Contrast-enhanced Ultrasound Liver Imaging Reporting Research Articles

Application of the CT/MRI LI-RADS Treatment Response Algorithm to Contrast-Enhanced Ultrasound: A Feasibility Study

PurposeThe contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (TRA) is still in development. The aim of this study was to explore whether the CT/MRI LI-RADS TRA features were applicable to CEUS in evaluating the liver locoregional therapy (LRT) response.Patients and MethodsThis study was a retrospective review of a prospectively maintained database of patients with hepatocellular carcinoma undergoing ablation between July 2017 and December 2018. The standard criteria for a viable lesion were a histopathologically confirmed or typical viable appearance in the follow-up CT/MRI. Performance of the LI-RADS TRA assessing tumor viability was then compared between CEUS and CT/MRI. Inter-reader association was calculated.ResultsA total of 244 patients with 389 treated observations (118 viable) were evaluated. The sensitivity and specificity of the CEUS TRA and CT/MRI LI-RADS TRA viable categories for predicting viable lesions were 55.0% (65/118) versus 56.8% (67/118) (P = 0.480) and 99.3% (269/271) versus 96.3% (261/271) (P = 0.013), respectively. The PPV of CEUS was higher than that of CT/MRI (97.0% vs 87.0%). Subgroup analysis showed that the sensitivity was low in the 1-month assessment for both CEUS (38.1%, 16/42) and CT/MR (47.6%, 20/42) and higher in the 2–6-month assessment for both CEUS (65.7%, 23/35) and CT/MR (62.9%, 22/35). Interobserver agreements were substantial for both CEUS TRA and CT/MRI LI-RADS TRA (κ, 0.74 for both).ConclusionThe CT/MRI LI-RADS TRA features were applicable to CEUS TRA for liver locoregional therapy. The CEUS TRA for liver locoregional therapy has sufficiently high specificity and PPV to diagnose the viability of lesions after ablation.

Risk stratification for hepatocellular carcinoma of contrast-enhanced ultrasound Liver Imaging Reporting and Data System (LI-RADS) and the diagnostic performance of LR-5 and LR-M: a systematic review and meta-analysis

To evaluate the risk stratification of hepatocellular carcinoma (HCC) and overall malignancies in different contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) categories, and to explore the diagnostic performance of LR-5 for HCC and LR-M for non-HCC malignancies. The PubMed, Embase, and Cochrane Central databases were searched from 2016 to February 2021 for studies on CEUS LI-RADS v2016 and v2017. The proportion of HCC and overall malignancy in each LI-RADS category and the sensitivity, specificity, accuracy, diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUC) of LR-5 and LR-M categories were determined using a random effects model. A total of 113 studies were retrieved and 10 studies were included. A total of 5,543 patients with 6,124 lesions were included, including 4,492 HCC. There was no HCC in LR-1, and the proportion of HCC in LR-2-5 increased with the increase of category. The proportion of HCC in LR-5 was 97%, and that in LR-M was 44%. The sensitivity, specificity, and accuracy of CEUS LR-5 for HCC were 0.76, 0.95, and 0.82, respectively, and the area under the SROC curve was 0.83. The sensitivity, specificity, and accuracy of CEUS LR-M for non-HCC malignancies were 0.81, 0.92, and 0.91, and the area under the SROC curve was 0.89. The risk of HCC increases gradually from LR-1 to LR-5, in which there was no HCC lesion in LR-1 and the proportion of HCC in LR-3 was 22%, lower than that reported in earlier studies. The proportion of HCC in LR-5 was 97% and that in LR-M was 44%. LR-5 has a high specificity of 95% for the diagnosis of HCC.

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.

Diagnostic Value of CEUS LI-RADS Version 2017 in Differentiating AFP-Negative Hepatocellular Carcinoma from Other Primary Malignancies of the Liver.

