Diagnosis Of Hepatocellular Carcinoma In Patients Research Articles

Utilization of Biopsy-Guided CT Scan in Diagnosing Liver Cancer: A Case Study

Introduction: Liver cancer is one of the most common types of cancer in Indonesia and has a high mortality rate. Early diagnosis of liver cancer is very important to increase the patient's chances of recovery. Biopsy-guided CT scan is an effective method for diagnosing liver cancer.
 Case presentation: We report the case of a 55 year old man with a history of chronic hepatitis B who presented with complaints of right upper abdominal pain and weight loss. Physical examination revealed hepatomegaly and ascites. Investigations, including abdominal ultrasound and liver function tests, showed a mass in the liver. CT scan of the abdomen with contrast showed a hypodense mass in the right hepatic lobe. A CT-guided liver biopsy was performed and the histopathological diagnosis was hepatocellular carcinoma (HCC). The patient then underwent partial resection hepatectomy and chemotherapy.
 Conclusion: Biopsy-guided CT scan is a valuable tool for the diagnosis of HCC in patients with chronic hepatitis B.

Study for the Significance of Osteopontin vs Alpha Feto Protein as a Diagnostic Marker for Hepatocellular Carcinoma in Cirrhotic Patients with HCV

Abstract Background Outcome of hepatocellular carcinoma (HCC) depends mainly on its early diagnosis. The performance of traditional biomarkers is not satisfactory. Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. Several studies have reported that osteopontin (OPN) is a promising marker for the diagnosis of hepatocellular carcinoma (HCC); however, some studies emerged with conflicting results, Aim of the Work To evaluate the clinical significance of the plasma osteopontin (OPN) versus alpha-fetoprotein (AFP) in the diagnosis of HCC in cirrhotic patients Patients and Methods This study was Case-Control study, was conducted at internal Medicine and Gastroenterology outpatient clinics and ward in Ain Shams University Hospitals on Patients divided into 3 groups: (Group 1): 50 patients with previously diagnosed HCC on top of chronic HCV induced cirrhosis, (Group II): 15 chronic HCV patients with cirrhosis, (Group III):15 healthy controls during a period of Six months Results There was high statistically significant difference between the studied groups as regard OPN and AFP, Conclusion Plasma OPN level was elevated in the HCV-related HCC patients by comparison to the chronic HCV patients with cirrhosis and healthy controls. OPN is a promising tumor marker that could be added to the current standard tests for the diagnosis of HCC in patients with liver cirrhosis, due to Chronic HCV infection, in order to detect the disease at an early stage and, hence, improve the prognosis and survival rates of these patients

A preliminary discussion on carnosine dipeptidase 1 as a potential novel biomarker for the diagnostic and prognostic evaluation of hepatocellular carcinoma

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

Hepatocellular carcinoma presenting as a chest wall mass - An unusual case diagnosed on cytology with review of literature.

Hepatocellular carcinoma (HCC) is associated with an aggressive behavior and a strong tendency for extrahepatic metastasis. Although 5%-15% patients have metastases at diagnosis, presentation with symptoms exclusively related to extrahepatic metastases is rare. An 82-year-old male presented with an isolated left anterolateral chest wall swelling. Ultrasonography revealed a soft tissue mass involving the anterior chest wall with adjacent rib erosion. Serum protein electrophoresis showed increase in beta-2 region. A clinical diagnosis of multiple myeloma was considered. Fine needle aspiration cytology from the swelling showed loosely cohesive clusters of polygonal cells with traversing blood vessels. Cells showed abundant vacuolated to granular cytoplasm, round nuclei with frequent intranuclear cytoplasmic inclusions. A differential of metastatic HCC and renal cell carcinoma was considered. Subsequent imaging showed a 12 cm mass in the liver. Biopsy from chest wall mass with immunohistochemistry confirmed the diagnosis. Lungs and lymph nodes are the commonest sites for metastatic HCC; presentation as chest wall metastasis is rarely reported. The classical cytomorphology of HCC proved useful in diagnosing metastasis at a rare site. Recent studies have shown that beta-2-globulin is a promising biomarker for early diagnosis of HCC in patients with chronic liver disease.

