Alpha-1 Antitrypsin and Hepatocellular Carcinoma in Liver Cirrhosis: SERPINA1 MZ or MS Genotype Carriage Decreases the Risk

Heterozygotes for Z or S alleles of alpha-1-antrypsin (AAT) have low serum AAT levels. Our aim was to compare the risk of hepatocellular carcinoma (HCC) in patients with liver cirrhosis carrying the SERPINA1 MM, MZ and MS genotypes. The study groups consisted of 1119 patients with liver cirrhosis of various aetiologies, and 3240 healthy individuals served as population controls. The MZ genotype was significantly more frequent in the study group (55/1119 vs. 87/3240, p < 0.0001). The MS genotype frequency was comparable in controls (32/119 vs. 101/3240, p = 0.84). MZ and MS heterozygotes had lower serum AAT level than MM homozygotes (medians: 0.90 g/L; 1.40 g/L and 1.67 g/L; p < 0.001 for both). There were significantly fewer patients with HCC in the cirrhosis group among MZ and MS heterozygotes than in MM homozygotes (5/55 and 1/32 respectively, vs. 243/1022, p < 0.01 for both). The risk of HCC was lower in MZ and MS heterozygotes than in MM homozygotes (OR 0.3202; 95% CI 0.1361–0.7719 and OR 0.1522; 95% CI 0.02941–0.7882, respectively). Multivariate analysis of HCC risk factors identified MZ or MS genotype carriage as a protective factor, whereas age, male sex, BMI and viral aetiology of cirrhosis increased HCC risk.

Download Full-text

Altered glycosylation, expression of serum haptoglobin and alpha-1-antitrypsin in chronic hepatitis C, hepatitis C induced liver cirrhosis and hepatocellular carcinoma patients

Glycoconjugate Journal ◽

10.1007/s10719-016-9658-2 ◽

2016 ◽

Vol 33 (2) ◽

pp. 209-218 ◽

Cited By ~ 12

Author(s):

Gautam Mondal ◽

Ashish Saroha ◽

Partha Pratim Bose ◽

B. P. Chatterjee

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Serum Haptoglobin ◽

Altered Glycosylation ◽

Alpha 1 Antitrypsin

Download Full-text

The role of chemokine CC ligand 20 in patients with liver cirrhosis and hepatocellular carcinoma

The International Journal of Biological Markers ◽

10.5301/jbm.2012.9097 ◽

2012 ◽

Vol 27 (2) ◽

pp. 125-131 ◽

Cited By ~ 8

Author(s):

Hanan H. Soliman ◽

Hala Nagy ◽

Nesreen Kotb ◽

Mohamed A. Alm El-Din

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Predictive Value ◽

Serum Levels ◽

Study Groups ◽

Cross Sectional Study ◽

Cross Sectional ◽

Asymptomatic Patients ◽

Group I

Background and aim To evaluate the role of chemokine CC ligand 20 (CCL20) as a biomarker for hepatocellular carcinoma (HCC). Patients and methods Ninety patients in four groups were enrolled in this prospective cross-sectional study: 30 with HCC (group I), 30 with liver cirrhosis (group II), 15 with hepatitis C virus infection (group III), and 15 healthy blood donors as controls. Alpha fetoprotein (AFP), CCL20 and vascular endothelial growth factor (VEGF) were measured in all groups. Results Serum levels of CCL20 were significantly different among the study groups (F=230.979, p<0.001). The highest level was found in HCC patients (57.305 ± 6.386 pg/mL) followed by patients with cirrhosis (45.999 ± 5.165 pg/mL) compared with 22.781 ± 5.986 pg/mL and 18.585 ± 3.554 pg/mL in asymptomatic patients with HCV infection and controls, respectively. In HCC patients, CCL20 significantly correlated with VEGF (r=0.559, p=0.001), AFP (r=0.814, p<0.001), Child score (r=0.748, p<0.001), and tumor size (r=0.825, p<0.001). The cutoff value of CCL20 for the detection of HCC in HCV-infected patients was 54 pg/mL with 93.1% accuracy, 89.6% negative predictive value, 92.6% positive predictive value, 83.3% sensitivity, and 93.3% specificity. In patients with cirrhosis, CCL20 significantly correlated with VEGF (r=0.455, p=0.011), AFP (r=0.975, p<0.001), and Child score (r=0.977, p<0.001). Conclusion CCL20 may be used for the detection of HCC in HCV-infected patients with comparable specificity and higher sensitivity than AFP.

