Detection Rate Of Hepatocellular Carcinoma Research Articles

Serum Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) as a Potential Biomarker for Diagnosis of Hepatocellular Carcinoma.

To evaluate the diagnostic performance of aldo-keto reductase family 1 member B10 (AKR1B10) in a Beijing cohort with hepatocellular carcinoma (HCC). This study included 521 subjects who visited Peking Union Medical College Hospital from June 2017 to May 2023, including 109 cases of HCC, 165 cases of healthy controls, 106 cases of benign liver diseases, and 141 cases of other cancers. Serum AKR1B10 levels were measured and compared across various groups. Diagnostic performances of serum AKR1B10 and other tumor markers were assessed using receiver operator characteristic (ROC) curves. In addition, a subset of HCC patients who underwent surgical resection were recruited for clinical follow-up study. We found that serum AKR1B10 expression was higher in patients with HCC relative to other control groups. The association between serum AKR1B10 and clinical features of HCC was not observed. Serum AKR1B10 showed a high diagnostic performance for HCC, and when combined with AFP, the diagnostic effectiveness was significantly improved. Specifically, serum AKR1B10 showed superior diagnostic effectiveness for AFP-negative HCC. The clinical follow-up study indicated a gradual decrease in serum AKR1B10 after surgery. Our study demonstrated that serum AKR1B10 is a promising biomarker for HCC, and when used in combination with AFP can significantly improve the detection rate of HCC.

Complementary Role of CEUS and CT/MR LI-RADS for Diagnosis of Recurrent HCC.

We retrospectively compared the diagnostic performance of contrast-enhanced ultrasonography (CEUS) and contrast-enhanced computer tomography-magnetic resonance imaging (CT/MRI) for recurrent hepatocellular carcinoma (HCC) after curative treatment. After curative treatment with 421 ultrasound (US) detected lesions, 303 HCC patients underwent both CEUS and CT/MRI. Each lesion was assigned a Liver Imaging Reporting and Data System (LI-RADS) category according to CEUS and CT/MRI LI-RADS. Receiver-operating characteristic (ROC) curves were computed to determine the optimal diagnosis algorithms for CEUS, CT and MRI. The diagnostic accuracy, sensitivity, specificity, and area under the curve (AUC) were compared between CEUS and CT/MRI. Among the 421 lesions, 218 were diagnosed as recurrent HCC, whereas 203 lesions were diagnosed as benign. In recurrent HCC, CEUS detected more arterial hyperenhancement (APHE) and washout than CT and more APHE than MRI. CEUS yielded better diagnostic performance than CT (AUC: 0.981 vs. 0.958) (p = 0.024) comparable diagnostic performance to MRI (AUC: 0.952 vs. 0.933) (p > 0.05) when using their optimal diagnostic criteria. CEUS missed 12 recurrent HCCs, CT missed one, and MRI missed none. The detection rate of recurrent HCC on CEUS (94.8%, 218/230) was lower than that on CT/MRI (99.6%, 259/260) (p = 0.001). Lesions located on the US blind spots and visualization score C would hinder the ability of CEUS to detect recurrent HCC. CEUS demonstrated excellent diagnostic performance but an inferior detection rate for recurrent HCC. CEUS and CT/MRI played a complementary role in the detection and characterization of recurrent HCC.

MRI Features for Predicting Microvascular Invasion and Postoperative Recurrence in Hepatocellular Carcinoma Without Peritumoral Hypointensity.

To identify MRI features of hepatocellular carcinoma (HCC) that predict microvascular invasion (MVI) and postoperative intrahepatic recurrence in patients without peritumoral hepatobiliary phase (HBP) hypointensity. One hundred and thirty patients with HCC who underwent preoperative gadoxetate-enhanced MRI and curative hepatic resection were retrospectively reviewed. Two radiologists reviewed all preoperative MR images and assessed the radiological features of HCCs. The ability of peritumoral HBP hypointensity to identify MVI and intrahepatic recurrence was analyzed. We then assessed the MRI features of HCC that predicted the MVI and intrahepatic recurrence-free survival (RFS) in the subgroup without peritumoral HBP hypointensity. Finally, a two-step flowchart was constructed to assist in clinical decision-making. Peritumoral HBP hypointensity (odds ratio, 3.019; 95% confidence interval: 1.071-8.512; P=0.037) was an independent predictor of MVI. The sensitivity, specificity, positive predictive value, negative predictive value, and AUROC of peritumoral HBP hypointensity in predicting MVI were 23.80%, 91.04%, 71.23%, 55.96%, and 0.574, respectively. Intrahepatic RFS was significantly shorter in patients with peritumoral HBP hypointensity (P<0.001). In patients without peritumoral HBP hypointensity, the only significant difference between MVI-positive and MVI-negative HCCs was the presence of a radiological capsule (P=0.038). Satellite nodule was an independent risk factor for intrahepatic RFS (hazard ratio,3.324; 95% CI: 1.733-6.378; P<0.001). The high-risk HCC detection rate was significantly higher when using the two-step flowchart that incorporated peritumoral HBP hypointensity and satellite nodule than when using peritumoral HBP hypointensity alone (P<0.001). In patients without peritumoral HBP hypointensity, a radiological capsule is useful for identifying MVI and satellite nodule is an independent risk factor for intrahepatic RFS.

