of HCC on top of liver cirrhosis and 26 normal subjects. The study was conducted at the Tropical Medicine Department, Tanta University Hospital, during the year, 1998. According to viral etiology among the studied cases, HCV was detected in 80.77% of cirrhotic patients and 76.92% of HCC cases. HBV was detected in 19.23% of cirrhotic cases and 23.08% of HCC cases. The mixed HBV and HCV caused 15.38% of cirrhotic patients and a same percent of HCC cases. Serum and liver tissue levels of vitamins A and E showed significant depletion among cases of HCC and liver cirrhosis in comparison to normal subjects. This depletion was significantly more marked among cases of HCC than cases of liver cirrhosis. Serum level of vitamin C showed the same pattern. Also, serum and liver tissue levels of trace metals zinc and selenium showed significant decrease among cases of HCC and liver cirrhosis than the control subjects and this decrease was significantly more marked among cases of HCC. Among cases of HCC, the decrease in serum levels of selenium and vitamin A was significantly correlated with the decrease in the corresponding concentrations in liver tissue, while the decrease in serum levels of vitamin E and zinc showed no significant correlation with that in liver tissue. Among cases of liver cirrhosis and normal subjects, there was no significant correlation between serum and liver tissue levels of vitamins A and E and trace elements zinc and selenium. Malondialdehyde [MDA], which is considered as a reflection of the prooxidant status in cells showed significant elevation in serum of cases with liver cirrhosis in comparison to normal subjects. This elevation was significantly higher among cases of HCC. Elevation of serum levels of MDA was significantly correlated with the reduction in serum levels of vitamins A, E and C and that of zinc among cases of HCC, while this correlation was not significant among cases of liver cirrhosis and normal subjects. This denotes the importance of establishment of preventive measures for viral hepatitis, proper treatment of chronic liver cirrhosis and the importance of preventive dietary approach for the cases of chronic hepatitis and liver cirrhosis as risk group for HCC