Diagnostic Criteria For Hepatocellular Carcinoma Research Articles

Contrast-Enhanced Ultrasound With Perfluorobutane for Hepatocellular Carcinoma Diagnosis: Comparison of Imaging Phases and Diagnostic Criteria.

BACKGROUND. Contrast-enhanced ultrasound (CEUS) with perfluorobutane has used varying protocols and diagnostic criteria for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of this article was to assess diagnostic performance for HCC of CEUS with perfluorobutane in high-risk patients using various criteria. METHODS. This retrospective post hoc study evaluating individual patient data from three earlier prospective studies from one hospital included 204 patients (136 men, 68 women; mean age, 63 ± 11 [SD] years) at high risk of HCC with 213 liver observations. Patients underwent CEUS using perfluorobutane from March 2019 to June 2022. Three radiologists (the examination's operator and two subsequent reviewers) independently interpreted examinations, assessing arterial, portal venous (arterial phase completion through 2 minutes), transitional (2-5 minutes after injection), and Kupffer (≥ 10 minutes after injection) phase findings. Six criteria for HCC were tested: 1, any arterial phase hyperenhancement (APHE) with Kupffer phase hypoenhancement; 2, nonrim APHE with Kupffer phase hypoenhancement; 3, nonrim APHE with portal venous washout; 4, nonrim APHE with portal venous washout and/or Kupffer phase hypoenhancement; 5, nonrim APHE with portal venous and/or transitional washout; 6, nonrim APHE with any of portal venous washout, transitional washout, or Kupffer phase hypoenhancement. Depending on the criteria, observations were instead deemed to be a non-HCC malignancy if showing rim APHE, early washout (at < 1 minute), or marked washout (at 2 minutes). Reference was pathology for malignant observations and pathology or imaging follow-up for benign observations. Diagnostic performance was assessed, pooling readers' data. RESULTS. Criterion 1 (no recognized features of non-HCC malignancy) had highest sensitivity (86.9%) but lowest specificity (43.2%) for HCC. Compared with nonrim APHE and portal venous washout (criterion 3), the addition of Kupffer phase hypoenhancement (criterion 4), transitional washout (criterion 5), or either feature (criterion 6) significantly increased sensitivity (34.4% vs 62.6-64.2%) and accuracy (61.8% vs 75.1-76.5%), but significantly decreased specificity (98.5% vs 91.9-94.1%). Criteria 2, 4, 5, and 6 (all incorporating transitional washout and/or Kupffer phase hypoenhancement) showed no significant differences in sensitivity (62.6-64.2%), specificity (91.9-94.1%), or accuracy (75.1-76.5%). CONCLUSION. Recognition of features of non-HCC malignancy improved specificity for HCC. Incorporation of the findings of transitional washout and/or Kupffer phase hypoenhancement improved sensitivity and accuracy, albeit lowered specificity, versus arterial and portal venous findings alone, without further performance variation among criteria incorporating those two findings. CLINICAL IMPACT. Kupffer phase acquisition may be optional for observations classified as HCC or non-HCC malignancy by arterial, portal venous, and transitional phases.

Diagnosing Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasonography: 2023 Guidelines from the Korean Society of Radiology and the Korean Society of Abdominal Radiology

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.

Sonazoid-enhanced ultrasonography for noninvasive imaging diagnosis of hepatocellular carcinoma: special emphasis on the 2022 KLCA-NCC guideline.

Contrast-enhanced ultrasonography (CEUS) is a noninvasive imaging modality used to diagnose hepatocellular carcinoma (HCC) based on specific imaging features, without the need for pathologic confirmation. Two types of ultrasound contrast agents are commercially available: pure intravascular agents (such as SonoVue) and Kupffer agents (such as Sonazoid). Major guidelines recognize CEUS as a reliable imaging method for HCC diagnosis, although they differ depending on the contrast agents used. The Korean Liver Cancer Association-National Cancer Center guideline includes CEUS with either SonoVue or Sonazoid as a second-line diagnostic technique. However, Sonazoid-enhanced ultrasound is associated with several unresolved issues. This review provides a comparative overview of these contrast agents regarding pharmacokinetic features, examination protocols, diagnostic criteria for HCC, and potential applications in the HCC diagnostic algorithm.