Real world impact of hepatocellular carcinoma stage and hepatic function on health-related quality of life.

e16215 Background: Health-Related Quality of Life (HRQoL) is an important prognostic indicator and clinical endpoint for patients with hepatocellular carcinoma (HCC). The relationship between cancer stage, liver function, performance status, and HRQoL in HCC in a real-world clinical setting is not well defined. Methods: A retrospective chart review was undertaken of consecutive patients with HCC treated at our institution's liver multidisciplinary clinic between February 2020 and August 2022. We examined the relationship between Barcelona Clinic Liver Cancer (BCLC) stage, Child Pugh (CP) score, and Eastern Cooperative Oncology Group (ECOG) performance status on HRQoL at diagnosis. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. Results: Fifty-one patients met our inclusion criteria. The median age was 69 and the mean FACT-Hep score was 130.3 ± 20.3. FACT-Hep total and subscales showed no significant association with BCLC stages A, B, and C (p =0.224), except in the Emotional Well Being (EWB) subscale (p =0.001). There was no impact of ECOG performance status on the FACT-Hep scores, except for the Functional Well Being (FWB) subscale (p=0.006). Patients with a CP B had significantly more impairment in FACT-Hep than patients with CP A, including FACT-Hep total score (118.5 ±27.3 versus 134.3 ±23.8; p =0.021) and subscales including the Physical Well Being (p =0.018), FWB (p =0.030), Hepatobiliary Cancer Subscale (p &lt;0.001), and FACT-Hep Trial Outcome Index score (p =0.003). Conclusions: Cancer stage poorly correlates with HRQoL at diagnosis in HCC patients. Impaired liver function reduces overall quality of life in HCC patients. Further large-scale prospective studies should be undertaken which incorporate validated HRQoL tools in the routine assessment of HCC patients. [Table: see text]

Assessment of Serum Aldo-Keto Reductase Family 1 Member B10 for Early Diagnosis of Hepatocellular Carcinoma Patients in Suez Canal University Hospital, Egypt ‎

Assessment of Serum Aldo-Keto Reductase Family 1 Member B10 for Early Diagnosis of Hepatocellular Carcinoma Patients in Suez Canal University Hospital, Egypt ‎

A novel predictive model of microvascular invasion in hepatocellular carcinoma based on differential protein expression

BackgroundThis study aims to construct and verify a nomogram model for microvascular invasion (MVI) based on hepatocellular carcinoma (HCC) tumor characteristics and differential protein expressions, and explore the clinical application value of the prediction model.MethodsThe clinicopathological data of 200 HCC patients were collected and randomly divided into training set and validation set according to the ratio of 7:3. The correlation between MVI occurrence and primary disease, age, gender, tumor size, tumor stage, and immunohistochemical characteristics of 13 proteins, including GPC3, CK19 and vimentin, were statistically analyzed. Univariate and multivariate analyzes identified risk factors and independent risk factors, respectively. A nomogram model that can be used to predict the presence of MVI was subsequently constructed. Then, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were conducted to assess the performance of the model.ResultsMultivariate logistic regression analysis indicated that tumor size, GPC3, P53, RRM1, BRCA1, and ARG were independent risk factors for MVI. A nomogram was constructed based on the above six predictors. ROC curve, calibration, and DCA analysis demonstrated the good performance and the clinical application potential of the nomogram model.ConclusionsThe predictive model constructed based on the clinical characteristics of HCC tumors and differential protein expression patterns could be helpful to improve the accuracy of MVI diagnosis in HCC patients.