Vasorin promotes proliferation and migration via STAT3 signaling and acts as a promising therapeutic target of hepatocellular carcinoma

Abnormal expression of Vasorin (VASN) is related to many types of cancer, but the signaling pathway and mechanism of how VASN contributes to the carcinogenesis of hepatocellular carcinoma (HCC) are poorly understood. Here, we found that VASN was up-regulated in serum/serum exosome and tissues of HCC patients. The expression of VASN in serum improve the detection rate of HCC in alpha-fetoprotein-negative HCC patients. Immunohistochemistry revealed that VASN was highly expressed in HCC tissues and associated with different stages of HCC. Noticeably, when serum VASN combined with α-fetoprotein, the area under the curve (AUC), sensitivity, and specificity of HCC patients compared with healthy patients reached 0.918 (95% CI: 0.869–0.967, P < 0.001), 90.91%, and 90.20%, respectively. VASN knockout HCC cells were obtained by CRISPR/Cas9 and a VASN-specific monoclonal antibody was prepared by hybridoma technology. Knockout of VASN or the addition of VASN-specific monoclonal antibody suppressed the proliferation and migration of HCC. Mechanistically, VASN promote the proliferation and migration of HCC by regulating the phosphorylation of STAT3 and the expression of downstream genes CCND1 and MMP2. In conclusion, our findings suggest that VASN plays a crucial role in the activation of STAT3 signaling pathway in HCC, which is a promising target for the diagnosis and therapy of HCC.

Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study.

Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity. This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017. In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors. This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

Low dose of contrast agent and low radiation liver computed tomography with deep-learning-based contrast boosting model in participants at high-risk for hepatocellular carcinoma: prospective, randomized, double-blind study.

To investigate the image quality and lesion conspicuity of a deep-learning-based contrast-boosting (DL-CB) algorithm on double-low-dose (DLD) CT of simultaneous reduction of radiation and contrast doses in participants at high-risk for hepatocellular carcinoma (HCC). Participants were recruited and underwent four-phase dynamic CT (NCT04722120). They were randomly assigned to either standard-dose (SD) or DLD protocol. All CT images were initially reconstructed using iterative reconstruction, and the images of the DLD protocol were further processed using the DL-CB algorithm (DLD-DL). The primary endpoint was the contrast-to-noise ratio (CNR), the secondary endpoint was qualitative image quality (noise, hepatic lesion, and vessel conspicuity), and the tertiary endpoint was lesion detection rate. The t-test or repeated measures analysis of variance was used for analysis. Sixty-eight participants with 57 focal liver lesions were enrolled (20 with HCC and 37 with benign findings). The DLD protocol had a 19.8% lower radiation dose (DLP, 855.1 ± 254.8mGy·cm vs. 713.3 ± 94.6mGy·cm, p = .003) and 27% lower contrast dose (106.9 ± 15.0mL vs. 77.9 ± 9.4mL, p < .001) than the SD protocol. The comparative analysis demonstrated that CNR (p < .001) and portal vein conspicuity (p = .002) were significantly higher in the DLD-DL than in the SD protocol. There was no significant difference in lesion detection rate for all lesions (82.7% vs. 73.3%, p = .140) and HCCs (75.7% vs. 70.4%, p = .644) between the SD protocol and DLD-DL. DL-CB on double-low-dose CT provided improved CNR of the aorta and portal vein without significant impairment of the detection rate of HCC compared to the standard-dose acquisition, even in participants at high risk for HCC. • Deep-learning-based contrast-boosting algorithm on double-low-dose CT provided an improved contrast-to-noise ratio compared to standard-dose CT. • The detection rate of focal liver lesions was not significantly differed between standard-dose CT and a deep-learning-based contrast-boosting algorithm on double-low-dose CT. • Double-low-dose CT without a deep-learning algorithm presented lower CNR and worse image quality.