Hepatocellular carcinoma: State of the art diagnostic imaging.

Primary liver cancer is the fourth most common malignancy worldwide, with hepatocellular carcinoma (HCC) comprising up to 90% of cases. Imaging is a staple for surveillance and diagnostic criteria for HCC in current guidelines. Because early diagnosis can impact treatment approaches, utilizing new imaging methods and protocols to aid in differentiation and tumor grading provides a unique opportunity to drastically impact patient prognosis. Within this review manuscript, we provide an overview of imaging modalities used to screen and evaluate HCC. We also briefly discuss emerging uses of new imaging techniques that offer the potential for improving current paradigms for HCC characterization, management, and treatment monitoring.

Diagnosing Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasonography: 2023 Guidelines From the Korean Society of Radiology and the Korean Society of Abdominal Radiology.

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.

Identification of the origin of tumor in vein: comparison between CEUS LI-RADS v2017 and v2016 for patients at high risk

ObjectivesTo compare the diagnostic performance of the Contrast-Enhanced Ultrasound (CEUS) Liver Imaging Report and Data System (LI-RADS) v2016 and v2017 in identifying the origin of tumor in vein (TIV).MethodsFrom April 2014 to December 2018, focal liver lesions (FLLs) accompanied by TIV formation in patients at high risk for hepatocellular carcinoma (HCC) were enrolled. Histologic evaluation or composite imaging reference standard were served as the reference standard. Each case was categorized according to the CEUS LI-RADS v2016 and v2017, respectively. Diagnostic performance of CEUS LI-RADS v2016 and v2017 in identifying the originated tumor of TIV was validated via sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value.ResultsA total of 273 FLLs with TIV were analyzed finally, including 266 HCCs and 7 non-HCCs. In v2016, when adopting all TIV as LR-5V, the accuracy and PPV in identifying the originated tumor were both 97.4%. In v2017, when assigning TIV according to contiguous FLLs CEUS LI-RADS category, the accuracy and PPV were 61.9% and 99.4% in subclass of LR-5 as the diagnostic criteria of HCC, and 64.1% and 99.4% in subclass of LR-4/5 as the criteria of HCC diagnosis. There were significant differences in diagnostic accuracy between CEUS LI-RADS v2016 and v2017 in identifying the originated tumor of TIV (p < 0.001).ConclusionsCEUS LI-RADS v2016 could be better than v2017 in identifying the originated tumor of TIV.

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.

The Principle of Contrast-enhanced Ultrasound and the Diagnosis of Hepatocellular Carcinoma

Contrast-enhanced ultrasound (CEUS) is a specialized ultrasound performed with microbubble contrast agents. It is valuable for characterizing hepatic lesions without renal toxicity or radiation hazard. This review provides up-to-date practical knowledge of CEUS to make the interpretation of CEUS more accurate and clinically relevant. It includes the principle of CEUS, comparison of two kinds of contrast agents (the pure blood-pool agent and the Kupffer agent), diagnostic criteria for hepatocellular carcinoma, and its role in the diagnostic algorithms.

Perfluorobutane-enhanced ultrasonography with a Kupffer phase: improved diagnostic sensitivity for hepatocellular carcinoma.