CEUS LI-RADS for diagnosis of hepatocellular carcinoma in individuals without LI-RADS-defined hepatocellular carcinoma risk factors

PurposeThis study evaluated the performance of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) in patients without LI-RADS-defined hepatocellular carcinoma (HCC) risk factors (RF−).MethodsPatients with LI-RADS-defined HCC risk factors (RF+) and RF− were enrolled in a retrospective study. Additionally, a prospective evaluation in the same centre was performed as a validation set. The diagnostic performances of the CEUS LI-RADS criteria in RF+ and RF− patients were compared.ResultsOverall, we included 873 patients in the analyses. In the retrospective study, the LI-RADS category (LR)-5 specificities for diagnosing HCC did not differ between the RF+ and RF− groups (77.5% [158/204] vs 91.6% [196/214], P = 0.369, respectively). However, the positive predictive value (PPV) of CEUS LR-5 was 95.9% (162/169) and 89.8% (158/176) in the RF+ and RF− groups, respectively (P = 0.029). In the prospective study, the PPV of LR-5 for HCC lesions was significantly higher in the RF+ group than in the RF− group (P = 0.030). The sensitivity and specificity did not differ between the RF+ and RF− groups (P = 0.845 and P = 0.577, respectively).ConclusionsThe CEUS LR-5 criteria shows clinical value for diagnosis of HCC in patients with and without risks.

Blood-Based Biomarkers in Afp Normal/Stable Hepatocellular Carcinoma: Diagnostic and Prognostic Relevance of Mir-10b for Patients on Liver Transplant List

As a diagnostic criteria of hepatocellular carcinoma (HCC), the exact threshold of alpha-fetoprotein (AFP) is controversial. In additional, not all HCC tumors are AFP positive or secrete elevated amounts of AFP into the serum. However, the diagnosis of HCC is quite important on the liver transplant list. Therefore, the purpose of this study was to investigate the expression of circulating micro RNAs (miRNAs) in AFP-stable HCC patients. Thus, we aimed to determine a diagnostic biomarker in these patients. Sixteen miRNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction system in AFP-stable HCC and AFP-trending HCC patients. In our study, 46.7% (n=28) of the patients diagnosed with HCC had stable/normal AFP levels. We detected that high expression of miR-24, miR-10b and the low expression of miR-143 were independently and significantly associated with HCC in AFP-stable compared with AFP trending (P < .05). Additionally, we demonstrated that the overexpression of miR-10b was associated with poor disease-free survival in HCC (P=0.001). Although more clinical validations are needed for the diagnosis of HCC, our current results indicate that the coexistence of high expression of miR-10b and miR-24 may help clinicians adjust in the diagnosis of HCC in patients who are on the liver transplant list but awaiting biopsy for the diagnosis of HCC.

Performance of adding hepatobiliary phase image in magnetic resonance imaging for detection of hepatocellular carcinoma: a meta-analysis.

To determine the performance of diagnostic algorithm of adding hepatobiliary phase (HBP) images in Gd-EOB-DTPA-enhanced MRI for the detection of hepatocellular carcinoma (HCC) measuring up to 3 cm in patients with chronic liver disease. We searched multiple databases from inception to April 10, 2020, to identify studies on using Gd-EOB-DTPA-enhanced MRI for the diagnostic accuracy of HCC (≤ 3 cm) in patients with chronic liver disease. The diagnostic algorithm of Gd-EOB-DTPA-enhanced MRI with HBP for HCC was defined as a nodule showing hyperintensity during arterial phase and hypointensity during the portal venous, delayed, or hepatobiliary phases. For gadoxetic acid-enhanced MRI without HBP, the diagnostic criteria were a nodule showing arterial enhancement and hypointensity on the portal venous or delayed phases. The data were extracted to calculate summary estimates of sensitivity, specificity, diagnostic odds ratio, likelihood ratio, and summary receiver operating characteristic (sROC) by using a bivariate random-effects model. Twenty-nine studies with 2696 HCC lesions were included. Overall Gd-EOB-DTPA-enhanced MRI with HBP had a sensitivity of 87%, specificity of 92%, and the area under the sROC curve of 95%. The summary sensitivity of Gd-EOB-DTPA-enhanced MRI with HBP was significantly higher than that without HBP (84% vs 68%, p = 0.01). Gd-EOB-DTPA-enhanced MRI with HBP showed higher sensitivity than that without HBP and had comparable specificity for diagnosis of HCC in patients with chronic liver disease. • Hypointensity on HBP is a major feature for diagnosis of HCC. • Extending washout appearance to the transitional or hepatobiliary phase on Gd-EOB-DTPA provides favorable sensitivity and comparable specificity for diagnosis HCC. • The summary sensitivity of gadoxetic acid-enhanced MRI with HBP was significantly higher than that without HBP (84% vs 68%, p = 0.01) for diagnosis of HCC in patients with chronic liver disease.

