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

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

Contrast-enhanced ultrasound (CEUS) is a powerful technique for differentiating focal liver lesions (FLLs) without the risks of potential nephrotoxicity or ionizing radiation. In the diagnostic algorithm for FLLs on CEUS, washout is an important feature, as its presence is highly suggestive of malignancy and its characteristics are useful in distinguishing hepatocellular from non-hepatocellular malignancies. Interpreting washout on CEUS requires an understanding that microbubble contrast agents are strictly intravascular, unlike computed tomography or magnetic resonance imaging contrast agents. This review explains the definition and types of washout on CEUS in accordance with the 2017 version of the CEUS Liver Imaging Reporting and Data System and presents their applications to differential diagnosis with illustrative examples. Additionally, we propose potential mechanisms of rapid washout and describe the washout phenomenon in benign entities.
Carcinoma, Hepatocellular ; Contrast Media ; Diagnosis ; Diagnosis, Differential ; Information Systems ; Liver ; Magnetic Resonance Imaging ; Microbubbles ; Neoplasm Metastasis ; Radiation, Ionizing ; Ultrasonography

Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death worldwide. Prognosis and treatment options largely depend on tumor stage at diagnosis, with curative treatments only available if detected at an early stage. However, two thirds of patients with HCC are diagnosed at a late stage and not eligible for cure. Therefore several liver professional societies recommend HCC surveillance using abdominal ultrasound with or without alpha fetoprotein in at-risk populations, including patients with cirrhosis and subsets of those with chronic hepatitis B. Available data suggest HCC surveillance can significantly improve early tumor detection, curative treatment eligibility, and overall survival. However, the potential benefits of HCC surveillance must be considered in light a shifting HCC demographic from a viral-mediated cancer to an increasing proportion of patients having non-alcoholic steatohepatitis, which has been shown to limit ultrasound sensitivity and may mitigate observed benefits. Further, benefits of HCC surveillance must be weighed against potential physical, financial and psychological harms. Continued data for both benefits and harms of HCC surveillance in contemporary populations are necessary. In the interim, providers should continue to strive for high quality HCC surveillance in at-risk patients.
alpha-Fetoproteins ; Carcinoma, Hepatocellular ; Diagnosis ; Fatty Liver ; Fibrosis ; Hepatitis B, Chronic ; Humans ; Liver ; Liver Neoplasms ; Mass Screening ; Prognosis ; Ultrasonography

The goal of this review is to present the similarities and differences among the latest guidelines for noninvasive diagnosis of hepatocellular carcinoma (HCC) of American Association for the Study of Liver Disease (AASLD), European Association for the Study of the Liver (EASL), Liver Imaging Reporting and Data System (LI-RADS), Asian Pacific Association for the Study of the Liver (APASL), and Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) of Korea. In 2018, major guideline updates have been proposed by the AASLD, EASL and KLCA-NCC; AASLD newly incorporated LI-RADS into their HCC diagnostic algorithm. The AASLD and EASL guidelines now include magnetic resonance imaging (MRI) using hepatobiliary contrast media as a first-line diagnostic test in addition to dynamic computed tomography and MRI using extracellular contrast media and the KLCA-NCC and EASL guidelines also include contrast-enhanced ultrasound as a second-line diagnostic test. We will comprehensively review the HCC surveillance and diagnostic algorithms and compare and highlight key features for each guideline. We also address limitations of current systems for the noninvasive diagnosis of HCC.
Asian Continental Ancestry Group ; Carcinoma, Hepatocellular ; Contrast Media ; Diagnosis ; Diagnostic Tests, Routine ; Humans ; Information Systems ; Korea ; Liver ; Liver Diseases ; Liver Neoplasms ; Magnetic Resonance Imaging ; 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