Objective To evaluate the performance of contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) LR-5 in the diagnosis of hepatocellular carcinoma (HCC). Methods The clinical research reports with the application of CEUS LI-RADS in the diagnosis of HCC were collected from PubMed,Embase,Cochrane Library,CNKI,and Wanfang Data from inception to November 14,2021.Two researchers respectively screened the literature and extracted relevant information.The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was used to evaluate the quality of all the included articles.RevMan 5.4,Meta disc 1.4,and Stata 16.0 were employed to analyze the diagnostic performance of LR-5 for HCC in high-risk patients. Results Twenty original studies were included,involving a total of 6131 lesions,of which 5142 were HCC.The results of meta-analysis showed that the LR-5 in CEUS LI-RADS for diagnosing HCC in the high-risk population had the overall sensitivity of 0.72 (95%CI=0.66-0.77),the overall specificity of 0.93 (95%CI=0.87-0.96),the overall positive likelihood ratio of 9.89 (95%CI=5.31-18.41),the overall negative likelihood ratio of 0.30 (95%CI=0.25-0.37),and the area under the summary receiver operating characteristic curve of 0.88 (95%CI=0.85-0.91).There was heterogeneity among the included studies (I²=95.31,P<0.001).The funnel plot indicated the existence of publication bias (P=0.04). Conclusion The CEUS LI-RADS can effectively diagnose HCC in high-risk patients based on the LR-5 criteria.
Humans ; Carcinoma, Hepatocellular/diagnostic imaging* ; Liver Neoplasms/diagnostic imaging* ; Diagnostic Imaging ; Ultrasonography

PURPOSE: To investigate noninvasive biomarkers for predicting treatment response in patients with locally advanced HCC who underwent concurrent chemoradiotherapy (CCRTx).MATERIALS AND METHODS: Thirty patients (55.5 ± 10.2 years old, M:F = 24:6) who underwent CCRTx due to advanced HCC were enrolled. Contrast-enhanced US (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were obtained before and immediately after CCRTx. The third CEUS was obtained at one month after CCRTx was completed. Response was assessed at three months after CCRTx based on RECIST 1.1. Quantitative imaging biomarkers measured with CEUS and MRI were compared between groups. A cutoff value was calculated with ROC analysis. Overall survival (OS) was compared by the Breslow method.RESULTS: Twenty-five patients were categorized into the non-progression group and five patients were categorized into the progression group. Peak enhancement of the first CEUS before CCRTx (PE1) was significantly lower in the non-progression group (median, 18.6%; IQR, 20.9%) than that in the progression group (median, 59.1%; IQR, 13.5%; P = 0.002). There was no significant difference in other quantitative biomarkers between the two groups. On ROC analysis, with a cutoff value of 42.6% in PE1, the non-progression group was diagnosed with a sensitivity of 90.9% and a specificity of 100%. OS was also significantly longer in patients with PE1 < 42.6% (P = 0.014).CONCLUSION: Early treatment response and OS could be predicted by PE on CEUS before CCRTx in patients with HCC.
Biomarkers ; Carcinoma, Hepatocellular ; Chemoradiotherapy ; Humans ; Magnetic Resonance Imaging ; Methods ; Perfusion Imaging ; Response Evaluation Criteria in Solid Tumors ; ROC Curve ; Sensitivity and Specificity ; Ultrasonography

BACKGROUND/AIMS: Antiviral therapy (AVT) reduces the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). This multicenter retrospective study investigated the effects of AVT and hepatitis B virus (HBV)-related factors on the risk of HCC development in a cohort with heterogeneous HBV status. METHODS: A total of 1,843 patients with CHB from two institutions were included in this study. Ultrasound and laboratory tests, including the α-fetoprotein test, were conducted regularly to detect HCC development. RESULTS: The mean age of our study population (1,063 men and 780 women) was 49.4 years. Cirrhosis was identified in 617 patients (33.5%). During follow-up (median, 42.5 months), 81 patients developed HCC (1.39% per person-year). A total of 645 patients (35.0%) received ongoing AVT at enrollment. Ongoing AVT was not significantly associated with the risk of HCC development (all p>0.05). HBV-related variables (HBV DNA level, hepatitis B e antigen status, and alanine aminotransferase level) were also not significantly associated with the risk of HCC development (all p>0.05). In contrast, cirrhosis was significantly associated with the risk of HCC development, regardless of adjustment (adjusted hazard ratio=4.098 to 7.020; all p<0.05). Cirrhosis significantly predicted the risk of HCC development in subgroups with and without ongoing AVT at enrollment, regardless of adjustment. CONCLUSIONS: Our study showed that cirrhosis, not AVT and HBV-related variables, was associated with HCC development in a cohort of patients with heterogeneous HBV status. Our results may help clinicians apply individualized surveillance strategies according to fibrotic status in patients with CHB.
Alanine Transaminase ; Carcinoma, Hepatocellular ; Cohort Studies ; DNA ; Fibrosis ; Follow-Up Studies ; Hepatitis B virus ; Hepatitis B ; Hepatitis B, Chronic ; Hepatitis ; Humans ; Liver Cirrhosis ; Liver ; Male ; Retrospective Studies ; Ultrasonography

