No abstract

Background: Alpha-fetoprotein (AFP), routinely used for diagnosis of hepatocellular carcinoma (HCC), is limited with relatively low sensitivity and high false positivity in HBV-related HCC (HBV-HCC). Thus, an alternative approach was explored to improve specificity/sensitivity for diagnosis of HBV-HCC, using the combination of AFP, inflammatory score, and liver function. Methods: Chronic hepatitis B (CHB) (n = 510) and HBV-HCC (n = 473) patients were identified retrospectively for this study. The diagnostic value of single vs combined biomarkers for HBV-HCC was analyzed, using ROC curve. Results: It was observed that elderliness, male sex, cirrhosis, HBeAg + or no-antiviral therapy, and elevation of ALT, AST, neutrophil-lymphocyte ratio (NLR), and AFP were associated with developing HBV-HCC. However, the cut-off ALT defined by Chinese standard, but not by AASLD, was a risk factor. Interestingly, AFP of HBeAg -HBV-HCC patients without cirrhosis was significantly higher than that of the HBeAg + patients. AUC values for AFP, ALT, AST, or NLR were 0.84 (95% CI: 0.815-0.862), 0.533 (95% CI: 0.501-0.565), 0.696 (95% CI: 0.666-0.725), or 0.684 (95% CI: 0.654-0.713) with optimal cut-off at 7.21 ng/mL, 43 IU/mL, 38 IU/mL, or 2.61, respectively. Combination of AFP with ALT, AST, and NLR improved the diagnostic performance for HBV-HCC, compared to any of the single biomarkers or any other combinations among these patients (except no-cirrhosis). Conclusions: Elderliness, male sex, elevated ALT, AST, NLR, AFP, cirrhosis, HBeAg + , and no-antiviral treatment were independent risk factors for HBV-HCC. AASLD standard of ALT cut-off value may not be suitable for the Chinese population. Regular monitoring of HCC among HBeAgpatients with abnormal AFP may improve the management of HBV-HCC. The diagnostic performance of AFP combined with ALT, AST, and NLR for HBV-HCC was superior to single biomarker or 3058 | DING et al

IL-34 involves in host immunity regulated carcinogenesis. Alpha-fetoprotein (AFP) is related to the development of HCC. We explored if combination of IL-34 and APF could improve the diagnostic value in HBV related hepatocellular carcinoma (HBV-HCC). Serum was obtained from HBV patients or healthy control. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBV-HCC patients. Serum IL-34 and MCSF, or intrahepatic IL-34, MCSF and CD68+ tumor associate macrophages (TAMs) were determined using ELISA or immunohistochemistry. Serum IL-34 was 1.7, 1.3 or 2.3-fold higher in HBV-HCC than that of CHB, HBV related cirrhosis or healthy control, which was inhibited following trans-hepatic arterial chemoembolization (TACE) in HBV-HCC patients. Intra-hepatic IL-34 was higher in HBV-HCC than that of the other three groups. Intra-hepatic IL-34 was associated with high HBV-DNA, HBeAg−, poor differentiation and small tumor size of HBV-HCC patients. Intra-hepatic TAMs in HBV-HCC were increased 1.7 or 1.3-fold, compared to that from CHB or HBV-cirrhosis patients. Intra-hepatic TAMs were associated with high HBV-DNA, high tumor differentiation, small tumor size, abnormal AFP and more tumor number. AFP plus serum IL-34, showed the highest AUC (0.837) with sensitivity (0.632) and highest specificity (0.931), suggesting that AFP plus IL-34 enhances the reliability for prediction of the development of HBV-HCC among CHB patients. Circulating and intra-hepatic IL-34 was upregulated gradually in HBV disease progression from CHB, cirrhosis and HCC. IL-34 may be used as a diagnostic biomarker and potential therapeutic target for the management of HBV-HCC.