Purpose: To explore the diagnostic value of Contrast-enhanced Ultrasound Liver Imaging Reporting and Data System version 2017 (CEUS LI-RADS v2017) in differentiating alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) from other primary malignancies (OM) of the liver. Methods: The data of 99 patients with primary liver malignant tumors confirmed by surgical pathology and AFP-negative from January 2018 to January 2021 were retrospectively analyzed, and the lesions were divided into 61 cases in the AFP-negative HCC group and 38 cases in the OM group according to the pathological findings, the CEUS features of the lesions were analyzed and the lesions were classified according to the CEUS LI-RADS v2017. Comparison of CEUS features between the two groups was performed using the χ2 test. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of CEUS LI-RADS v2017 for the diagnosis of AFP-negative HCC and OM were calculated using pathological findings as the gold standard. Results: The differences in features of arterial phase enhancement and wash-out between the HCC and OM groups were statistically significant (p < 0.05). The sensitivity of diagnosing HCC by LR-5 was 62.3% and the specificity was 92.1%. The sensitivity of diagnosing OM by LR-M was 92.1% and the specificity was 83.6%. Conclusions: When AFP is negative in patients with intrahepatic focal lesions, LR-5 has high specificity but low sensitivity in the diagnosis of HCC, and LR-M has high sensitivity and specificity in the diagnosis of OM. CEUS LI-RADS is a tool to differentiate AFP-negative HCC and OM effectively.

Impact of Revision of the LR-M Criteria on the Diagnostic Performance of Contrast-Enhanced Ultrasound LI-RADS

This study was aimed at revising the LI-RADS M category (LR-M) criteria to improve the diagnostic performance categories LR-5 and LR-M of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) Version 2017. We enrolled 264 patients (264 nodules) with a risk for hepatocellular carcinoma (HCC). The nodules were assigned specific CEUS LI-RADS categories. Washout onset times for all nodules were noted. The diagnostic performance of LR-5 and LR-M was analyzed based on the different early washout criterion for the LR-M category. The positive predictive values in LR-5, LR-4 and LR-3 were 98.6%, 72.2% and 16.7%, respectively, and that for non-HCC malignancies in LR-M was 25.0%. Patients in the LR-M category were reclassified using 45 s as the early washout criterion. LR-5 had higher sensitivity (65.5% vs. 76.2%, p=0.012) and area under the receiver operating characteristic curve (0.80 vs. 0.85, p=0.001) for HCC diagnosis after reclassification. LR-M also had higher specificity (71.4% vs. 81.3%, p=0.010) in diagnosing non-HCC malignancies after reclassification. Our findings suggest CEUS LR-5 is effective for HCC diagnosis. The use of 45 s as the time criterion of early washout for LR-M can improve LR-5 and LR-M performance in the diagnosis of HCC and non-HCC malignancies, respectively.

Role of Contrast-Enhanced Ultrasonography in Hepatocellular Carcinoma by Using LI-RADS and Ancillary Features: A Single Tertiary Centre Experience.

Clinical utility of ancillary features (AFs) in contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS®) is yet to be established. In this study, we assessed the diagnostic yield of CEUS LI-RADS and AFs in hepatocellular carcinoma (HCC). We retrospectively included patients with risk factors for HCC and newly diagnosed focal liver lesions (FLL). All lesions have been categorized according to the CEUS LI-RADS v2017 by an experienced sonographer blinded to clinical data and to the final diagnosis. From a total of 143 patients with 191 FLL, AFs favoring HCC were observed in 19.8% cases as hypoechoic rim and in 16.7% cases as nodule-in nodule architecture. From the total of 141 HCC cases, 83.6% were correctly classified: 57.4%- LR-5 and 26.2%- LR-4. In 9.21% cases, CEUS indicated LR-M; 2.12% cases- LR-3. The LR-5 category was 96.2% predictive (PPV) of HCC. LR-5 had 60.4% sensitivity and 93.6% specificity. PPV for primitive malignancy (LR-4 + LR-5) was 95.7%, with 88% sensitivity, 89.3% specificity and 88.4% accuracy for HCC. LR-4 category had 94.8% PPV and 26.2% sensitivity. CEUS LR4 + LR5 had 81,8% sensitivity for HCCs over 2 cm and 78.57% sensitivity for smaller HCCs. CEUS LR-5 remains an excellent diagnostic tool for HCC, despite the size of the lesion. The use of AFs might improve the overarching goal of LR-5 + LR-4 diagnosis of high specificity for HCC and exclusion of non-HCC malignancy.

The Value of Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in the Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis.