Download Full-text

Linkage Specific Fucosylation of Alpha-1-Antitrypsin in Liver Cirrhosis and Cancer Patients: Implications for a Biomarker of Hepatocellular Carcinoma

PLoS ONE ◽

10.1371/journal.pone.0012419 ◽

2010 ◽

Vol 5 (8) ◽

pp. e12419 ◽

Cited By ~ 87

Author(s):

Mary Ann Comunale ◽

Lucy Rodemich-Betesh ◽

Julie Hafner ◽

Mengjun Wang ◽

Pamela Norton ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Cancer Patients ◽

Alpha 1 Antitrypsin

Download Full-text

Study of Serum Soluble Programmed Death Ligand 1 as a Prognostic Factor in Hepatocellular Carcinoma in Egyptian Patients

Current Cancer Drug Targets ◽

10.2174/1568009619666190718141647 ◽

2019 ◽

Vol 19 (11) ◽

pp. 896-905 ◽

Cited By ~ 6

Author(s):

Fatma El-Gebaly ◽

Sabry Abou-saif ◽

Mahmoud Elkadeem ◽

Amal Helmy ◽

Sherief Abd-Elsalam ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Vascular Invasion ◽

Study Groups ◽

Prognostic Indicator ◽

High Serum ◽

Soluble Form ◽

Tumor Immune Evasion ◽

Programmed Death ◽

Increased Risk

Background: The expression of programmed cell death ligands on tumor cells has a role in the suppression of antitumor immunity, resulting in tumor immune evasion. Objective: In this study, we evaluated the prognostic value of the soluble form of programmed death-ligand1 (sPD-L1) in Egyptian hepatocellular carcinoma (HCC) patients. Methods: This prospective cohort study was performed between November 2016 to November 2018 on 85 individuals (25 HCC patients, 25 HCC with vascular invasion and/or extrahepatic metastasis, 25 patients with liver cirrhosis, 10 healthy controls). The levels of sPD-L1 were determined in all subjects and compared in different groups and stages of cirrhosis and HCC. The association between sPD-L1 levels and overall survival (OS) was assessed. Results: Significant statistical difference in sPD-L1 was detected between different study groups. The cut-off value for normal sPD-L1 was defined by high sPD-L1 levels determined in a healthy control cohort. It was 2.522 ng/ml. In HCC patients, cut-off value was 7.42 ng/ml (sensitivity 88%, specificity 100%). In HCC with vascular invasion or metastasis, cut–off value was 9.62 ng/ml (sensitivity 88%, specificity 88%). Patients with high serum sPD-L1 or serum bilirubin concentrations had an increased risk of mortality. Conclusion: High sPD-L1 level could be a possible prognostic indicator for a poor outcome in liver cirrhosis and HCC patients. The predictive value of sPD-L1 levels for a successful anti- PD1/PD-L1 therapy should be investigated in the future.

Download Full-text

DIAGNOSTIC PERFORMANCE OF PIVKAII AND NEW POTENTIAL SERUM BIOMARKERS GP3, CSTB, SCCA1 AND HGF FOR DIAGNOSIS OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH ALCOHOLIC LIVER CIRRHOSIS

10.26226/morressier.57c5383fd462b80296c9c970 ◽

2016 ◽

Author(s):

Ivica Grgurevic

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Diagnostic Performance ◽

Serum Biomarkers ◽

Alcoholic Liver Cirrhosis

Download Full-text

Surgical Stages of Liver Cirrhosis In Patients With Hepatocellular Carcinoma

Case Medical Research ◽

10.31525/ct1-nct04076631 ◽

2019 ◽

Author(s):

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis

Download Full-text

The APAC Score: A Novel and Highly Performant Serological Tool for Early Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

Journal of Clinical Medicine ◽

10.3390/jcm10153392 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3392

Author(s):

Joeri Lambrecht ◽

Mustafa Porsch-Özçürümez ◽

Jan Best ◽

Fabian Jost-Brinkmann ◽

Christoph Roderburg ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

At Risk ◽

Liver Cirrhosis ◽

Early Stage ◽

Treatment Options ◽

Growth Factor Receptor ◽

Serum Samples ◽

Disease Etiology ◽

Risk Patients ◽

Scoring Tool

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.

Download Full-text