Prediction of early recurrence of hepatocellular carcinoma after resection based on Gd-EOB-DTPA enhanced magnetic resonance imaging: a preliminary study.

Early recurrence (ER) after radical resection of hepatocellular carcinoma (HCC) affects the prognosis of patients. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can improve the detection rate of small HCC. This study innovatively introduces a new quantitative index combined with qualitative index to compare the differences in clinical and imaging characteristics between ER and non-ER groups and evaluate the feasibility of Gd-EOB-DTPA-enhanced MRI in predicting ER. A total of 68 patients with HCC confirmed by operation and pathology in the Shandong Cancer Hospital and Institute were included retrospectively. All participants were examined by Gd-EOB-DTPA-enhanced MRI within 3 weeks before surgery. Regular follow-up was performed every 2 months within 1 year after operation. Among them, 18 cases with new lesions were in ER group, and 50 cases without new lesions were in non-ER group. The clinical and imaging data of the 2 groups were collected, and the differences of clinical data and preoperative MRI signs between the ER group and non-ER group were compared. The predictive factors of ER after HCC were analyzed by multivariate logistic regression. The quantitative parameter lesion-to-liver contrast enhancement ratio (LLCER) can predict the pathological grade of HCC (P=0.023). The results of univariate analysis between the ER group and non-ER group showed that there were significant differences in pathological grade (P=0.008), lesion morphology (P=0.011), peritumoral low signal intensity in hepatobiliary phase (HBP) (P<0.001), satellite nodules (P<0.001), and LLCER (P<0.001) between the 2 groups. Multivariate logistic regression analysis showed that HBP peritumoral low signal intensity [odds ratio (OR) =7.214, 95% confidence interval (CI): 1.230-42.312, P=0.029], satellite nodules (OR =9.198, 95% CI: 1.402-60.339, P=0.021), and parameter LLCER value (OR =0.906, 95% CI: 0.826-0.995, P=0.039) were independent predictors of ER of HCC after resection. Preoperative Gd-EOB-DTPA enhanced MRI has important predictive value for early recurrence after radical resection of hepatocellular carcinoma.

PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68 Ga-PSMA-11 PET Using Cyclotron-Produced 68 Ga.

Prostate‐specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68Ga‐PSMA‐11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68Ga‐PSMA‐11 PET was prospectively performed in patients with treatment‐naïve HCC on a digital PET scanner using cyclotron‐produced 68Ga. Uptake was graded qualitatively and semi‐quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA (P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor‐associated neovasculature. Higher tumor grade was associated with PSMA expression (P = 0.012) but there was no association with tumor size (P = 0.14), fibrosis (P = 0.35), cirrhosis (P = 0.74), hepatitis B virus (P = 0.31), or hepatitis C virus (P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10‐5) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = −0.753; P = 1.58 × 10‐6). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68Ga‐PSMA‐11 standardized uptake value: SUVmax (median [range] 9.2 [4.9‐28.4]), SUVmean 4.7 (2.4‐12.7), and tumor‐to‐liver background ratio 2 (1.1‐11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68Ga‐PSMA‐11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.

Predictive Models for HCC Prognosis, Recurrence Risk, and Immune Infiltration Based on Two Exosomal Genes: MYL6B and THOC2.

IntroductionHepatocellular carcinoma (HCC) is a heterogeneous molecular disease with complex molecular pathogenesis that influences the efficacy of therapies. Exosomes play a crucial role in tumorigenesis and poor disease outcomes in HCC.ObjectiveThe aim of this study was to identify the optimal gene set derived from exosomes in HCC with substantial predictive value to construct models for determining prognosis, recurrence risk and diagnosis and to identify candidates suitable for immunotherapy and chemotherapy, thereby providing new ideas for the individualized treatment of patients and for improving prognosis.MethodsWeighted correlation network analysis (WGCNA) and univariate and multivariate Cox PH regression analyses were applied to identify exosome-related signatures in the TCGA and exoRbase databases associated with clinical relevance, immunogenic features and tumor progression in HCC. Cell experiments were performed to further confirm the oncogenic effect of MYL6B and THOC2.ResultsThe models for prognosis and recurrence risk prediction were built based on two exosomal genes (MYL6B and THOC2) and were confirmed to be independent predictive factors with superior predictive performance. Patients with high prognostic risk had poorer prognosis than patients with low prognostic risk in all HCC datasets, namely, the TCGA cohort (HR=2.5, P<0.001), the ICGC cohort (HR=3.15, P<0.001) and the GSE14520 cohort (HR=1.85, P=0.004). A higher recurrence probability was found in HCC patients with high recurrence risk than in HCC patients with low recurrence risk in the TCGA cohort (HR=2.44, P<0.001) and the GSE14520 cohort (HR=1.54, P=0.025). High prognostic risk patients had higher expression of immune checkpoint genes, such as PD1, B7H3, B7H5, CTLA4 and TIM3 (P<0.05). Diagnostic models based on the same two genes were able to accurately distinguish HCC patients from normal individuals and HCC from dysplastic nodules.ConclusionOur findings lay the foundation for identifying molecular markers to increase the early detection rate of HCC, improve disease outcomes, and determine more effective individualized treatment options for patients.