The aim of this study is to systematically evaluate the diagnostic ability of the contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) in hepatocellular carcinoma (HCC). We searched relevant studies from PubMed, Medline, and Embase database. After literature search, duplicate removal, and data extraction, we calculated and analyzed the pooled sensitivity, pooled specificity, pooled odds ratios of diagnostic, pooled likelihood ratio (LR) of positive and negative, and area under the curve (AUC), accuracy, and F1 score to evaluate the diagnostic value of CEUS LI-RADS for HCC. Thirteen studies and 6491 patients were included in this analysis. The pooled sensitivity and pooled specificity were 0.72 (95% confidence interval [CI], 0.70-0.73) and 0.92 (95% CI, 0.91-0.93), respectively. The positive LR was 8.02 (95% CI, 4.93-13.06) and the negative LR was 0.31 (95% CI, 0.27-0.37). The pooled diagnostic odds ratio was 27.91 (95% CI, 15.39-50.63). The overall AUC was 0.8406 and the accuracy was 0.77. CEUS LI-RADS is an effective and promising method to diagnose HCC.

Tumor size-based validation of contrast-enhanced ultrasound liver imaging reporting and data system (CEUS LI-RADS) 2017 for hepatocellular carcinoma characterizing

To validate the efficacy of contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) and its major features in diagnosing hepatocellular carcinoma (HCC) of different sizes in high-risk patients. Between January 2014 and December 2015, a total of 545 untreated liver nodules were included. These liver nodules were divided into two groups (<20 mm and ≥20 mm). Each nodule was classified based on CEUS LI-RADS. The diagnostic performance comparison was assessed by the chi-square test, with pathology results as the golden criterion. The accuracy, sensitivity, specificity, and positive predictive value (PPV) of CEUS LR-5 criteria in <20 mm group vs ≥20 mm group in diagnosing HCC were 60.5% vs 59.8%, 55.6% vs 57.6%, 85.7% vs 88.6 and 95.2% vs 98.5%, respectively, without significant difference (all p > 0.05). The accuracy, sensitivity and PPV of LR5/M for malignancy in <20 mm group were lower than in ≥20 mm group, with values of 79.1% vs 95.0%, 84.2% vs 95.7 and 91.4% vs 99.2%, respectively (p < 0.05). The CEUS LI-RADS has a comparable performance for diagnosing HCC between lesions ≥ 20 mm and <20 mm. For diagnosing malignancy including HCC, it has a higher efficacy for lesions ≥ 20 mm than <20 mm. 1.For diagnosing HCC, CEUS LI-RADS has comparable performances between lesions ≥ 20 mm and <20 mm.2. For diagnosing malignancy including HCC, CEUS LI-RADS has a higher efficacy for lesions ≥ 20 mm than <20 mm.

Inter-reader reliability of contrast-enhanced ultrasound Liver Imaging Reporting and Data System: a meta-analysis.

To systematically determine the inter-reader reliability of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS), with emphasis on its major features for hepatocellular carcinoma (HCC) and LR-M (LI-RADS category M) features for non-HCC malignancy. MEDLINE, EMBASE, and Cochrane databases were searched from January 2016 to March 2021 to identify original articles reporting the inter-reader reliability of CEUS LI-RADS. Meta-analytic pooled kappa values (κ) were calculated for major features [nonrim arterial-phase hyperenhancement (APHE), mild and late washout], LR-M features (rim APHE, early washout), and LI-RADS categorization using the DerSimonian-Laird random-effects model. Meta-regression analysis was performed to explore any causes of study heterogeneity. Twelve studies with a total of 2862 lesions were included. The meta-analytic pooled κ of nonrim APHE, mild and late washout, rim APHE, early washout, and LI-RADS categorization were 0.73 [95% confidence interval (CI), 0.67 - 0.79], 0.69 (95% CI, 0.54-0.84), 0.54 (95% CI, 0.37-0.71), 0.62 (95% CI, 0.45-0.79), and 0.75 (95% CI, 0.64-0.87), respectively. Compared with the major features, LR-M features had a lower meta-analytic pooled κ. Substantial study heterogeneity was noted in the LI-RADS categorization, and lesion size (p = 0.03) and the homogeneity in reader experience (p = 0.03) were significantly associated with study heterogeneity. CEUS LI-RADS showed substantial inter-reader reliability for major features and LI-RADS categorization, but relatively lower reliability was found for LR-M features. In our opinion, the definitions of imaging features require further refinement to improve the inter-reader reliability of CEUS LI-RADS.

Contrast-enhanced ultrasound Liver Imaging Reporting and Data System category M: a systematic review and meta-analysis.

