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

Serum copper /zinc [cu/zn] ratio as an early detector of heptocellular carcinoma among cases of liver cirrhosis

The present study aimed to assess the role of serum copper/zinc [Cu/Zn] ratio as an early detector of hepatocellular carcinoma [HCC] in cases of liver cirrhosis and for screening cases of HCC as a biomarker for cancer. 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. The viral etiology among the studied cases was as the following: 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. The mean serum level of copper was significantly increased among cases of HCC [113.77 +/- 26.96 mg/dl] than that among cases of liver cirrhosis, which was also significantly higher than that of the controls [89.38 +/- 24.34 mg/dl and 70.38 +/- 19.01 mg/dl respectively]. The mean serum level of zinc showed significant depletion among cases of HCC than that of cirrhotic patients, which was also significantly lower than that of the controls [154.42 +/- 28.86 mg/dl, 180.46 +/- 18.23 and 497 +/- 140.79 respectively], denoting disturbance in trace metals in serum of patients with liver cirrhosis, which may be a cause of neoplastic changes. The mean serum Cu/Zn ratio was significantly higher among cases of HCC than that among cases of liver cirrhosis and the controls [0.76 +/- 0.22, 0.50 +/- 0.17 and 0.15 +/- 0.01 respectively]. Serum alpha-fetoprotein [AFP] among cases of HCC [901.15 +/- 386.46 ng/ml] showed significant elevation than that among cases of liver cirrhosis [70.81 +/- 49.68 ng/ml], which was also significantly higher than that among the controls [10 +/- 2.55 ng/ml]. Elevation in serum levels of AFP was significantly correlated with the elevation in the corresponding serum Cu/Zn ratio among cases of HCC [r = 0.78] and cases of liver cirrhosis [r = 0.65] and this correlation help studying changes in trace metals as biomarkers of cancer. Serum levels of AFP and Cu/Zn ratio were not significantly correlated among the controls [r =0.15]. At a cutoff value of 146 mg/dl serum copper, the maximum cirrhotic patients range, showed sensitivity of 19.23%, specificity of 92.31%, positive predictive value [PPV] 71.43% and negative predictive value [NPN] 52.17%, referring to the high predictive value of serum copper in diagnosis of HCC among cases of liver cirrhosis. At a cutoff value of 0.90 serum Cu/Zn ratio, the maximum range of the Cu/Zn ratio among cirrhotic patients, it showed sensitivity of 23.08%, specificity of 96.15%, PPV of 85.71% and NPV of 55.56% in detection of HCC among cases of liver cirrhosis. At a cutoff value of 500 ng/ml serum alpha-fetoprotein, as a definite diagnostic level of cancer, it showed a sensitivity of 92.31%, specificity of 100%, PPV of 100% and NPV of 92.86%. With respect to the highest range of Cu/Zn ratio among the studied cases of HCC, the cut off value of 220 ng/ml serum alpha-fetoprotein showed a sensitivity of 100%, specificity of 96.15%, PPV of 96.30% and NPV was 100% in diagnosing HCC among cases of liver cirrhosis, denoting that the assessment of Cu/Zn ratio may increase the ability of AFP in diagnosing HCC among cases of chronic hepatitis and liver cirrhosis. This denotes the importance of developing a variety of screening protocols to detect hepatocellular carcinoma [HCC] early in patients with hepatitis B surface antigenemia or chronic hepatitis C and patients with liver cirrhosis [as a risk group for HCC] such as serum copper and Cu/Zn ratio, as being available to many laboratories, inexpensive, not time consuming and non-invasive. Also, attention must be paid to excess intake of zinc as diets or supplements for those patients as a preventive measure for HCC