Screening, clinical features and prognostic analysis of liver cirrhosis-related hepatocellular carcinoma

Objective To explore the impact of the screening interval and methods on cirrhosis-related hepatocellular carcinoma (HCC) detection and to analyse the clinical features and prognosis of HCC. Materials and methods We recruited 3000 patients diagnosed with liver cirrhosis, who had been treated at the First Affiliated Hospital of Anhui Medical University from January 2016 to January 2020. The time of admission was divided into 3- (group A, 539 cases), 6- (group B, 1012 cases), and 12-month screening groups (group C, 1449 cases). We compared the detection rate of small HCCs in each group and analysed the clinical characteristics and prognosis of the patients with HCC. Results We detected a total of 124 HCC cases, including 41 cases of small HCC: 21, 14, and 6 cases in groups A, B, and C, respectively. The detection rate was 3.9% (21/539) in group A, which was significantly higher than that in groups B and C (χ 2 = 31.186, p < .001). Single small, right liver lobe, and alpha-fetoprotein-negative HCCs accounted for 90.2%, 73.2%, and 68.3%, respectively. We detected vascular invasion and lymph node metastasis in one and three cases, respectively. The average survival time of patients in the small HCC group was significantly higher than that in the non-small-HCC group (35.68 ± 12.95 vs. 22.87 ± 11.42 months) (t = 5.623, p < .001). Conclusions Screening patients with a history of liver cirrhosis at intervals of 3 months can increase the detection rate of small HCCs. Early detection can provide more patients with an opportunity for radical treatment and prolong their survival.

Effectiveness of intraprocedural dual-phase cone-beam computed tomography in detecting hepatocellular carcinoma and improving treatment outcomes following conventional transarterial chemoembolization.

To investigate the effectiveness of intraprocedural dual-phase cone-beam computed tomography (CBCT) in detecting hepatocellular carcinoma (HCC) during conventional transcatheter arterial chemoembolization (TACE) and its effect on improving treatment outcomes. Between November 2018 and November 2019, data from 111 patients with unresectable HCCs (N = 263 lesions) were reviewed retrospectively. All patients had undergone baseline magnetic resonance imaging (MRI) scans within one month prior to the procedure. Both arterial-phase (AP) and delayed-phase CBCT images were acquired during all conventional TACEs. Each HCC detection rate when read by AP-CBCT and when read by dual-phase (DP) CBCT including both AP and delayed phase was compared with that of MRI, and the diagnosis of HCC was based on MRI. Additionally, the follow-up results concerning lipiodol uptake status and tumor response of the lesions detected only by AP-/DP-CBCT were analyzed and compared with MRI-only detected lesions. The overall sensitivity of DP-CBCT (94.7%) was significantly higher than that of AP-CBCT (89.0%) (p = 0.003). In particular, the rate of subcentimeter HCC detection by DP-CBCT was pronounced (91.5% vs. 80.3%) (p = 0.01). Lesions found only by DP-CBCT exhibited positive lipiodol uptake (n = 31/31; 100%) and showed complete or partial responses (n = 24/31; 77.4%) on follow-up CT imaging, while MRI-only detected lesions had less lipiodol uptake (n = 6/14, 42.9%) and complete or partial responses (n = 4/14; 28.6%) (p ≤ 0.001). DP-CBCT imaging during TACE enabled better detection of HCCs than when using AP-CBCT alone, and AP- and DP-CBCT is superior to MRI in detecting chemoembolization-sensitive lesions. This resulted in increased detectability of HCCs and the achievement of better treatment outcomes.