Serum N-glycan profiling as a diagnostic biomarker for the identification of hepatitis B virus-associated hepatocellular carcinoma.

Changes in N-glycosylation of proteins are thought to play a key role in cancer. This study aims to investigate the changes in the serum N-glycan profiles of patients with hepatitis B virus (HBV)-related liver disease, and to evaluate the role of N-glycan markers in the noninvasive diagnosis of hepatocellular carcinoma (HCC). Serum samples were available for 21 patients with HCC, 20 patients with liver cirrhosis (LC), 20 patients with chronic hepatitis B (CHB), and 20 healthy subjects. Serum N-glycans were released and analyzed using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Serum AFP was determined by electrochemiluminescence (ECL) (AFP reference value range: <10 ng/mL). There were characteristic changes in the serum N-glycan profiles of patients with HBV-related liver disease, including NA2FB, NA3, and NA3Fb. NA2FB was the most abundant in LC patients, while NA3Fb abundance was the highest in HCC patients. For HCC screening in patients, especially in patients with LC, the sensitive of Log peak 9 (94.4%) and Log (peak 9/peak 7) (88.9%) were better than alpha-fetoprotein (AFP) (33.3-61.1%), and their specificity was similar to that of AFP. The receiver operating characteristic (ROC) curve showed that the accuracy of Log peak 9 (AUC: 0.81±0.07) and Log (peak 9/peak 7) (AUC: 0.87±0.06) was better than that of AFP (AUC: 0.72±0.09), while the accuracy of AFP combined with the above 2 indexes was better than that of a single index. Moreover, Log (peak 9/peak 7) combined with AFP (AUC: 0.89±0.06) had the best accuracy in the diagnosis of HCC. Our research indicates that N-glycan may serve a new, valuable, and noninvasive alternative method for diagnosing HCC, and it may be a supplement to AFP in the diagnosis of HCC in patients with HBV-related liver disease.

Preoperative diagnosis of hepatocellular carcinoma patients with bile duct tumor thrombus using deep learning method

Preoperative diagnosis of bile duct tumor thrombus (BDTT) is clinically important as the surgical prognosis of hepatocellular carcinoma (HCC) patients with BDTT is significantly different from that of patients without BDTT. Although dilated bile ducts (DBDs) can act as biomarkers for diagnosing BDTT, it is easy for doctors to ignore DBDs when reporting the imaging scan result, leading to a high missed diagnosis rate in practice. This study aims to develop an artificial intelligence (AI) pipeline for automatically diagnosing HCC patients with BDTT using medical images. The proposed AI pipeline includes two stages. First, the object detection neural network Faster R-CNN was adopted to identify DBDs; then, an HCC patient was diagnosed with BDTT if the proportion of images with at least one identified DBD exceeded some threshold value. Based on 2354 CT images collected from 32 HCC patients (16 with BDTT and 16 without BDTT, 1∶1 matched), the proposed AI pipeline achieves an average true positive rate of 0.92 for identifying DBDs per patient and a patient-level true positive rate of 0.81 for diagnosing BDTT. The AUC value of the patient-level diagnosis of BDTT is 0.94 (95% CI: 0.87, 1.00), compared with 0.71 (95% CI: 0.51, 0.90) achieved by random forest based on preoperative clinical variables. The high accuracies demonstrate that the proposed AI pipeline is successful in the diagnosis and localization of BDTT using CT images.