PurposeA meta-analysis was conducted to determine the proportion of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System category M (LR-M) in hepatocellular carcinomas (HCCs) and non-HCC malignancies and to investigate the frequency of individual CEUS LR-M imaging features.MethodsThe MEDLINE and Embase databases were searched from January 1, 2016 to July 23, 2020 for studies reporting the proportion of CEUS LR-M in HCC and non-HCC malignancies. The meta-analytic pooled proportions of HCC and non-HCC malignancies in the CEUS LR-M category were calculated. The meta-analytic frequencies of CEUS LR-M imaging features in nonHCC malignancies were also determined. Risk of bias and applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool.ResultsTwelve studies reporting the diagnostic performance of the CEUS LR-M category were identified, as well as seven studies reporting the frequencies of individual CEUS LR-M imaging features. The pooled proportions of HCC and non-HCC malignancies in the CEUS LR-M category were 54% (95% confidence interval [CI], 44% to 65%) and 40% (95% CI, 28% to 53%), respectively. The pooled frequencies of individual CEUS LR-M imaging features in non-HCC malignancies were 30% (95% CI, 17% to 45%) for rim arterial phase hyperenhancement, 79% (95% CI, 66% to 90%) for early (<60 s) washout, and 42% (95% CI, 21% to 64%) for marked washout.ConclusionIn total, 94% of CEUS LR-M lesions were malignancies, with HCCs representing 54% and non-HCC malignancies representing 40%. The frequencies of individual CEUS LR-M imaging features varied; early washout showed the highest frequency for non-HCC malignancies.

Real-life assessment of standardized contrast-enhanced ultrasound (CEUS) and CEUS algorithms (CEUS LI-RADS\xae/ESCULAP) in hepatic nodules in cirrhotic patients\u2014a prospective multicenter study

ObjectivesHepatocellular carcinoma (HCC) can be diagnosed non-invasively with contrast-enhanced ultrasound (CEUS) in cirrhosis if the characteristic pattern of arterial phase hyperenhancement followed by hypoenhancement is present. Recent studies suggest that diagnosis based on this “hyper-hypo” pattern needs further refinement. This study compares the diagnostic accuracies of standardized CEUS for HCC according to the current guideline definition and following the newly developed CEUS algorithms (CEUS LI-RADS®, ESCULAP) in a prospective multicenter real-life setting.MethodsCirrhotic patients with liver lesions on B-mode ultrasound were recruited prospectively from 04/2018 to 04/2019, and clinical and imaging data were collected. The CEUS standard included an additional examination point after 4–6 min in case of no washout after 3 min. The diagnostic accuracies of CEUS following the guidelines (“hyper-hypo” pattern), based on the examiner’s subjective interpretation (“CEUS subjective”), and based on the CEUS algorithms ESCULAP and CEUS LI-RADS® were compared.ResultsIn total, 470 cirrhotic patients were recruited in 43 centers. The final diagnosis was HCC in 378 cases (80.4%) according to the reference standard (histology 77.4%, MRI 16.4%, CT 6.2%). The “hyper-hypo” pattern yielded 74.3% sensitivity and 63% specificity. “CEUS subjective” showed a higher diagnostic accuracy (sensitivity, 91.5%; specificity, 67.4%; positive predictive value, 92%; negative predictive value, 66%). Sensitivity was higher for ESCULAP (95%) and “CEUS subjective” (91.5%) versus CEUS LI-RADS® (65.2%; p < 0.001). Specificity was highest for CEUS LI-RADS® (78.6%; p < 0.001).ConclusionsCEUS has an excellent diagnostic accuracy for the non-invasive diagnosis of HCC in cirrhosis. CEUS algorithms may be a helpful refinement of the “hyper-hypo” pattern defined by current HCC guidelines.Key Points• Contrast-enhanced ultrasound (CEUS) has a high diagnostic accuracy for the non-invasive diagnosis of hepatocellular carcinoma (HCC) in cirrhosis.• The CEUS algorithm ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) showed the highest sensitivity, whereas the CEUS LI-RADS® (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System) algorithm yielded the highest specificity.• A standardized CEUS examination procedure with an additional examination point in the late phase, after 4–6 min in lesions with no washout after 3 min, is vital.

Diagnosis of Non-Hepatocellular Carcinoma Malignancies in Patients With Risks for Hepatocellular Carcinoma: CEUS LI-RADS Versus CT/MRI LI-RADS.