Serum midkine levels for the diagnosis and assessment of response to interventional therapy in patients with hepatocellular carcinoma

ObjectiveTo explore the clinical significance of serum midkine (MDK) levels for the diagnosis of hepatocellular carcinoma (HCC) and evaluate the efficacy of interventional therapy. MethodsEighty-four patients with HCC were enrolled in this retrospective study. They received an interventional treatment. A follow-up was performed every 2 months, using magnetic resonance imaging, to determine whether the treatment should be continued. Serum alpha-fetoprotein (AFP) and MDK levels were measured at the first diagnosis and during the follow-ups, and the HCC detection rates based on the cutoff values of these two measurements were compared. The relationships between AFP and MDK and the clinical tumor characteristics and changes in APK and MDK before and after treatment were also compared using a rank sum test and χ2 test, respectively. The prognostic significance of MDK for HCC was determined through regression analysis. A two-sided P ​< ​0.05 was considered statistically significant. ResultsMDK expression was detected in 95.24% of the cases. Subgroup analysis revealed MDK expression in 95.35%, 95.12%, 85.19%, 86.67%, and 83.33% of the AFP-positive, AFP-negative, stage A Barcelona clinic liver cancer (BCLC-A), BCLC-A/AFP-positive, and BCLC-A/AFP-negative cases, respectively. MDK expression after the interventional treatment (66.7%) was significantly lower than that before the treatment (95.2%). The mean post-treatment MDK level was 0.67 ​ng/mL in patients with a positive response to therapy as compared with 3.66 ​ng/mL in those with no positive response. All patients were followed up for 18 months, and those positive for MDK expression before the intervention were more likely to relapse than patients without MDK expression. Subgroup analysis revealed the highest recurrence rate for patients who were positive for MDK expression before and after treatment. ConclusionsSerum MDK may serve as a powerful complement to AFP in the diagnosis of HCC. MDK measurement may improve the detection rate of BCLC-A and AFP-negative HCC. Serum MDK may help to determine the vascular invasion and poor clinical staging of HCC tumors. Patients with MDK-positive HCC before treatment may be more prone to postoperative tumor progression.

Development and validation of 9-long Non-coding RNA signature to predicting survival in hepatocellular carcinoma.

Primary hepatic carcinoma is 1 of the most common malignant tumors globally, of which hepatocellular carcinoma (HCC) accounts for 85% to 90%. Due to the high degree of deterioration and low early detection rate of HCC, most patients are diagnosed when they are already in the middle and advanced stages, and the prognosis are always poor.RNA sequencing data from the cancer genome atlas was used to explore differences in lncRNA expression profiles. LncRNA was extracted by gdcRNAtools in R package. Multivariate cox analysis was performed on the screened lncRNAs. The relationship between the lncRNA model and prognosis as well as clinical characteristics of patients with HCC was analyzed. Finally, a predictive nomogram in the the cancer genome atlas cohort was established and verified internallyBased on the RNA sequencing survival analysis, a 9- lncRNAs prognosis model, including TMCC1-AS1, AC008892.1, AL031985.3, L34079.2, U95743.1, KDM4A-AS1, SACS-AS1, AC005534.1, LINC01116 was established. The 9-lncRNA prognosis model was a reliable tool for predicting prognosis of HCC, and the nomogram of this prognosis model could help clinicians to choose personalized treatment for HCC patientsThis model was significant to complement clinic characteristics of HCC and to promote personalized management of patients, it also provided a new idea for researches on the prognosis of HCC.

Contrast-enhanced US with Perfluorobutane for Hepatocellular Carcinoma Surveillance: A Multicenter Diagnostic Trial (SCAN).

Background US has served as a standard surveillance tool for hepatocellular carcinoma (HCC); however, the detection rate and false referral rate with this modality are suboptimal. Purpose To evaluate the added value of perfluorobutane-enhanced US when combined with conventional B-mode US as an HCC surveillance tool in participants with liver cirrhosis. Materials and Methods This prospective multi-institution diagnostic trial (https://ClinicalTrials.gov, NCT02188901) used an intraindividual comparison design in a single arm of study participants and was conducted at five referral hospitals. Eligible participants who had liver cirrhosis related to viral hepatitis and were undergoing US for HCC surveillance were enrolled from October 2014 to August 2016. Immediately after completion of B-mode US but before performance of perfluorobutane-enhanced US, operating radiologists entered the results of B-mode US. After completion of subsequent perfluorobutane-enhanced US (Kupffer phase with or without vascular-phase US), the radiologists recorded the results. The presence of HCC was confirmed either with pathologic analysis or radiologically by using dynamic contrast material-enhanced CT or gadoxetic acid-enhanced MRI. The primary end points were the detection rate of early-stage HCC (Barcelona Clinic Liver Cancer staging system stage 0 or A) and false referral rate. The primary end points were compared in a per-participant manner by using the McNemar test. Results A total of 524 participants (mean age, 54 years ± 9 [standard deviation]) were included. Of these, 493 (94.1%) had liver cirrhosis related to the hepatitis B virus. Ten HCCs were confirmed in eight participants. The detection rate of early-stage HCC was not significantly improved by adding perfluorobutane-enhanced US to conventional B-mode US (difference, 0.4% [95% confidence interval: -0.3%, 1.1%]; P = .16). The false referral rate was significantly reduced (difference, -3.2% [95% confidence interval: -5.0%, -1.4%]; P < .001). Conclusion The addition of perfluorobutane-enhanced US to conventional B-mode US reduced the false referral rate without a significant improvement in the detection rate of early-stage hepatocellular carcinoma for surveillance in a population in which the hepatitis B virus predominated. © RSNA, 2019 Online supplemental material is available for this article.