To evaluate the diagnostic accuracy of perfluorobutane contrast-enhanced ultrasonography (CEUS) for hepatocellular carcinoma (HCC) and to explore how accuracy can be improved compared to conventional diagnostic criteria in at-risk patients. A total of 123 hepatic nodules (≥ 1 cm) from 123 at-risk patients who underwent perfluorobutane CEUS between 2013 and 2020 at three institutions were retrospectively analyzed. Ninety-three percent of subjects had pathological results, except benign lesions stable in follow-up images. We evaluated presence of arterial phase hyperenhancement (APHE), washout time and degree, and Kupffer phase (KP) defects. KP defects are defined as hypoenhancing lesions relative to the liver in KP. HCC was diagnosed in two ways: (1) Liver Imaging Reporting and Data System (LI-RADS) criteria defined as APHE and late (≥ 60 s)/mild washout, and (2) APHE and Kupffer (AK) criteria defined as APHE and KP defect. We explored grayscale features that cause misdiagnosis of HCC and reflected in the adjustment. Diagnostic performance was compared using McNemar's test. There were 77 HCCs, 15 non-HCC malignancies, and 31 benign lesions. An ill-defined margin without hypoechoic halo on grayscale applied as a finding that did not suggest HCC. Regarding diagnosis of HCC, sensitivity of AK criteria (83.1%; 95% confidence interval [CI]: 72.9-90.7%) was higher than that of LI-RADS criteria (75.3%; 95% CI: 64.2-84.4%; p = 0.041). Specificity was 91.3% (95% CI: 79.2-97.6%) in both groups. On perfluorobutane CEUS, diagnostic criteria for HCC using KP defect with adjustment by grayscale findings had higher diagnostic performance than conventional criteria without losing specificity. • Applying Kupffer phase defect instead of late/mild washout and adjusting with grayscale findings can improve the diagnostic performance of perfluorobutane-enhanced US for HCC. • Adjustment with ill-defined margins without a hypoechoic halo for features unlikely to be HCC decreases false positives for HCC diagnosis using the perfluorobutane-enhanced US. • After adjustment with grayscale findings, the sensitivity and accuracy of the APHE and Kupffer criteria were higher than those of the LI-RADS criteria; specificity was 91.3% for both.

Abstract 5926: Hepatocellular carcinoma in the hepatitis B vaccinated and nonvaccinated age groups in The Gambia

Abstract INTRODUCTION: Hepatitis B vaccination was started in The Gambia in July 1986 and nationwide coverage was achieved in February1990. However not much is known about its effect in the prevention of Hepatocellular carcinoma (HCC) in The Gambia. OBJECTIVE: We assess the differences in the features of HCC in both the Hepatitis B vaccinated and non-vaccinated age groups in The Gambia. METHOD: Patients with suspected HCC who were referred to the main liver clinic at the Medical Research Council, Gambia Unit (MRCG) were recruited from June 2011 to September 2019. The diagnostic criteria for HCC comprised of ultrasound demonstration of liver mass ≥2 cm with or without clinical features combined with alpha-fetoprotein (AFP) level of ≥200 ng/ml and/or histopathological confirmation. Clinical, radiological, fibroelastrography and laboratory data were collected in all patients. RESULTS: Five hundred and forty two patients were recruited into the study. The majority (91.3%) of the patients were in the non-vaccinated age group and most (88.8%) were born in The Gambia. Those born outside The Gambia were mostly Senegalese, Sierreleonean, and Guineans. The patients in the vaccinated age group were much younger and less likely to be born in The Gambia. They were also more likely to have higher AFP levels, positive HBsAg and a lower creatinine level as compared to those patients in the non-vaccinated age group. There was no difference in clinical manifestations, Liver Function tests and median survival. CONCLUSIONS: The early introduction of Nationwide Hepatitis B vaccination in 1990 into the EPI program in The Gambia may have had a positive effect in the incidence of Hepatocellular Carcinoma in the vaccinated age group. Compared to neighbouring countries, The Gambia seems to be leading the path for Hepatitis B elimination.To strengthen these gains, a nationwide screening and treatment program needs to be implemented for those in the non-vaccinated age groups. Citation Format: Sheikh Omar Bittaye, Ramou Njie. Hepatocellular carcinoma in the hepatitis B vaccinated and nonvaccinated age groups in The Gambia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5926.

Impact of the Liver Imaging Reporting and Data System on Research Studies of Diagnosing Hepatocellular Carcinoma Using MRI