The diagnostic value of contrast-enhanced ultrasound LI-RADS for hepatocellular carcinoma in patients with cirrhosis and chronic hepatitis B

To explore the diagnostic value of American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADS) for hepatocellular carcinoma (HCC) in patients with cirrhosis and chronic hepatitis B. A total of 205 patients at high risk of HCC with solitary hepatic nodule were enrolled and retrospectively analyzed. All patients were over 18years old and had a single lesion with a diameter < 50mm. Lesions were categorized according to size and contrast enhancement patterns in the arterial, portal venous and late phases. Diagnostic efficacy of CEUS LI-RADS for HCC, and the rate of non-HCC malignancies in the LR-M class were compared between patients with cirrhosis and chronic hepatitis B. Of all 205 nodules (median nodule size was 34mm), 142 (69.3%) were HCC. Of the 127 (61.9%) LR-5 category nodules, 95.8% (92/96) nodules were corresponded to HCC in cirrhosis, while 61.3% (19/31) nodules were corresponded to HCC in chronic hepatitis B (P = 0.000). Positive predictive value (PPV) of LR-5 category for HCC was 95.8% in cirrhosis and 61.3% in chronic hepatitis B (P = 0.000). More category of LR-4 nodules were proved to be HCC in patients with cirrhosis than chronic hepatitis B (80.0% vs 8.3%, P = 0.000). Of 41 LR-M category nodules, more non-HCC malignancies were found in chronic hepatitis B (76.0%) than that in cirrhosis (25.0%, P = 0.001). The LR-5 category is highly specific for the diagnosis of HCC in patients with cirrhosis. However, LR-5 category nodules require further CT or MRI examination or histological confirmation in patients with chronic hepatitis B for its unsatisfactory PPV for HCC.

Analysis of urine metabolic profile in patients with hepatocellular carcinoma

Objective: To study the changes of urinary metabolic profile, screen metabolic ions characterization with clinical diagnostic value, and a disease differentiation model establishment, in an attempt to help the clinical diagnosis of hepatocellular carcinoma patients. Methods: A case-control study was conducted. Ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) were used to analyze urine samples of 32 patients with hepatocellular carcinoma, 28 patients with liver cirrhosis and 28 healthy persons, respectively. The orthogonal partial least squares discriminant analysis (OPLS-DA) and the principal component analysis (PCA) model were constructed using MZmine2.0 and SIMCA-P + 12.0.1.0 software for preliminary screening of metabolites. The metabolic ions selected in the final test were analyzed by SPSS, and the markers were analyzed and screened by one-way analysis of variance. Finally, the sensitivity and specificity of the selected markers were analyzed by calculating the area under the receiver operating characteristic (ROC) curve. One-way analysis of variance was used to compare quantitative indicators between groups. Results: OPLS-DA model parameters were R2X = 35.3%, R2Y = 86.9%, and Q2 = 72.2%, which had a good identification value. A total of 26 characteristic ions were screened, of which 17 were identified. 14, 19-Dihydroaspidospermatine had a high value in distinguishing healthy person with hepatocellular carcinoma patients, and the area under the receiver operating characteristic curve was higher than 0.9. The area under the ROC curve for distinguishing liver cancer with liver cirrhosis patients was 0.88, which was higher than the ROC curve of alpha-fetoprotein (0.75). Conclusion: Based on the UPLC-MS platform, the PCA and OPLS-DA models were successfully constructed, and the characteristic metabolic ions in the urine were extracted and identified, which has a certain value in assisting clinical screening of hepatocellular carcinoma patients.

Magnetic resonance elastography can predict the development of hepatocellular carcinoma: a meta-analysis and systematic review.