Evaluation of Cytoskeleton-Linking Membrane Protein 63 as a Serum Marker for the Early Detection of Hepatocellular Carcinoma

AbstractBackground: Hepatocellular Carcinoma (HCC) is the third most common cause of cancer death worldwide. The burden of HCC has been increasing in Egypt with a doubling in the incidence rate in the past ten years. Subsequently, novel serum markers are needed to improve the diagnostic accuracy of HCC especially with the low sensitivity of a-Fetoprotein (AFP).Aim of Study: Evaluation of serum Cytoskeleton Linking Membrane Protein-63 (CLIMP-63) as a marker for diagnosis of HCC.Patients and Methods: Eighty individuals were included and they were divided into three groups (30 HCC patients, 30 cirrhotic patients and 20 healthy individuals). Samples were collected and serum CLIMP-63 was determined with Enzyme-Linked Immunosorbent Assays (ELISA). The area under the Receiver Operating Characteristic curve (AuROC), sensitivity and specificity of AFP and CLIMP-63 levels were evaluated for diagnostic performance.Results: Serum CLIMP-63 levels in HCC patients were much higher than healthy individuals and cirrhotic patients (p-value=0.001). The AuROC, sensitivity and specificity of serum CLIMP-63 for the diagnosis of HCC were 0.782, 80% and 68%, respectively. The AuROC, sensitivity and specificity of AFP for the diagnosis of HCC were 0.712, 75% and 70%, respectively.Conclusions: Serum CLIMP-63 may be a novel serum biomarker for diagnosis of HCC in the early stage and testing serum CLIMP-63 and AFP may improve the detection rate of HCC.

B-Mode Ultrasonography versus Contrast-Enhanced Ultrasonography for Surveillance of Hepatocellular Carcinoma: A Prospective Multicenter Randomized Controlled Trial

Background: Current practice guidelines recommend the use of ultrasound (US) as an initial surveillance tool for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. Patients with liver cirrhosis, however, frequently have coarse liver parenchyma, masking the presence of tiny nodules during B-mode US. Contrast-enhanced US (CEUS) with Sonazoid has a long-lasting, stable Kupffer phase, which makes it possible to scan the entire liver to depict small lesions. In addition, defect reperfusion imaging (reinjection imaging) enables to determine whether the detected nodule is HCC or not. This prospective, multicenter, randomized, controlled trial was conducted to demonstrate the usefulness of Kupffer phase surveillance in the detection of small HCC compared to B-mode US. Methods: A total of 23 institutions joined this study. In total, 656 patients with hepatitis B- or C-related liver cirrhosis were randomized either to the B-mode US surveillance group (n = 313) or the Kupffer phase CEUS with Sonazoid surveillance group (n = 309). The primary endpoint was the maximum size of HCC at the time of the first detection. Secondary endpoints included time to HCC detection, number of tumors, and Barcelona Clinic Liver Cancer stage at the first detection, and sensitivity, specificity, and accuracy of each method in the diagnosis, and the cumulative detection rate of HCC. Results: The mean HCC size at the first detection was significantly smaller in the CEUS (13.0 ± 4.1 mm; n = 28) than in the B-mode US group (16.7 ± 4.1 mm; n = 26) (p = 0.011). Of the 38 patients with HCV cirrhosis diagnosed with HCC by US alone, mean tumor size at the first detection was significantly smaller in the 20 patients diagnosed by CEUS alone than in the 18 diagnosed by B-mode US alone (12.7 ± 3.1 vs. 17.6 ± 7.0 mm, p = 0.012). In contrast, among the 16 patients with HBV cirrhosis diagnosed by US alone, mean tumor size at the first detection was similar in the 8 patients diagnosed by CEUS alone and the 8 diagnosed by B-mode US (13.6 ± 6.0 vs. 14.5 ± 2.7 mm, p = 0.715). Conclusion: Kupffer phase CEUS surveillance with Sonazoid is extremely useful for the early detection and confirmation of HCC using a reinjection technique. Kupffer phase CEUS with Sonazoid contrast combined with the reinjection technique is, therefore, recommended as first-line screening tool for HCC in patients with liver cirrhosis, especially those with very coarse liver parenchyma.