ObjectiveSince its introduction in 2011, the CT/MRI diagnostic Liver Imaging Reporting and Data System (LI-RADS) has been updated in 2014, 2017, and 2018. We evaluated the impact of CT/MRI diagnostic LI-RADS on liver MRI research methodology for the diagnosis of hepatocellular carcinoma (HCC).Materials and MethodsThe MEDLINE, EMBASE, and Cochrane databases were searched for original articles reporting the diagnostic performance of liver MRI for HCC between 2011 and 2019. The MRI techniques, image analysis methods, and diagnostic criteria for HCC used in each study were investigated. The studies were classified into three groups according to the year of publication (2011–2013, 2014–2016, and 2017–2019). We compared the percentage of studies adopting MRI techniques recommended by LI-RADS, image analysis methods in accordance with the lexicon defined in LI-RADS, and diagnostic criteria endorsed by LI-RADS. We compared the pooled sensitivity and specificity between studies that used the LI-RADS and those that did not.ResultsThis systematic review included 179 studies. The percentages of studies using imaging techniques recommended by LI-RADS were 77.8% for 2011–2013, 85.7% for 2014–2016, and 84.2% for 2017–2019, with no significant difference (p = 0.951). After the introduction of LI-RADS, the percentages of studies following the LI-RADS lexicon were 0.0%, 18.4%, and 56.6% in the respective periods (p < 0.001), while the percentages of studies using the LI-RADS diagnostic imaging criteria were 0.0%, 22.9%, and 60.7%, respectively (p < 0.001). Studies that did not use the LI-RADS and those that used the LI-RADS version 2018 showed no significant difference in sensitivity and specificity (86.3% vs. 77.7%, p = 0.102 and 91.4% vs. 89.9%, p = 0.770, respectively), with some difference in heterogeneity (I2 = 94.3% vs. 86.7% in sensitivity and I2 = 86.6% vs. 53.2% in specificity).ConclusionLI-RADS imparted significant changes in the image analysis methods and diagnostic criteria used in liver MRI research for the diagnosis of HCC.

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.

Subcentimeter hepatocellular carcinoma in treatment-naïve patients: noninvasive diagnostic criteria and tumor staging on gadoxetic acid-enhanced MRI.

It is controversial to adopt non-invasive diagnostic criteria of hepatocellular carcinoma (HCC) in subcentimeter lesions. This study was aimed to define the optimal noninvasive diagnostic criteria of subcentimeter HCC and to evaluate the effect on tumor staging. We included 110 treatment-naïve patients at risk of HCC and eligible for curative treatment who had subcentimeter lesions (n = 136) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) performed between January 2013 and December 2013. Modified diagnostic criteria for subcentimeter HCC were developed using logistic regression analysis. Accuracies of MR staging with and without using the modified criteria were compared by generalized estimating equation test using pathologic staging as reference standards. Subgroup analysis was performed for patients with co-existing HCC ≥ 1 cm (co-HCC). The modified criteria (presence of co-HCC, arterial phase hyperenhancement, and hypointensity on transitional phase [TP]) showed 61.5% (95% CI, 41.6-78.2) of sensitivity and 98.2% (95% CI, 93.0-99.5) of specificity. Including subcentimeter HCCs improved the accuracy of MR staging from 84.5 to 94.5% (p = 0.001). Fifty percent of subcentimeter lesions found in patients with co-HCCs were HCC, whereas 5.9% of them without co-HCCs were HCC (p = 0.001). In the subgroup with co-HCCs, the accuracy of MR staging with subcentimeter HCCs was improved from 69.0% to 92.8% (p = 0.001). Including subcentimeter HCCs based on the modified diagnostic criteria (co-existing HCC ≥ 1 cm, arterial phase hyperenhancement, and hypointensity on TP) improved MR staging accuracy. • Fifty percent of non-benign appearing subcentimeter lesions found in patients with co-HCCs were HCC, whereas 5.9% of them without co-HCCs were HCC (p = 0.001). • Including subcentimeter HCCs improved the accuracy of MR staging from 84.5 to 94.5% (p = 0.001).

