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

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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Development and application of a fluorescence protein microarray for detecting serum alpha-fetoprotein in patients with hepatocellular carcinoma

Journal of International Medical Research ◽

10.1177/0300060516672370 ◽

2016 ◽

Vol 44 (6) ◽

pp. 1414-1423 ◽

Cited By ~ 1

Author(s):

Aiying Zhang ◽

Chengzeng Yin ◽

Zhenshun Wang ◽

Yonghong Zhang ◽

Yuanshun Zhao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Protein Microarray ◽

Characteristic Curve ◽

Alpha Fetoprotein ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Control Subjects ◽

Serum Alpha Fetoprotein ◽

Healthy Control ◽

Fluorescence Protein

Objective To develop a simple, effective, time-saving and low-cost fluorescence protein microarray method for detecting serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC). Method Non-contact piezoelectric print techniques were applied to fluorescence protein microarray to reduce the cost of prey antibody. Serum samples from patients with HCC and healthy control subjects were collected and evaluated for the presence of AFP using a novel fluorescence protein microarray. To validate the fluorescence protein microarray, serum samples were tested for AFP using an enzyme-linked immunosorbent assay (ELISA). Results A total of 110 serum samples from patients with HCC ( n = 65) and healthy control subjects ( n = 45) were analysed. When the AFP cut-off value was set at 20 ng/ml, the fluorescence protein microarray had a sensitivity of 91.67% and a specificity of 93.24% for detecting serum AFP. Serum AFP quantified via fluorescence protein microarray had a similar diagnostic performance compared with ELISA in distinguishing patients with HCC from healthy control subjects (area under receiver operating characteristic curve: 0.906 for fluorescence protein microarray; 0.880 for ELISA). Conclusion A fluorescence protein microarray method was developed for detecting serum AFP in patients with HCC.

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The Postresection Alpha-Fetoprotein in Cirrhotic Patients with Hepatocellular Carcinoma. An Independent Predictor of Outcome

Journal of Gastrointestinal Surgery ◽

10.1007/s11605-013-2433-9 ◽

2014 ◽

Vol 18 (4) ◽

pp. 701-708 ◽

Cited By ~ 7

Author(s):

Marc-Antoine Allard ◽

Antonio Sa Cunha ◽

Aldrick Ruiz ◽

Eric Vibert ◽

Mylène Sebagh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Independent Predictor ◽

Alpha Fetoprotein ◽

Cirrhotic Patients

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A clinical study of lectin-reactive alpha-fetoprotein as an early indicator of hepatocellular carcinoma in the follow-up of cirrhotic patients

Hepatology ◽

10.1002/hep.1840220317 ◽

1995 ◽

Vol 22 (3) ◽

pp. 802-807 ◽

Cited By ~ 121

Author(s):

Katsuya Shiraki ◽

Koujirou Takase ◽

Yukihiko Tameda ◽

Minoru Hamada ◽

Yoshitane Kosaka ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Study ◽

Alpha Fetoprotein ◽

Early Indicator ◽

Cirrhotic Patients

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HEPATOCELLULAR CARCINOMA

The Professional Medical Journal ◽

10.29309/tpmj/2016.23.02.1072 ◽

2016 ◽

Vol 23 (02) ◽

pp. 209-212

Author(s):

