ABSTRACT
Early detection of hepatocellular carcinoma [HCC] is critical for successful treatment. However, the differential diagnosis between HCC and benign hepatic lesions is sometimes difficult and new biochemical markers for HCC are required. The aim of the work was to assess the usefulness of serum AFP, PIVKA-II and TGF- beta1 in the diagnosis and prognosis of HCC and to evaluate the role of serum VEGF in the prediction of venous invasion and metastasis in HCC patients. This study was conducted on 50 patients who were divided into 4 groups; Group I: 10 patients with liver cirrhosis, Group II: 20 patients with benign hepatic focal lesion [HFL], Group III: 10 HCC patients without metastasis before and after treatment in the form of per-cutaneous alcohol injection, and Group IV: 10 HCC patients presenting with metastasis. Ten apparently healthy subjects were taken as a control group. Patients as well as the control subjects were submitted to the following: A] Full clinical examination, B] Imaging techniques including abdominal ultrasonography and CT scan. Patients with HCC were subjected to bone scan and MRI brain, chest and abdomen to detect distant metastasis, C] Laboratory investigations including: complete liver function tests, prothrombin time and concentration, serological examination for hydatid disease, cytological examination of fluid aspirated from infectious cyst, serodiagnosis of HCV and HBV infection, serological markers including AFP, PIVKA-II, VEGF and TGF- beta1 Lastly, histopathologic examination of liver biopsies obtained from focal lesions of HCC patients. A statistically significant difference in the median serum level of AFP, PIVKA-II, VEGF and TGF- beta1 was found on comparing the HCC groups [with and without metastasis] with the control, benign focal lesions and cirrhotic groups. The median serum PIVKA-II level was significantly lower in the non-metastatic HCC group [16.2 ng/ml] compared to the metastatic group [33.6 ng/ml] [P=0.001]. On the other hand, the median serum VEGF level was significantly higher in the non-metastatic HCC group [2580 pg/ml] compared to that of the C group with distant metastasis [1840 pg/ml] [P=0.008]. There was a significant lowering of median serum level of all parameters in the non-metastatic HCC patients after ablation therapy. A statistically significant negative correlation was observed between serum VEGF and serum PIVKA-II in the non-metastatic HCC group. Regarding sensitivity and specificity of the four serological markers: at a cut-off level of 28 ng/ml, AFP yielded a sensitivity of 80% and a specificity of 97%, at a cut-off level of 12.5 mAU/ml for PIVKA-II, the sensitivity was 80% and the specificity was 97%, VEGF revealed a sensitivity of 96.7% and a specificity of 85% at a cut-off level of 780 pg/nil, and lastly TGF- beta1 yielded a sensitivity of 76.7% and a specificity of 97% at a cut-off level of 32.4 ng/ml. Combination of these markers improved both sensitivity and specificity, as combination of AFP and PIVKA-II yielded a sensitivity of 93.3% and a specificity of 98.2%, and for AFP with TGF- beta1, the sensitivity was 87.5% and the specificity was 99%. Combined determination of serological markers could be used as a highly valuable tool for screening and diagnosis of HCC. They could also be used as prognostic markers hence decreasing the need for more invasive procedures such as liver biopsy