The threshold of alpha-fetoprotein (AFP) for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

ObjectiveHepatocellular carcinoma (HCC) has become a pressing health problem facing the world today due to its high morbidity, high mortality, and late discovery. As a diagnostic criteria of HCC, the exact threshold of Alpha-fetoprotein (AFP) is controversial. Therefore, this study was aimed to systematically estimate the performance of AFP in diagnosing HCC and to clarify its optimal threshold.MethodsMedline and Embase databases were searched for articles indexed up to November 2019. English language studies were included if both the sensitivity and specificity of AFP in the diagnosis of HCC were provided. The basic information and accuracy data included in the studies were extracted. Combined estimates for sensitivity and specificity were statistically analyzed by random-effects model using MetaDisc 1.4 and Stata 15.0 software at the prespecified threshold of 400 ng/mL, 200 ng/mL, and the range of 20–100 ng/mL. The optimal threshold was evaluated by the area under curve (AUC) of the summary receiver operating characteristic (SROC).ResultsWe retrieved 29,828 articles and included 59 studies and 1 review with a total of 11,731 HCC cases confirmed by histomorphology and 21,972 control cases without HCC. The included studies showed an overall judgment of at risk of bias. Four studies with AFP threshold of 400 ng/mL showed the summary sensitivity and specificity of 0.32 (95%CI 0.31–0.34) and 0.99 (95%CI 0.98–0.99), respectively. Four studies with AFP threshold of 200 ng/mL showed the summary sensitivity and specificity of 0.49 (95%CI 0.47–0.50) and 0.98 (95%CI 0.97–0.99), respectively. Forty-six studies with AFP threshold of 20–100 ng/mL showed the summary sensitivity and specificity of 0.61 (95%CI 0.60–0.62) and 0.86 (95%CI 0.86–0.87), respectively. The AUC of SROC and Q index of 400 ng/mL threshold were 0.9368 and 0.8734, respectively, which were significantly higher than those in 200 ng/mL threshold (0.9311 and 0.8664, respectively) and higher than those in 20–100 ng/mL threshold (0.8330 and 0.7654, respectively). Furthermore, similar result that favored 400 ng/mL were shown in the threshold in terms of AFP combined with ultrasound.ConclusionAFP levels in serum showed good accuracy in HCC diagnosis, and the threshold of AFP with 400 ng/mL was better than that of 200 ng/mL in terms of sensitivity and specificity no matter AFP is used alone or combined with ultrasound.

Cirrhotic Nodule Transformation to Hepatocellular Carcinoma: Natural History and Predictive Biomarkers on Contrast-Enhanced Ultrasound.

OBJECTIVE. The objective of our study was to identify sonographic biomarkers predicting or indicating eventual malignant transformation of pathologically confirmed cirrhotic nodules. MATERIALS AND METHODS. Thirty-nine consecutive patients with 44 pathologically confirmed cirrhotic nodules (mean size, 17.5 ± 8.5 [SD] mm) who initially underwent contrast-enhanced ultrasound examination at detection and then underwent follow-up conventional ultrasound every 3-4 months thereafter were retrospectively included. Malignant transformation was identified on the basis of noninvasive diagnostic criteria for hepatocellular carcinoma or rebiopsy. Malignant transformation biomarkers were identified from clinical and sonographic variables and the performance thereof was evaluated using ROC curves. RESULTS. Fourteen nodules (31.8%) had eventual malignant transformation after a median follow-up time of 26.7 months. At initial detection, nodule size (hazard ratio [HR], 1.07; p = 0.019) and a contrast arrival time difference between the nodule and liver of more than 0.5 second (HR, 4.35; p = 0.011) were independent predictors for malignant transformation. The area under the ROC curve (Az) of initial nodule size (Az = 0.64, p = 0.131) and contrast arrival time difference between the nodule and liver (Az = 0.66, p = 0.029) improved after combining the two (Az = 0.75, p = 0.002). During follow-up, echogenicity change (p = 0.044), absolute growth rate (p < 0.001), and relative growth rate (p < 0.001) correlated with malignant transformation. Sensitivity analysis revealed that an absolute growth rate of 5 mm or greater in 6 months or a relative growth rate of 30% or greater in 6 months could be considered as threshold growth for identifying malignant transformation (specificity, 100.0%; positive predictive value, 100.0%). The absence of both echogenicity change and threshold growth was highly accurate in excluding malignant transformation (sensitivity, 100.0%; negative predictive value, 100.0%). CONCLUSION. The contrast arrival time difference between the nodule and liver at initial detection was useful in stratifying eventual malignant transformation risk for cirrhotic nodules. During follow-up, growth rate and echogenicity change correlated with malignant transformation; threshold growth on ultrasound may be considered a potential major feature in noninvasive diagnostic criteria of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) versus non-HCC: accuracy and reliability of Liver Imaging Reporting and Data System v2018.