Soluble CD25 as a predictor of hepatocellular carcinoma compared with alpha-fetoprotein.

Aim of the studyWe aimed to evaluate soluble CD25 (sCD25) as a marker for hepatocellular carcinoma (HCC) diagnosis.Material and methodsEighty-eight subjects were enrolled in our study in the years 2017-2018. They were divided into three groups as follows: group 1 – HCC group (n = 44) patients, represented by BCLC stage A (n = 16) patients, stage B (n = 14) patients and stage C (n = 14) patients for each stage. All HCC patients were on top of cirrhosis. Group 2 – group of cirrhotic patients without HCC (n = 32); 50% of them were Child-Turcotte-Pugh class A (n = 16) while class B was represented only by 43.7% (n = 14) of patients. Group 3 – control group (n = 12) of healthy subjects.ResultsThe levels of sCD25 and AFP were higher in HCC patients than cirrhotic and control groups without a statistically significant difference between the three groups (p-value > 0.05). For HCC presence, sensitivity and specificity of sCD25 were 86.4% and 29.5% respectively at a cut-off value of 1.1 × 103 pg/ml (AUC = 0.619, p-value = 0.054, PPV = 33.2%, NPV = 68.44%). For early detection of HCC, sCD25 had a sensitivity of 70.5% and a specificity of 30.9% at a cut-off value of 1.575 × 103 pg/ml (AUC = 0.577, p-value = 0.251, PPV = 58.5%, NPV = 43.1%), while the sensitivity and specificity of AFP were 75% and 62.5% respectively at a cut-off value of 9.5 ng/ml (AUC = 0.828, p = 0.000, PPV = 73.4%, NPV = 64.4%) in the same settings.ConclusionssCD25 seems to offer no better detection rate of HCC compared to AFP with lower sensitivity and specificity.

Management of hepatocellular carcinoma: a study on 240 patients in a single referral center

Epidemiology of hepatocellular carcinoma (HCC) is changing globally and trends show an increasing morbidity rates in Northern, Cen­tral and Eastern Europe and North America but a slow decline in Japan, Korea and China. The bur­den of this important complication of chronic advanced liver disease will further increase in the next 10 years. Several reviews focus on a broad spectrum of HCC clinical manage­ment worldwide, including surveillance of patients with cirrhosis thus establishing proper HCC diagnostic and therapeutic options. The study of I. Ivanova et al . involves patient data from a single referral center in St. Marina University Hospital of Varna. It is the first report of the results of a project enti­tled ‘Hepatocellular Carcinoma - a Current Diagnos­tic and Therapeutic Approach`. The study achieves its goal to present the results from this multidisciplinary HCC treatment. This is one of the three largest cohort studies in Bulgaria so far. The paper reports 240 HCC patients during an 11-year period (from 2006 to 2016) in the Clinic of Gastroenterology, St. Marina University Hospital of Varna. These results aim at evaluating the risk factors for HCC and etiology of chron­ic liver disease, the characteristics and severity of underlying liver disease, the methods for HCC diagnosis and tumor burden as well as staging and treatment methods. The analysis of the risk factors for HCC and etiology of chron­ic liver disease shows that chronic hepatitis-B virus (HBV) infection has been registered in 40.4% and chronic hepatitis-C virus (HCV) infection - in 25.8% of HCC patients. There are two cases with HBV/HCV co-infection and four had HBV/hepatitis-D virus (HDV) co-infection. The other rare etiologic factors for chronic liver disease in our cohort are the following: Wilson`s disease in three, autoimmune hepatitis - in two and non-alco­holic fatty liver disease (NAFLD) - in one patient. Unknown etiology has been registered in 28 patients, as 10 of them (36%) have presented with a marker for exposure to HBV (anti-HBc positive antibodies). Despite the common understanding of the link between liver cirrhosis and HCC, only 82% of HCC patients have developed this pathology. HCC is the first complication of chronic liver dis­ease in 2/3 of cases (n=156). One limitation of the study when comparing laboratory results is the lack of similar cohort of patients without malignant transformation. The diagnostic algorithm includes various imaging and biopsy modalities. The primary diagnosis of HCC is based on at least two imaging methods in 133 cases. In any other patients, the imaging method is combined with at least one ultasonography- or computed-tomography-guided biopsy of the he­patic lesions. The pa­tients with very early and early HCC stage account­ for 13% of all HCCs. The treatment modalities encompass every current modality available such as surgical resection (in 23%), radiofrequency ablation (in 5%) and transarterial chemoembolization (TACE) (in 2% of the cases). System­ic therapy, predominantly with Sorafenib, has been intro­duced to 17% of the patients. The significance of ultrasound surveillance in liver cirrhosis patients is confirmed with the large percentage of diagnosed tumors - 51%. In contrast, most HCCs are detected at stage D, mainly due to advance baseline liver cirrhosis. In summary, findings from this study confirm that surveillance with ultrasound and tumor markers like alpha-fetoprotein (AFP) among pa­tients with advanced liver disease may increase HCC detection rate and achieve longer patient survival rate.