ObjectiveData regarding direct comparison of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and Computed Tomography/Magnetic Resonance Imaging (CT/MR) LI-RADS in diagnosis of non-hepatocelluar carcinoma (non-HCC) malignancies remain limited. Our study aimed to compare the diagnostic performance of the CEUS LI-RADS version 2017 and CT/MRI LI-RADS v2018 for diagnosing non-HCC malignancies in patients with risks for HCC.Materials and MethodsIn this retrospective study, 94 liver nodules pathologically-confirmed as non-HCC malignancies in 92 patients at risks for HCC from January 2009 to December 2018 were enrolled. The imaging features and the LI-RADS categories on corresponding CEUS and CT/MRI within 1 month were retrospectively analyzed according to the ACR CEUS LI-RADS v2017 and ACR CT/MRI LI-RADS v2018 by two radiologists in consensus for each algorithm. The sensitivity of LR-M category, inter-reader agreement and inter-modality agreement was compared between these two standardized algorithms.ResultsNinety-four nodules in 92 patients (mean age, 54 years ± 10 [standard deviation] with 65 men [54 years ± 11] and 27 women [54 years ± 8]), including 56 intrahepatic cholangiocarcinomas, 34 combined hepatocellular cholangiocarcinomas, two adenosquamous carcinomas of the liver, one primary hepatic neuroendocrine carcinoma and one hepatic undifferentiated sarcoma were included. On CEUS, numbers of lesions classified as LR-3, LR-4, LR-5 and LR-M were 0, 1, 10 and 83, and on CT/MRI, the corresponding numbers were 3, 0, 14 and 77. There was no significant difference in the sensitivity of LR-M between these two standardized algorithms (88.3% of CEUS vs 81.9% of CT/MRI, p = 0.210). Seventy-seven lesions (81.9%) were classified as the same LI-RADS categories by both standardized algorithms (five for LR-5 and 72 for LR-M, kappa value = 0.307). In the subgroup analysis for ICC and CHC, no significant differences were found in the sensitivity of LR-M category between these two standardized algorithms (for ICC, 94.6% of CEUS vs 89.3% of CT/MRI, p = 0.375; for CHC, 76.5% of CEUS vs 70.6% of CT/MRI, p = 0. 649).ConclusionCEUS LI-RADS v2017 and CT/MRI LI-RADS v2018 showed similar value for diagnosing non-HCC primary hepatic malignancies in patients with risks.

Combined hepatocellular-cholangiocarcinoma: can we use contrast-enhanced ultrasound Liver Imaging Reporting and Data System (LI-RADS) to predict the patient’s survival?

To evaluate the relationship between contrast-enhanced (CE) ultrasound Liver Reporting and Data System (LI-RADS) classification of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and their histopathological component predominance, and to determine if the CEUS LI-RADS category can be used to predict the patient's survival after surgical resection. Between January 2011 and December 2018, medical records and CEUS of patients with pathologically proven cHCC-CCA were studied. The predominance of hepatocellular carcinoma (HCC)/intrahepatic cholangiocarcinoma (ICC) component of cHCC-CCA was analyzed by histopathology. The proportion of HCC-predominant cHCC-CCA in different LI-RADS category was compared by using Fisher's exact test. Factors affecting tumor recurrence were analyzed by Cox proportional hazard model. Disease-free survival (DFS) was estimated by using Kaplan-Meier survival curve and compared by log-rank test. The study included 37 cHCC-CCA patients (33 men, 4 women; average age, 50.4 ± 11.0 years) and 37 nodules (mean diameter, 6.1 ± 3.9 cm). According to CEUS LI-RADS, 62.2% (23/37), 18.9% (7/37), and 18.9% (7/37) of cHCC-CCA were classified as LR-M, LR-5, and LR-TIV, respectively. The ratio of HCC predominance in LR-5 was 100% (10/10) vs 81.5% (22/27) in the LR-M group (p = 0.591). In our population, LR-5 patients had longer DFS than LR-M and LR-TIV patients combined (median DFS: 18.0 vs 6.4 months, p = 0.016). Multiple lesions (hazard ratio, 3.1; p = 0.007), tumor size (≥ 5 cm, hazard ratio, 4.1; p = 0.003), and CEUS LI-RADS category (LR-M and LR-TIV, hazard ratio, 4.7; p = 0.011) showed independent association with shorter DFS. cHCC-CCA characterized as LR-5 on CEUS tend to represent HCC-predominant tumors with significantly longer disease-free survival compared to cHCC-CCA categorized as LR-M and LR-TIV. • By using the American College of Radiology contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS), majority (30/37, 81.1%) of cHCC-CCA tumors were classified as LR-M or LR-TIV and only 18.9% (7/30) of cHCC-CCA were categorized as LR-5. • Patients with CEUS LR-5 cHCC-CCA had statistically significant longer disease-free time than those with LR-M and TIV cHCC-CCA (median DFS: 18.0 vs 6.4 months, p = 0.016). • Multiple lesions (hazard ratio, 3.1; p = 0.007), tumor size (≥ 5 cm, hazard ratio, 4.1; p = 0.003), and CEUS LI-RADS category (LR-M and LR-TIV, hazard ratio, 4.7; p = 0.011) showed independent association with shorter DFS.