The Liver Imaging Reporting and Data System (LI-RADS) was created to standardize the diagnostic criteria for hepatocellular carcinoma (HCC) and has undergone multiple revisions including a recent update in 2018 (v2018). The primary aim of this study was to determine the diagnostic performance and interrater reliability (IRR) of LI-RADS v2018 for distinguishing HCC from non-HCC primary hepatic malignancy in patients 'at-risk' for HCC. A secondary aim was to assess the impact of changes introduced in the v2018 diagnostic algorithm. This retrospective study combined a 10-year experience of pathologically proven primary liver malignancies from two large liver transplant centers. Two blinded readers independently evaluated each lesion and assigned a LI-RADS diagnostic category, additionally scoring all relevant imaging features. Changes in category based on the reader-provided features and the new v2018 criteria were assessed by a study coordinator. The final study cohort comprised 105 HCCs and 73 non-HCC primarily liver malignancies. LI-RADS had a high specificity for distinguishing HCC from non-HCC (89% and 90% for reader 1 and reader 2, respectively), and IRR was moderate to substantial for final LI-RADS category and most features. Revision of the LI-RADS v2018 diagnostic algorithm resulted in very few changes [5 (2.8%) and 3 (1.7%) for reader 1 and reader 2, respectively] in overall lesion classification. LI-RADS diagnostic categories and features had moderate to substantial IRR and high specificity for distinguishing HCC from non-HCC primary liver malignancy. Revision of LI-RADS v2018 diagnostic algorithm resulted in reclassification of very few lesions.

Retrospective validation of a new diagnostic criterion for hepatocellular carcinoma on gadoxetic acid-enhanced MRI: can hypointensity on the hepatobiliary phase be used as an alternative to washout with the aid of ancillary features?

To validate new diagnostic criteria for hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MR imaging (Gd-EOB-MRI) using hypointensity on the hepatobiliary phase (HBP) as an alternative to washout in combination with ancillary features. This retrospective study included 288 patients at high risk for HCC with 387 nodules (HCCs, n=292; non-HCCs, n=95) showing arterial phase hyper-enhancement (APHE) ≥1 cm on Gd-EOB-MRI. Imaging diagnoses of HCCs were made using different criteria: APHE plus hypointensity on the portal venous phase (PVP) (criterion 1), APHE plus hypointensity on the PVP and/or transitional phase (TP) (criterion 2), APHE plus hypointensity on the PVP and/or TP and/or HBP (criterion 3), and criterion 3 plus non-LR-1/2/M according to the Liver Imaging Reporting and Data System (LI-RADS) v2017 considering ancillary features (criterion 4). Sensitivities and specificities of those criteria were compared using McNemar's test. Among diagnostic criteria for HCCs, criteria 3 and 4 showed significantly higher sensitivities (93.8% and 92.5%, respectively) than criteria 1 and 2 (70.9% and 86.6%, respectively) (p values <0.001). The specificity of criterion 4 (87.4%) was shown to be significantly higher than that of criterion 3 (48.4%, p<0.001), albeit comparable to criterion 2 (86.3%, p>0.999) and significantly lower than criterion 1 (97.9%, p=0.002). In the non-invasive diagnosis of HCCs on Gd-EOB-MRI, HBP hypointensity may be used as an alternative to washout enabling a highly sensitive diagnosis with little loss in specificity if it is used after excluding nodules considered to be benignities or non-HCC malignancies based on characteristic imaging features. • Gd-EOB-MRI enhancement and ancillary features can be used to diagnose HCC. • Exclusion of LR-1/2/M improves specificity when HBP hypointensity is used.