Contrast-enhanced ultrasonography (CEUS) using microbubble ultrasonography contrast agent can show the vascular structure and unique contrast enhancement patterns of focal liver lesions, including hepatocellular carcinoma (HCC). CEUS shows three phases, similar to a vascular pattern on computer tomography (CT), and typical arterial enhancement and portal or late phase washout in HCC. CEUS can show real-time images without nephrotoxicity or radiation hazard and can be used as guidance for loco-regional treatment and estimation of treatment response of HCC. In addition, some data recently revealed the usefulness of CEUS in the early estimation of response to anti-cancer pharmacological (i.e., sorafenib) therapy in advanced HCC. Although CEUS has limitations in clinical practice and more investigation is needed for its validation, it is recommended as a main diagnostic modality in a few major clinical practice guidelines for HCC. Thus, greater understanding of CEUS is necessary to extend its application in real practice for diagnosis and management of diseases.
Carcinoma, Hepatocellular ; Diagnosis ; Liver ; Microbubbles ; Ultrasonography

Hepatocellular carcinoma (HCC) can be noninvasively diagnosed on the basis of its characteristic imaging findings of arterial phase enhancement and portal/delayed “washout” on computed tomography (CT) and magnetic resonance imaging (MRI) in cirrhotic patients. However, different specific diagnostic criteria have been proposed by several countries and major academic societies. In 2018, major guideline updates were proposed by the Association for the Study of Liver Diseases, European Association for the Study of the Liver (EASL), Korean Liver Cancer Association and National Cancer Center (KLCA-NCC) of Korea. In addition to dynamic CT and MRI using extracellular contrast media, these new guidelines now include magnetic resonance imaging (MRI) using hepatobiliary contrast media as the first-line diagnostic test, while the KLCA-NCC and EASL guidelines also include contrast-enhanced ultrasound (CEUS) as the second-line diagnostic test. Therefore, hepatobiliary MR contrast media and CEUS will be increasingly used for the noninvasive diagnosis and staging of HCC. In this review, we discuss the emerging role of hepatobiliary phase MRI and CEUS for the diagnosis of HCC and also review the changes in the HCC diagnostic criteria in major guidelines, including the KLCA-NCC practice guidelines version 2018. In addition, we aimed to pay particular attention to some remaining issues in the noninvasive diagnosis of HCC.
Carcinoma, Hepatocellular ; Contrast Media ; Diagnosis ; Diagnostic Tests, Routine ; Humans ; Korea ; Liver ; Liver Diseases ; Liver Neoplasms ; Magnetic Resonance Imaging ; Ultrasonography

OBJECTIVE: To determine the feasibility of microvascular flow imaging (MVFI) in comparison with color/power Doppler imaging (CDI/PDI) for detection of intratumoral vascularity in suspected post-transarterial chemoembolization (TACE) residual or recurrent hepatocellular carcinomas (HCCs) by using contrast-enhanced ultrasonography (CEUS) or hepatic angiography (HA) findings as the reference standard. MATERIALS AND METHODS: One hundred HCCs (mean size, 2.2 cm) in 100 patients treated with TACE were included in this prospective study. CDI, PDI, and MVFI were performed in tandem for evaluating intratumoral vascularity of the lesions by using an RS85 ultrasound scanner (Samsung Medison Co., Ltd.). Intratumoral vascularity in each technique was assessed by two radiologists in consensus by using a 5-point scale. Then, one of the two radiologists and another radiologist performed additional image review in the reverse order (MVFI-PDI-CDI) for evaluation of intra- and interobserver agreements. Results were then compared with those of either HA or CEUS as the reference. The McNemar test, logistic regression analysis, and intraclass correlation coefficient (ICC) were used. RESULTS: CEUS or HA revealed intratumoral vascularity in 87% (87/100) of the tumors. Sensitivity (79.3%, 69/87) and accuracy (80.0%, 80/100) of MVFI were significantly higher than those of CDI (sensitivity, 27.6% [24/87]; accuracy, 37.0% [37/100]) or PDI (sensitivity, 36.8% [32/87]; accuracy, 44.0% [44/100]) (all p < 0.05). CDI, PDI, and MVFI presented excellent intraobserver (ICCs > 0.9) and good interobserver agreements (ICCs > 0.6). CONCLUSION: MVFI demonstrated significantly higher sensitivity and accuracy than did CDI and PDI for the detection of intratumoral vascularity in suspected residual or recurrent HCCs after TACE.
Angiography ; Carcinoma, Hepatocellular ; Consensus ; Humans ; Logistic Models ; Prospective Studies ; Ultrasonography