Hepatocellular Carcinoma Surveillance: Benefit of Serum Alfa-fetoprotein in Real-world Practice.

IntroductionBetter treatment outcome of early-stage hepatocellular carcinoma (HCC) warrants employment of screening programs, in which ultrasonography (US) and serum alfa-fetoprotein (AFP) have been recommended. Considering cost-effectiveness, serum AFP has recently been withdrawn from several guidelines for HCC surveillance. However, there were limited studies on benefits of AFP for HCC surveillance in Thailand.Materials and methodsThis is a retrospective study of a proportion of HCC cases in which a diagnostic study was triggered by high serum AFP levels, but US failed to detect the lesion. Patients who received diagnostic imaging for HCC at Siriraj Hospital between January 1, 2012 and December 31, 2014 were included. All the patients must fulfill criteria for HCC surveillance according to American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of HCC 2010 or European Association for the Study of the Liver-European Organisation for Research and Treatment of Cancer (EASL-EORTC) Clinical Practice Guidelines: Management of HCC 2012. Previous diagnosis of any liver malignancy was excluded. Demographic data, underlying liver diseases, screening of AFP and US results, and definite diagnosis of HCC were recorded.ResultsOf the 452 cases who fulfilled inclusion and exclusion criteria, chronic hepatitis B, C, and alcoholic cirrhosis were accountable for 53.8, 25.9, and 7.3% respectively. Totally, 150 cases were diagnosed with HCC. Additional HCC detection rate by high serum AFP but failed US of 15.3% was demonstrated. Subgroup analysis revealed significant benefit of AFP in cirrhotic patients with chronic hepatitis B and C (p-value 0.004 and 0.002). No significant benefit was observed in cirrhosis of other causes and in noncirrhotic chronic hepatitis B.ConclusionWe reported a 15.3% additional benefit of serum AFP for HCC surveillance in conjunction with US of liver. Chronic hepatitis B and C with cirrhosis significantly derived the benefit from serum AFP screening.How to cite this article: Lersritwimanmaen P, Nimanong S. Hepatocellular Carcinoma Surveillance: Benefit of Serum Alfa-fetoprotein in Real-world Practice. Euroasian J Hepato-Gastroenterol 2018;8(1):83-87.

Effectiveness of PIVKA-II in the detection of hepatocellular carcinoma based on real-world clinical data

BackgroundProtein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is an efficient biomarker specific for hepatocellular carcinoma (HCC). Some researchers have proved that levels of PIVKA-II reflect HCC oncogenesis and progression. However, the effectiveness of PIVKA-II based on real-world clnical data has barely been studied.MethodsA total of 14,861 samples were tested in Southwest Hospital in over 2 years’ time. Among them, 4073 samples were PIVKA-II positive. Finally, a total of 2070 patients with at least two image examinations were enrolled in this study. Levels of AFP and PIVKA-II were measured by chemiluminescence enzyme immunoassay (CLEIA) and chemiluminescent microparticle Immunoassay (CMIA), respectively.ResultsA total of 1016 patients with HCC were detected by PIVKA-II in a real-world application. In all these cases, 88.7% cases primarily occurred and patients with advanced HCC covered 61.3%. Levels of PIVKA-II were significantly higher in advanced group (4650.0 mAU/ml, 667.0–33,438.0 mAU/ml) than early-stage group (104.5 mAU/ml, 61.0–348.8 mAU/ml; P < 0.001). Levels of PIVKA-II elevated significantly in recurrence and residual group than recovery group (P < 0.001). A total of 1054 PIVKA-II positive patients were non-HCC cases. Among them, cirrhosis took the largest part (46.3%), followed by hepatitis (20.6%) and benign nodules (15.3%). High-levels of PIVKA-II in at-risk patients is an indicator of HCC development in two-year time.ConclusionsOur data showed that PIVKA-II effectively increases the detection rate of HCC was a valid complement to AFP and image examination in HCC surveillance.