Understanding LI-RADS, Its Relationship to AASLD and OPTN, and the Challenges of Its Adoption

Imaging-based diagnosis of hepatocellular carcinoma (HCC) is incorporated in many clinical guidelines on the management of HCC. However, there is variability in the diagnostic criteria for HCC and lack of precise definitions for imaging characteristics. With the intent of standardization and maintaining compatibility with the American Association for the Study of Liver Diseases (AASLD) and Organ Procurement and Transplantation Network (OPTN), the Liver Imaging Reporting and Data System (LI-RADS) was developed as a system for standardizing the performance, interpretation, and reporting of CT and MRI in patients at high risk of HCC. It precisely defines the terms and imaging features used in the diagnostic algorithm with the aid of a lexicon and illustrative atlas. While it is a comprehensive system, the challenges to its adoption are not trivial and can be controversial. A better understanding of the purpose and the limitation of the system can help in building consensus within and across disciplines. In this paper, we describe LI-RADS and its relationship to AASLD and OPTN guidelines. The LR-5 category is essentially equivalent to OPTN class 5 with few minor exceptions. LR-5 has been expanded to also encompass the AASLD definition of HCC. LR-4, LR-3, and LR-2 allow for more granular classification of indeterminate lesions. We highlight the advantages of the system and try to address the challenges that may impede or delay its adoption. We also review the emerging literature on its validation emphasizing that since LR-5 is designed to be specific, many HCCs will not meet LR-5 criteria and most of them will be LR-4.

Regorafenib and the RESORCE trial: a new second-line option for hepatocellular carcinoma patients.

Dr Jordi Bruix* speaks to Laura Dormer, Editorial Director: Dr Jordi Bruix is the Head of the Barcelona Clinic Liver Cancer (BCLC) group at the Hospital Clinic (University of Barcelona, Spain) and Director of the Network for Research in Liver and Digestive Disease (CIBEREHD) in the Spanish Research Institute. His research has changed the diagnosis and treatment of liver cancer. Major highlights include: development of the BCLC staging and treatment; development of diagnostic criteria for hepatocellular carcinoma; identification of the value of portal pressure in predicting prognosis after resection; and acting as principal investigator of the Phase III trials that have shown the benefits of chemoembolization, sorafenib and regorafenib for patients with liver cancer. He has authored the European Assoaciation for the Study of the Liver, American Association for the Study of Liver Diseases and World Gastroenterology Organization Practice Guidelines and the United Network for Organ Sharing hepatocellular carcinoma (HCC) diagnostic criteria.

Diagnostic criteria for hepatocellular carcinoma ⩽3 cm with hepatocyte-specific contrast-enhanced magnetic resonance imaging

Current diagnostic imaging criteria for hepatocellular carcinoma (HCC) are dedicated to imaging with nonspecific extracellular contrast agents. This study aimed to evaluate diagnostic criteria for HCC ⩽3 cm on magnetic resonance imaging (MRI) with a hepatocyte-specific contrast agent through an inception cohort study. Of 291 patients with chronic liver disease and new nodules of 1-3 cm in diameter at surveillance ultrasonography, 295 solid nodules (194 HCCs, 98 benign nodules, and three other malignancies) in 198 patients with a confirmed final diagnosis or ⩾24 months follow-up were evaluated on gadoxetic acid-enhanced MRI. Through univariate and multivariate logistic regression analyses, various diagnostic criteria were developed by combining significant MRI findings for diagnosing HCC. The diagnostic performance of each criterion was compared with that of the European Association for the Study of the Liver (EASL) criteria. Four MRI findings (arterial-phase hyperintensity, transitional-phase hypointensity, hepatobiliary-phase hypointensity, and rim enhancement) were independently significant for diagnosis of HCC ⩽3 cm. For whole nodules, EASL criteria showed the best performance for diagnosing HCC (sensitivity, 83.5%; specificity, 81.2%). For nodules ⩽2 cm in diameter, a new criterion (arterial-phase hyperintensity and hepatobiliary-phase hypointensity) showed a significantly higher sensitivity than that of the EASL criteria (83.0% vs. 74.5%, p=0.008), without a significantly different specificity (76.7% vs. 81.1%, p=0.125). EASL criteria exhibit the best diagnostic performance for HCC ⩽3 cm on hepatocyte-specific contrast-enhanced MRI. A newly identified criterion (arterial-phase hyperintensity and hepatobiliary-phase hypointensity) may increase the diagnostic sensitivity of small (⩽2 cm) HCC.