Contrast-enhanced ultrasound in association with serum biomarkers for differentiating combined hepatocellular-cholangiocarcinoma from hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

BACKGROUNDCombined hepatocellular-cholangiocarcinoma (CHC) is a rare type of primary liver cancer. Due to its complex histopathological characteristics, the imaging features of CHC can overlap with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).AIMTo investigate the possibility and efficacy of differentiating CHC from HCC and ICC by using contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and tumor biomarkers.METHODSBetween January 2016 and December 2019, patients with histologically confirmed CHC, ICC and HCC with chronic liver disease were enrolled. The diagnostic formula for CHC was as follows: (1) LR-5 or LR-M with elevated alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9); (2) LR-M with elevated AFP and normal CA19-9; or (3) LR-5 with elevated CA19-9 and normal AFP. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve were calculated to determine the diagnostic value of the criteria.RESULTSAfter propensity score matching, 134 patients (mean age of 51.4 ± 9.4 years, 108 men) were enrolled, including 35 CHC, 29 ICC and 70 HCC patients. Based on CEUS LI-RADS classification, 74.3% (26/35) and 25.7% (9/35) of CHC lesions were assessed as LR-M and LR-5, respectively. The rates of elevated AFP and CA19-9 in CHC patients were 51.4% and 11.4%, respectively, and simultaneous elevations of AFP and CA19-9 were found in 8.6% (3/35) of CHC patients. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under the receiver operating characteristic curve of the aforementioned diagnostic criteria for discriminating CHC from HCC and ICC were 40.0%, 89.9%, 58.3%, 80.9%, 76.9% and 0.649, respectively. When considering the reported prevalence of CHC (0.4%-14.2%), the positive predictive value and NPV were revised to 1.6%-39.6% and 90.1%-99.7%, respectively.CONCLUSIONCHCs are more likely to be classified as LR-M than LR-5 by CEUS LI-RADS. The combination of the CEUS LI-RADS classification with serum tumor markers shows high specificity but low sensitivity for the diagnosis of CHC. Moreover, CHC could be confidently excluded with high NPV.

Diagnostic Accuracy of Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) for Differentiating Between Hepatocellular Carcinoma and Other Hepatic Malignancies in High-Risk Patients: A Meta-Analysis.

The American College of Radiology (ACR) contrast-enhanced ultrasound liver imaging reporting and data system (CEUS LI-RADS), which includes diagnostic criteria for hepatocellular carcinoma (HCC) and other hepatic malignancies (OM), is increasingly used in clinical practice. This study performed a meta-analysis to assess the diagnostic accuracy of CEUS LI-RADS for differentiating between HCC and OM in high-risk patients. PubMed, Embase (Ovid), and Cochrane (CENTRAL) were searched for relevant studies. All studies that reported the percentage of HCC and OM in the LI-RADS categories were included. Random-effects models were used to calculate the pooled sensitivity and specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve. Eight studies involving 4215 focal liver lesions were included in the final analysis. The pooled sensitivity and specificity of the LR-5 criteria for HCC were 0.71 (95 % CI, 0.69-0.72) and 0.88 (0.85-0.91), respectively, the DOR was 18.36 (7.41-45.52), and the area under the SROC curve (AUC) was 0.8128. The pooled sensitivity and specificity of the LR-M criteria for OMs were 0.85 (0.81-0.88) and 0.86 (0.85-0.87), the DOR was 27.82 (11.83-65.40), respectively, and the SROC AUC was 0.9098. The CEUS LI-RADS can effectively distinguish HCC from other hepatic malignancy in high-risk patients based on LR-5 criteria and LR-M criteria. However, further studies are needed for validation due to the limited number of included studies and the potential heterogeneity among the included studies.