Hepatocellular carcinoma (HCC) has become the third leading cause of cancer-related death worldwide, and its incidence rate is increasing. Magnetic resonance elastography (MRE) can indirectly realize the accurate non-invasive evaluation of liver reserve function in HCC patients. In this study, we aimed to evaluate the effectiveness of MRE in the diagnosis of HCC patients. We searched globally-recognized electronic databases, such as PubMed, EMBASE, China National Knowledge Infrastructure, and Cochrane Central, for relevant literature on MRE prediction of HCC. The diagnostic performance of all studies was quantitatively summarized using a bivariate random effects model including heterogeneity analysis, receiver operating characteristic (ROC) curve, and bias determination. The diagnostic accuracy of MRE for HCC was based on 1,735 patients. The sensitivity (31-100%) was lower than the specificity (81-94%). The overall sensitivity was 64% [95% confidence interval (CI): 46-79%; I2=92.44%], and the overall specificity was 85% (95% CI: 82-88%; I2=67.86%). Limited publication bias was observed in this study, and the sensitivity analysis showed that the study was robust. The results of our meta-analysis show that MRE has moderate sensitivity and excellent specificity in the detection of HCC. MRE can be an effective diagnostic tool for HCC and can provide strong support for the selection of clinical treatment methods and prognostic judgment.

Research progress of serum biomarkers for early screening of hepatocellular carcinoma

The latest research data shows that the cause of death of liver cancer patients ranks third among malignant tumors. The global situation of early detection, early diagnosis and early treatment of liver cancer is severe. Therefore, how to achieve early diagnosis of liver cancer has important clinical significance. At present, alpha-fetoprotein, alpha-fetoprotein-L3 and des-gamma-carboxythrombin are commonly used in the clinical detection of hepatocellular carcinoma; however, their sensitivity cannot meet the diagnostic needs of patients with early liver cancer. With the development of molecular biology techniques such as serum oligosaccharide chains detection, B10, a member of the aldehyde ketone reductase family, microRNAs, circulating tumor cells, DNA methylation, and other novel serum biomarkers, a new option for the early screening and diagnosis of hepatocellular carcinoma patients will be offered.

The diagnostic performance of PIVKA-II in metabolic and viral hepatocellular carcinoma: a pilot study.

Hepatocellular carcinoma (HCC) is a primary liver tumor derived from metabolic or viral chronic hepatitis, with few treatment options in advanced cases. New biomarkers that allow improving diagnosis and staging are widely desired. Here, we aim to evaluate the performance of Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) in combination with α-fetoprotein (AFP), in the diagnosis of HCC in patients with metabolic or viral hepatitis. We enrolled 60 HCC patients (20 metabolic and 40 viral) and 20 healthy subjects (HS) as negative controls. PIVKA-II, AFP, Matrix metalloproteinase-9 (MMP-9) and Fibroblast growth factor (FGF) serum levels were assessed by immunoassays. AFP and PIVKA-II levels were obviously higher in patients than in HS. AFP displayed a better diagnostic performance than PIVKA-II for viral HCC while PIVKA-II was better for metabolic HCC. The combination of the two biomarkers did not improve the discriminating ability. PIVKA-II may be considered an independent predictor of macrovascular invasion from HCC cells and it can be used to better stratify HCC patients and should be evaluated in prospective studies for early detection of advanced HCC in metabolic subjects.

Alteration of contrast enhanced ultrasound (CEUS) of hepatocellular carcinoma in patients with cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS)

Transjugular intrahepatic portosystemic shunt (TIPS) can treat portal hypertensive complications and modifies hepatic hemodynamics. Modification of liver perfusion can alter contrast enhancement dynamics of liver nodules. This study investigated the diagnostic performance of contrast-enhanced ultrasound (CEUS) to diagnose hepatocellular carcinoma (HCC) in cirrhosis with TIPS. In this prospective monocentric observational study, CEUS was used to characterize focal liver lesions in patients at risk for HCC with and without TIPS. Times of arterial phase hyperenhancement (APHE) und washout were quantified. Perfusion-index (PI) and resistance-index (RI) of hepatic artery and portal venous flow parameters were measured via doppler ultrasonography. Diagnostic gold standard was MRI/CT or histology. This study included 49 liver lesions [23 TIPS (11 HCC), 26 no TIPS (15 HCC)]. 26 were diagnosed as HCC by gold standard. Sensitivity and specificity of CEUS to diagnose HCC with and without TIPS were 93.3% and 100% vs. 90.9% and 93.3%, respectively. APHE appeared significantly earlier in patients with TIPS compared to patients without TIPS. TIPS significantly accentuates APHE of HCC in CEUS. CEUS has good diagnostic performance for diagnosis of HCC in patients with TIPS.