Khalil ur Rehman ◽

Dr. Muhammad Samiullah ◽

Sidra Sharif ◽

Saira Farhat

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Size ◽

Tertiary Care ◽

Alpha Fetoprotein ◽

Enzyme Linked Immunosorbent Assay ◽

Care Hospital ◽

Cross Sectional ◽

Liver Cancers ◽

Size Groups ◽

Group B

Background: Hepatocellular carcinoma (HCC) also known as malignanthepatoma, accounts for most of the liver cancers. Alpha fetoprotein (AFP) has been undoubtedlywidely used as a marker for the detection and monitoring of HCC. This study aimed to find thecorrelation of serum alpha fetoprotein and tumor size in HCC in the tertiary care hospital. StudyDesign: This cross sectional descriptive study. Setting: Pathology Department of Allama IqbalMedical College, Lahore (AIMC). Materials and Methods: The study was carried out on 45HCC patients (13 females and 32 males) came to Jinnah Hospital Lahore. Five ml of venousblood was drawn aseptically from anterior cubital vein of patients and added into plain vial toclot. The samples were centrifuged, to get the plasma separated from blood cells. Serum AFPwas measured by using Enzyme linked Immunosorbent Assay technique (ELISA). Results:There were 10 (22.2%), 19 (42.2%), 16 (35.6) cases in AFP group 1,2,3 respectively. While10 (22.2%), 13 (28.8%), 22 (48.8%) cases in tumor size groups A,B,C. Group C with largetumor size got 48.8% raised AFP levels as compared to group B (28.8%) and group A (10%).Conclusion: This study shows there is significant correlation between serum AFP and tumorsize in HCC (r=0.668). Serum AFP progressively increases with tumor size especially in largersize. Although AFP have suboptimal sensitivity but it is still proves a beneficial in early diagnosisand screening of HCC, when used in combination of USG/Imaging technique.

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Effects of thermal ablation on Treg/Th17 in hepatocellular carcinoma of mice

European Journal of Inflammation ◽

10.1177/2058739219832489 ◽

2019 ◽

Vol 17 ◽

pp. 205873921983248

Author(s):

Shengchuan Huang ◽

Nina Qu ◽

Yanming Men ◽

Zhen Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Peripheral Blood ◽

Thermal Ablation ◽

Th17 Cells ◽

Treg Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Group Model ◽

Mrna Levels ◽

Model Group ◽

Tumor Tissues

The study was aimed to explore the possible function of thermal ablation treatment on T helper 17 (Th17) cells and regulatory T (Treg) cells in transplantation of hepatocellular carcinoma in mice. In total, 60 male C57BL/6 mice were divided into control group, model group, and treat group. Flow cytometry was used to detect the frequency of Th17 and Treg cells in peripheral blood. The levels of interleukin (IL)-17, IL-23, IL-10, and transforming growth factor beta (TGF-β) in serum were detected by enzyme-linked immunosorbent assay (ELISA).The levels of IL-17, RORγt, Foxp3, and TGF-β mRNA in tumor tissues were detected by real-time fluorescence quantitative PCR (qRT-PCR). Compared with the model group, tumor size was significantly decreased after thermal ablation treatment. After treatment, the frequency of Th17 cells in peripheral blood was significantly decreased, while the frequency of Treg cells was profoundly increased ( P < 0.05). The levels of IL-17 and IL-23 were significantly downregulated, while IL-10 and TGF-β levels were upregulated ( P < 0.05). IL-17 and RORγt mRNA levels in tumor tissues were significantly decreased ( P < 0.05), and Foxp3 and TGF-β mRNA levels were significantly increased ( P < 0.05). Thermal ablation treatment plays a positive role in the treatment of hepatoma in mice through affecting the imbalance of Th17/Treg cells.

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Coagulation Assays as Diagnostic Markers of Hepatocellular Carcinoma

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646992 ◽

1988 ◽

Vol 60 (03) ◽

pp. 468-470 ◽

Cited By ~ 7

Author(s):

J J Lefrère ◽

J Conard ◽

P Mavier ◽

L Bettan ◽

M Beaugrand ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prothrombin Time ◽

Alpha Fetoprotein ◽

Factor V ◽

Thrombin Time ◽

Vitamin K1 ◽

Normal Value ◽

Coagulation Assays ◽

Cirrhotic Patients ◽

Time Test

SummaryWith the aim of improving the biological diagnosis of hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP) and factor V levels were assayed in 119 patients with HCC and 60 cirrhotic patients without HCC. Among the patients with HCC, increased levels of AFP (>300 ng/ml) and of DCP (>15 mU/ml) vveie ubseived in 36% and 69% of the cases, respectively. None of the 60 patients without TTCC had increased AFP, and one had abnormal DCP; in this patient, DCP level returned to normal value after vitamin K1 injection. No significant correlation was found between increased AFP and DCP, thus indicating that the two tests complement each other for the diagnosis. A factor V level higher than expected from the reduced prothrombin time test of the patient was detected in 50% of patients with HCC and only 7% of those without HCC. No correlation was found between increased factor V and abnormal AFP or DCP The thrombin time, fibrinogen activity to antigen ratio, and polymerization index failed to differentiate between cirrhosis and HCC. We conclude that AFP, DCP and factor V may give complementary informations in the diagnosis of HCC, one of these markers at least being positive in 88% of the patients.

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