Diagnostic efficacy of contrast-enhanced ultrasound versus MRI Liver Imaging Reporting and Data System (LI-RADS) for categorising hepatic observations in patients at risk of hepatocellular carcinoma

To investigate the diagnostic efficacy of the contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) for categorising hepatic observations in patients at risk of hepatocellular carcinoma (HCC) compared with magnetic resonance imaging (MRI) LI-RADS. CEUS and MRI data were analysed retrospectively according to the LI-RADS scheme. Follow-up results and pathological findings served as the reference standard. Receiver operating characteristic (ROC) curve analysis was used to reveal the area under the curve (AUC). The sensitivity, specificity, accuracy, and positive (PPV) and negative predictive values (NPV) of LR-5 for determining HCC were calculated. The intra-observer agreement of CEUS LI-RADS was also evaluated. Eighty-four patients with 86 liver observations were enrolled. Forty-two observations were classified as LR-5 by CEUS and MRI, respectively. Based on the reference standard, 53 nodules were HCC. The AUCs were 0.876 for CEUS and 0.873 for MRI, without a significant difference (Z=0.050, p=0.960). The sensitivity, specificity, PPV, NPV, and accuracy of LR-5 was 75.47%, 93.94%, 95.24%, 70.45%, 82.56% with CEUS and 73.58%, 90.9%, 92.86%, 68.18%, 80.23% with MRI, respectively. There was a significant difference in specificity between CEUS and MRI (p=0.006). There was almost perfect agreement for arterial phase hyperenhancement (k=0.870), substantial agreement for washout (k=0.765) and CEUS LI-RADS category (k=0.787). The CEUS LI-RADS scheme is an effective diagnostic tool for HCC with substantial intra-observer reliability. The diagnostic performance of CEUS LI-RADS for determining HCC was comparable to MRI LI-RADS, and the specificity of CEUS LR-5 was significantly higher.

Accuracy of contrast-enhanced ultrasound liver imaging reporting and data system: a systematic review and meta-analysis.

After the introduction of the contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS), several studies have reported on its performance, but the reported data vary considerably. Therefore, we performed a systematic review and meta-analysis to determine the diagnostic performance of CEUS LI-RADS in patients at risk for hepatocellular carcinoma (HCC) and investigate the causes of study heterogeneity. Original studies published until May 30, 2020, investigating the diagnostic performance of CEUS LI-RADS were identified in the MEDLINE, EMBASE, and Cochrane library databases. Study quality was assessed using the QUADAS-2 tool. Meta-analytic summary sensitivity and specificity for the diagnosis of HCC were calculated using a bivariate random-effects model. Meta-regression analysis was performed to explore the causes of study heterogeneity. Of the 105 articles screened, eight studies were finally analyzed (5428 hepatic observations). The summary sensitivity and specificity of CEUS LI-RADS category 5 (LR-5) for diagnosing HCC were 73% [95% confidence interval (CI) 65-79%; I2 = 93%] and 95% (95% CI 91-97%; I2 = 89%), respectively. Substantial study heterogeneity was noted in both sensitivity and specificity. Study heterogeneity was significantly associated with the proportion of cases of HCC and the type of reference standard (p ≤ 0.05). CEUS LI-RADS had high pooled specificity for diagnosing HCC but suboptimal pooled sensitivity. Substantial study heterogeneity was found, which was significantly associated with the proportion of cases of HCC and the type of reference standard.

Usefulness of Modified CEUS LI-RADS for the Diagnosis of Hepatocellular Carcinoma Using Sonazoid.

The Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) was introduced for classifying suspected hepatocellular carcinoma (HCC). However, it cannot be applied to Sonazoid. We assessed the diagnostic usefulness of a modified CEUS LI-RADS for HCC and non-HCC malignancies based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Patients with chronic liver disease at risk for HCC were evaluated retrospectively. Nodules ≥1 cm with arterial phase hyperenhancement, no early washout (within 60 s), and contrast defects in the Kupffer phase were classified as LR-5. Nodules showing early washout, contrast defects in the Kupffer phase, and/or rim enhancement were classified as LR-M. A total of 104 nodules in 104 patients (median age: 70.0 years; interquartile range: 54.5–78.0 years; 74 men) were evaluated. The 48 (46.2%) LR-5 lesions included 45 HCCs, 2 high-flow hemangiomas, and 1 adrenal rest tumor. The PPV of LR-5 for HCC was 93.8% (95% confidence interval (CI): 82.8–98.7%). The 22 (21.2%) LR-M lesions included 16 non-HCC malignancies and 6 HCCs. The PPV of LR-M for non-HCC malignancies, including six intrahepatic cholangiocarcinomas, was 100% (95% CI: 69.8–100%). In conclusion, in the modified CEUS LI-RADS for Sonazoid, LR-5 and LR-M are good predictors of HCC and non-HCC malignancies, respectively.

