Abstract
Background: Hepatocellular carcinoma (HCC) is common and the second leading causes of cancer-related deaths. HCC usually occurs on the basis of chronic liver diseases. At present, the study of iron metabolism in chronic liver diseases was limited to chronic HCV infection, nonalcoholic fatty liver disease, and alcoholic liver disease. This study aimed to investigate the effect of serum iron levels on the progression of chronic HBV infection and the relationship with the prognosis of HBV-related HCC.Methods: A respective study involving 277 healthy individuals as controls (HC), 295 patients with chronic hepatitis B (CHB), 224 patients with HBV-related liver cirrhosis (HBV-related LC), and 586 patients with HBV- related HCC were enrolled in this study. Hematological parameters, HBVDNA and liver biochemistry were analyzed. Child-Pugh grade and BCLC stage of the HBV-related HCC patients were calculated.Results: The serum iron levels were lowest in the HBV- related HCC group as compared with HC, CHB, and HBV-related LC groups (35.07 ± 6.97, 27.37 ± 10.26, 24.53 ± 10.36 vs. 17.90 ± 0.14, P < 0.001). Strikingly, serum iron levels were lowest in HBV- related HCC patients with tumor size more than 10 cm as compared with HBV- related HCC patients with tumor size smaller than 3, 3–5, and 5–10 cm by subgroup analysis (22.12 ± 0.94, 21.44 ± 1.41, 15.65 ± 0.98 vs. 13.36 ± 1.15, P < 0.001). Serum iron levels significantly decreased with worsening Child-Pugh grades and BCLC stages in HBV-related HCC group. In addition, serum iron levels was positively correlated with Retinol-Binding Protein, total bile acid, hemoglobin, and lymphocyte and negatively correlated with white blood cell (WBC) and platelet in HBV- related HCC group. ROC curve analysis showed serum iron levels at 15.1 μmol/L as the optimal cut-off point for determining the survival of HBV-related HCC. By the Cox regression model analysis, serum iron levels <15.1 μmol/l together with higher AFP levels, worse BCLC stages, and larger tumor size showed higher mortality of HBV-related HCC patients (hazard ratio = 2.280, 95% confidence interval, 1.815–2.865; P < 0.001).Conclusions: Serum iron levels affected the progression of chronic HBV infection. The prognosis of HBV- related HCC patients with serum iron levels <15.1 μmol/l together with higher AFP levels, worse BCLC stages, and larger tumor lesion were poor.
Highlights
Iron is an elementary particle for life and is involved in many metabolic processes including cell growth and proliferation
A patient is considered positive for HBV- Hepatocellular carcinoma (HCC) if they have risk factors (HBV infection, cirrhosis) and one of the following: (i) Tumor lesion ≤ 2 cm, positive findings in at least two of four typical imaging studies [dynamic computed tomography (CT), contrastenhanced dynamic magnetic resonance imaging (MRI), contrastenhanced ultrasonography (CEUS), hepatic angiography], or histological confirmation. (ii) Tumor lesion >2 cm, positive findings in at least one of the above-mentioned imaging studies or histological confirmation
Two hundred and ninety-five CHB patients, 224 HBV- related LC patients, 586 HBV- related HCC patients and 277 healthy individuals were included in the present study
Summary
Iron is an elementary particle for life and is involved in many metabolic processes including cell growth and proliferation. More previous researches focus on the relationship between liver iron overload and tumorigenesis and progression of HCC. By studying long-term survival in a cohort of 251 patients with hemochromatosis in 1996, the results showed prognosis of hemochromatosis and most of its complications, including liver cancer, depend on the amount and duration of iron excess (Niederau et al, 1996). Xiong et al demonstrated that the effects of iron overload are associated with the tumorigenesis of lung cancer and growth of lung cancer cells in 2014 (Xiong et al, 2014). Up to date, there are scarce of reports about the relationship between serum iron levels and the progression of chronic HBV infection, and the prognosis of HCC.
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