Comprehensive clinicopathologic study of alpha fetoprotein‐expression in a large cohort of patients with hepatocellular carcinoma

Abstract Background Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC. Methods A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort. Results The C-index of nomogram1was 0.708 (95%CI: 0.673–0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606–0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690–0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691–0.813; AUC: 0.784, 95%CI: 0.709–0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively. Conclusions Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.

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Ramucirumab in patients with advanced hepatocellular carcinoma and elevated alpha‐fetoprotein: outcomes by treatment‐emergent ascites

Hepatology Research ◽

10.1111/hepr.13638 ◽

2021 ◽

Author(s):

Masatoshi Kudo ◽

Masafumi Ikeda ◽

Peter R. Galle ◽

Tatsuya Yamashita ◽

Richard S. Finn ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Alpha Fetoprotein ◽

Advanced Hepatocellular Carcinoma

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Role of annexin A2 and osteopontin for early diagnosis of hepatocellular carcinoma in hepatitis C virus patients

Egyptian Liver Journal ◽

10.1186/s43066-019-0004-9 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Abd El-Fattah F. Hanno ◽

Fatma M. Abd El-Aziz ◽

Akram A. Deghady ◽

Ehab H. El-Kholy ◽

Aborawy I. Aborawy

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Early Diagnosis ◽

Positive Predictive Value ◽

Negative Predictive Value ◽

Chronic Hepatitis C ◽

Predictive Value ◽

Annexin A2 ◽

Alpha Fetoprotein

Abstract Background Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally. Early stages of hepatocellular carcinoma (0&A) can be treated with curative procedures. The aim of this work was to evaluate the role of annexin A2 and osteopontin for early diagnosis of hepatocellular carcinoma in hepatitis C virus patients. Methods The study was carried out on 80 patients classified into two groups. Group A had 40 chronic hepatitis C patients without hepatocellular carcinoma, while group B had 40 chronic hepatitis C patients with early hepatocellular carcinoma (stages; 0&A). All patients were subjected to thorough history taking, clinical examination, liver function tests, renal function tests, serum alpha-fetoprotein, serum osteopontin, and serum annexin A2. Results Serum alpha-fetoprotein was found to be statistically significantly higher in patients with the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for alpha-fetoprotein for detection of HCC was significant, its diagnostic performance was 0.818* (p < 0.001*), and the cutoff point for predicting the probability for HCC was 6.0 (ng/ml) with sensitivity of 77.50%, specificity of 82.50%, positive predictive value of 81.60%, negative predictive value of 78.6%, and accuracy of 80%. Serum osteopontin was found to be statistically significantly higher in patients from the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for osteopontin was significant, its diagnostic performance was 0.739* (p < 0.001*), the cutoff point was 13.2 (ng/ml) with sensitivity of 65.0%, specificity of 90.0%, positive predictive value of 86.70%, negative predictive value of 72.0%, and accuracy of 77.0%. Serum annexin A2 was found to be statistically significantly higher in patients from the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for annexin A2 was significant, its diagnostic performance was 0.927* (p < 0.001*), the cutoff point was 10.1(ng/ml) with sensitivity of 85.0%, specificity of 85.0%, positive predictive value of 85.0%, negative predictive value of 85.0%, and accuracy of 85.0%. Conclusions Osteopontin had better specificity but lower sensitivity than serum alpha-fetoprotein for early diagnosis of hepatocellular carcinoma. Annexin A2 had better diagnostic sensitivity and specificity than alpha-fetoprotein for early diagnosis of hepatocellular carcinoma.

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Evaluation of serum alpha fetoprotein-L3 as an accuracy novel biomarker for the early diagnosis of hepatocellular carcinoma in Egyptian Patients

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2021.06.020 ◽

2021 ◽

Author(s):

Hassnaa Mohamed Ibrahim ◽

Magdy Zaki Elghannam ◽

Om Ali Yousef Elkhawaga ◽

Ahmed Mohamed Adel El-Sokkary

Keyword(s):

Hepatocellular Carcinoma ◽

Early Diagnosis ◽

Alpha Fetoprotein ◽

Egyptian Patients ◽

Serum Alpha Fetoprotein

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Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients

BMC Gastroenterology ◽

10.1186/s12876-021-01761-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kung-Hao Liang ◽

Ming-Wei Lai ◽

Yang-Hsiang Lin ◽

Yu-De Chu ◽

Chih-Lang Lin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Characteristic Curve ◽

Alpha Fetoprotein ◽

Enzyme Linked Immunosorbent Assay ◽

Interleukin 17 ◽

Medical Need ◽

Tumor Tissues ◽

Resected Tumor ◽

Cirrhotic Patients ◽

A Prospective Study

Abstract Background Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. We aimed to investigate circulatory biomarkers and their optimum combinations in a prospective study. Methods We investigated plasma interleukin 17 (IL-17) concentrations, quantified using enzyme-linked immunosorbent assay (ELISA), for the prediction of HCC in a large cohort of 404 HCC-naïve liver cirrhotic patients regularly followed after recruitment. Additionally, IL-17 in surgically resected tumor tissues were evaluated using immunohistochemistry staining. Results IL-17 was detected in HCC tissues. The IL-17 concentrations in the peripheral blood do not have correlation with an extensive list of 31 common demographic, metabolic and liver function variables in the cohort of liver cirrhotic patients. Furthermore, patients stratified by IL-17 and alpha-fetoprotein (AFP) showed distinctive cumulative incidence of HCC. Imminent HCC, defined here as HCC occurrence within 1 year, can be predicted by IL-17 alone with an area under the receiver operating characteristic curve [AUC] of 0.762 (P = 0.002). An multivariate analysis showed that age, hepatitis C viral infection, AFP and IL-17 were four independent factors associated with imminent HCC (adjusted P = 0.03, 0.041, 0.024 and 0.008 respectively). An explicit risk score (R) combining the concentrations of two plasma biomarkers, AFP and IL-17, achieved a high AUC of 0.933 (95% confidence interval 0.893–0.972, P < 0.001) in predicting imminent HCC, with 100% sensitivity and 79.9% specificity at the optimum cutoff. The score is defined as: $${\text{R}} = (2.6914)*{\text{IL-17}} + (0.3909)*{\text{AFP}} - (0.80812875)*{\text{IL-17}}^{2} + (0.10288876884)*{\text{IL-17}}^{2} *{\text{AFP}}.$$ R = ( 2.6914 ) ∗ IL-17 + ( 0.3909 ) ∗ AFP - ( 0.80812875 ) ∗ IL-17 2 + ( 0.10288876884 ) ∗ IL-17 2 ∗ AFP . Conclusions The circulatory IL-17 concentration is a predictor of subsequent HCC occurrence in liver cirrhotic patients. The combination of AFP and IL-17 is highly effective in predicting imminent HCC within 1 year.

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