Contrast-enhanced ultrasound LI-RADS 2017: comparison with CT/MRI LI-RADS.

To compare the classification based on contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) with that of contrast-enhanced CT and MRI (CECT/MRI) LI-RADS for liver nodules in patients at high risk of hepatocellular carcinoma. Two hundred thirty-nine patients with 273 nodules were enrolled in this retrospective study. Each nodule was categorized according to the CEUS LI-RADS version 2017 and CECT/MRI LI-RADS version 2017. The diagnostic performance of CEUS and CECT/MRI was compared. The reference standard was histopathology diagnosis. Inter-modality agreement was assessed with Cohen's kappa. The inter-modality agreement for CEUS LI-RADS and CECT/MRI LI-RADS was fair with a kappa value of 0.319 (p < 0.001). The positive predictive values (PPVs) of hepatocellular carcinoma (HCC) in LR-5, LR-4, and LR-3 were 98.3%, 60.0%, and 25.0% in CEUS, and 95.9%, 65.7%, and 48.1% in CECT/MRI, respectively. The sensitivities and specificities of LR-5 for diagnosing HCC were 75.6% and 93.8% in CEUS, and 83.6% and 83.3% in CECT/MRI, respectively. The positive predictive values of non-HCC malignancy in CEUS LR-M and CECT/MRI LR-M were 33.9% and 93.3%, respectively. The sensitivity, specificity, and accuracy for diagnosing non-HCC malignancy were 90.9%, 84.5%, and 85.0% in CEUS LR-M and 63.6%, 99.6%, and 96.7% in CECT/MRI LR-M, respectively. The inter-modality agreement of the LI-RADS category between CEUS and CECT/MRI is fair. The positive predictive values of HCCs in LR-5 of the CEUS and CECT/MRI LI-RADS are comparable. CECT/MRI LR-M has better diagnostic performance for non-HCC malignancy than CEUS LR-M. • The inter-modality agreement for the final LI-RADS category between CEUS and CECT/MRI is fair. • The LR-5 of CEUS and CECT/MRI LI-RADS corresponds to comparable positive predictive values (PPVs) of HCC. For LR-3 and LR-4 nodules categorized by CECT/MRI, CEUS examination should be performed, at least if they can be detected on plain ultrasound. • CECT/MRI LR-M has better diagnostic performance for non-HCC malignancy than CEUS LR-M. For LR-M nodules categorized by CEUS, re-evaluation by CECT/MRI is necessary.

Contrast-enhanced ultrasound liver imaging reporting and data system for diagnosing hepatocellular carcinoma: A meta-analysis.

Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing CEUS at high risk for hepatocellular carcinoma (HCC). We performed a meta-analysis to determine the diagnostic performance of the CEUS LR-5 for HCC and the pooled proportions of HCCs in each CEUS LI-RADS category. We searched multiple databases for studies reporting the diagnostic accuracy of the CEUS LI-RADS. Random-effects model was used to determine summary estimates of the diagnostic performance of CEUS LR-5 and the pooled proportions of HCCs in each CEUS LI-RADS category. Risk of bias and concerns regarding applicability were evaluated with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Eleven studies were included in the final analysis, which consisted of 5535 observations with 3983 HCCs. The pooled per-observation sensitivity and specificity of the CEUS LR-5 for diagnosing HCC were 69% (95% confidence interval [CI], 64%-73%) and 92% (95% CI, 83%-96%) respectively. The pooled proportions of HCCs were 0% (95% CI, 0-0%) for LR-1, 1% (95% CI, 0%-4%) for CEUS LR-2, 26% (95% CI, 14%-39%) for CEUS LR-3, 77% (95% CI, 68%-86%) for CEUS LR-4, 97% (95% CI, 95%-98%) for CEUS LR-5, 57% (95% CI, 44%-69%) for CEUS LR-M and 100% (95% CI, 93%-100%) for CEUS LR-5V or TIV. The CEUS LR-5 category showed moderate sensitivity and high specificity for diagnosing HCC. The proportion of HCCs was higher in the higher CEUS LI-RADS categories.