Plasma Small Extracellular Vesicles Derived miR-21-5p and miR-92a-3p as Potential Biomarkers for Hepatocellular Carcinoma Screening.

IntroductionLiquid biopsy using circulating microvesicles and exosomes is emerging as a new diagnostic tool that could improve hepatocellular carcinoma (HCC) early diagnosis and screening protocols. Our study aimed to investigate the utility of plasma exosomal miR-21-5p and miR-92-3p for HCC diagnosis during screening protocols.MethodsThe study group included 106 subjects: 48 patients diagnosed with HCC during screening, who underwent a potentially curative treatment (surgical resection or liver transplantation), 38 patients with liver cirrhosis (LC) on the waiting list for liver transplantation, and 20 healthy volunteers. The exosomes were isolated by precipitation with a reagent based on polyethylene glycol and were characterized based on morphological aspects (i.e., diameter); molecular weight; CD63, CD9, and CD81 protein markers; and exosomal miR-21-5p and miR-92a-3p expression levels.ResultsWe first demonstrate that the exosome population isolated with the commercially available Total Exosome Isolation kit respects the same size ranging, morphological, and protein expression aspects compared to the traditional ultracentrifugation technique. The analysis of the expression profile indicates that miR-21-5p was upregulated (p = 0.017), and miR-92a-3p was downregulated (p = 0.0005) in plasma-derived exosomes from HCC subjects, independently from the patient’s characteristics. AUROC for HCC diagnosis based on AFP (alpha-fetoprotein) was 0.72. By integrating AFP and the relative expression of exosomal miR-21-5p and miR-92a-3p in a logistic regression equation for HCC diagnosis, the combined AUROC of the new exosomal miR HCC score was 0.85—significantly better than serum AFP alone (p = 0.0007).ConclusionTogether with serum AFP, plasma exosomal miR-21-5p and miR-92a-3p could be used as potential biomarkers for HCC diagnosis in patients with LC subjected to screening and surveillance.

Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Diagnosing Hepatocellular Carcinoma: Diagnostic Performance and Interobserver Agreement.

To determine the diagnostic performance and inter-reader agreement of the contrast-enhanced ultrasound liver imaging reporting and data system (CEUS-LI-RADS) for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. In this prospective study, CEUS-LI-RADS categories (LR-5 for predicting HCC) were assigned by six blinded readers and compared to the definitive HCC diagnosis in patients with liver cirrhosis per the 2017 China Liver Cancer Guidelines (CLCG). CEUS features were recorded in 96 patients with 96histology-proven lesions. The diagnostic performance of LR-5 was described by the sensitivity, specificity and accuracy. Multi-reader agreement was assessed by using intraclass correlation coefficients (ICC). In cirrhotic patients, the specificity of LR-5 (range: 92.7-100.0 %) was statistically higher than that of CLCG for each reader (range: 28.6-64.3 %). However, the sensitivity (range: 38.6-63.6 %) and accuracy (range: 53.4-70.7 %) were statistically lower in CEUS-LIRADS than in CLCG (sensitivity range: 88.6-100.0 %; accuracy range: 77.6-86.2 %). Only fair to moderate inter-reader agreement was achieved for the CEUS-LI-RADS category (ICC = 0.595) and washout appearance (ICC range: 0.338 to 0.555). Neither nodule-in-nodule nor mosaic architecture was observed more often in HCC (all P > 0.05), with poor inter-reader consistency for both (both ICC < 0.20). CEUS-LI-RADS category 5 has a high specificity but a low accuracy for identifying HCC in high-risk patients. Inter-reader agreement is not satisfactory concerning CEUS-LIRADS category and washout appearance. Moreover, the clinical value of ancillary features favoring HCC is quite limited.