Hepatocellular carcinoma (HCC) can be diagnosed noninvasively with contrast-enhanced dynamic computed tomography, magnetic resonance imaging, or ultrasonography on the basis of its hallmark imaging features of arterial phase hyperenhancement and washout on portal or delayed phase images. However, approximately 40% of HCCs show atypical imaging features, posing a significant diagnostic challenge for radiologists. Another challenge for radiologists in clinical practice is the presentation of many HCC mimickers such as intrahepatic cholangiocarcinoma, combined HCC-cholangiocarcinoma, arterioportal shunt, and hemangioma in the cirrhotic liver. The differentiation of HCCs from these mimickers on preoperative imaging studies is of critical importance. Hence, we will review the typical and atypical imaging features of HCCs and the imaging features of its common mimickers. In addition, we will discuss how to solve these challenges in practice.
Carcinoma, Hepatocellular ; Cholangiocarcinoma ; Hemangioma ; Liver ; Magnetic Resonance Imaging ; Ultrasonography

Contrast-enhanced ultrasound (CEUS) represents a significant breakthrough in ultrasonography (US), and it is being increasingly used for the evaluation of focal liver lesions (FLLs). CEUS is unique in that it allows non-invasive assessment of liver perfusion in real time throughout the vascular phase, which has led to dramatic improvements in the diagnostic accuracy of US in the detection and characterization of FLLs, the choice of therapeutic procedures, and the evaluation of response. Currently, CEUS is included as a part of the suggested diagnostic work-up of FLLs, including in cirrhotic patients with hepatocellular carcinoma, resulting in better patient management and cost-effective delivery of therapy.
Carcinoma, Hepatocellular ; Humans ; Liver ; Liver Cirrhosis ; Perfusion ; Ultrasonography

Eastern and Western guidelines for the management of hepatocellular carcinoma (HCC) are known to significantly differ on many points, because they reflect different diagnostic and therapeutic approaches to this cancer. Importantly, these guidelines are primarily consensus-driven when it comes to surveillance, both in term of the tests used and surveillance program design. The main difference between East and West lies in clinical practice, as several Eastern countries implement coordinated and systematic surveillance programs, while most Western countries rely on individual adherence to surveillance recommendations. This review article presents an overview of the evidence supporting surveillance programs for HCC, with a particular focus on the efficacy, cost-effectiveness, and consequences of this approach for patient survival. Western and Eastern guideline recommendations are discussed.
Carcinoma, Hepatocellular ; Fibrosis ; Humans ; Ultrasonography

PURPOSE: The purpose of this study was to examine the associations between ultrasonography (US) quality and clinical outcomes in patients undergoing surveillance for hepatocellular carcinoma. METHODS: Between 2008 and 2013, 155 patients were diagnosed with liver cancer during regular surveillance by positive US results (US group, n=82) or by computed tomography (CT) or magnetic resonance image (MRI) scanning as alternative modalities (CT/MRI group, n=73). The quality of the echogenic window, macronodularity of the liver parenchyma, and occurrence of surveillance failure (initial tumor diagnosis beyond the Milan criteria or at Barcelona Clinic Liver Cancer stage B or C) were evaluated. Overall survival was compared according to whether surveillance failure occurred. RESULTS: The patients in the CT/MRI group with negative US results had a higher proportion of parenchymal macronodularity on US than those in the US group (79.5% vs. 63.4%, P=0.028). Surveillance failure tended to be more common in the US group than in the CT/MRI group (40.2% vs. 26.0% by the BCLC staging system [P=0.061]). In the US group, surveillance failure occurred more frequently when the echogenic window was inadequate (50.0% vs. 19.4% by the Milan criteria [P=0.046]). Significantly poorer 5-year overall survival was associated with surveillance failure (P≤0.001). CONCLUSION: Parenchymal macronodularity hindered the detection of early-stage tumors during US surveillance. Using an alternative imaging modality may help prevent surveillance failure in patients with macronodular parenchyma on US. Supplemental surveillance strategies than US may also be necessary when the echogenic window is inadequate.
Carcinoma, Hepatocellular ; Diagnosis ; Humans ; Liver ; Liver Neoplasms ; Population Surveillance ; Ultrasonography