Hepatitis C virus (HCV)-cirrhotic patients have the highest threat of developing hepatocellular carcinoma (HCC) and may be at risk of extra hepatic cancer. The present study was designed to investigate CD133 and CK19 in HCV (genotype-4)-cirrhotic patients with/without HCC or extra hepatic cancer, to assess the degree of their correlation with cell cycle abnormalities and finally to assess the role of their combination as diagnostic tool for discrimination of cirrhotic patients with HCC from those with extra hepatic cancer. The study included 77 HCV-cirrhotic patients and 20 healthy non-disease control group. Patients were categorized histo-pathologically into: 24 have only liver cirrhosis, 26 with HCC, and 27 patients with extra hepatic cancer. Cell cycle abnormalities, CD133 and CK19 were determined by flow cytometry technique. CD133 and CK19 showed marked elevation in HCC and extra hepatic cancer compared with liver cirrhosis and control subjects (p<0.0001). Positive associations were noted between CK19, CD133 and G2/M. They were gradually increased with progression from liver cirrhosis to HCC. Combination of the three showed the best AUC (0.978) and accuracy (92.5%) for discrimination of HCC from extra hepatic cancer. Combined CD133 with G2/M and CK19 comprises an excellent diagnostic panel for discrimination of HCV-cirrhotic patients with HCC from those with extra hepatic cancer.

Background Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, so we should be concerned and look for effective/less-harmful treatments than chemotherapeutics already clinically in application. Aspirin works well ''in conjunction'' with other therapies for HCC since aspirin can boost the sensitivity of anti-cancer activity. Vitamin C also was shown to have antitumor effects. In this study, we examined the anti-HCC activities of synergistic combination (aspirin and vitamin C) vs. doxorubicin on HCC-bearing rats and hepatocellular carcinoma (HepG-2) cells. Methods In vitro, we evaluated IC50 and selectivity index (SI) using HepG-2 and human lung fibroblast (WI-38) cell lines. In vivo, four rat groups were used: Normal, HCC (intraperitoneally (i.p.) administered 200 mg thioacetamide/kg/twice a week), HCC + DOXO (HCC-bearing rats i.p. administered 0.72 mg doxorubicin (DOXO)/rat/once a week), and HCC + Aspirin + Vit. C (i.p. administered vitamin C (Vit. C) 4 g/kg/day after day concomitant with aspirin 60 mg/kg/orally day after day). We evaluated biochemical factors [aminotransferases (ALT and AST), albumin, and bilirubin (TBIL) spectrophotometrically, caspase 8 (CASP8), p53, Bcl2 associated X protein (BAX), caspase 3 (CASP3), alpha-fetoprotein (AFP), cancer antigen 19.9 (CA19.9), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) using ELISA], and liver histopathologically. Results HCC induction was accompanied by significant time-dependent elevations in all measured biochemical parameters except the p53 level significantly declined. Liver tissue architecture organization appeared disturbed with cellular infiltration, trabeculae, fibrosis, and neovascularization. Following drug medication, all biochemical levels significantly reversed toward normal, with fewer signs of carcinogenicity in liver tissues. Compared to doxorubicin, aspirin & vitamin C therapy ameliorations were more appreciated. In vitro, combination therapy (aspirin & vitamin C) exhibited potent cytotoxicity (HepG-2 IC50 of 17.41 ± 1.4 µg/mL) and more excellent safety with a SI of 3.663. Conclusions Based on our results, aspirin plus vitamin C can be considered reliable, accessible, and efficient synergistic anti-HCC medication.