Background The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) diagnostic algorithm classifies liver observations in patients with high-risk hepatocellular carcinoma (HCC) using imaging features. However, data regarding the diagnostic performance of specific LI-RADS major feature combinations is limited. Purpose To conduct a systematic review and individual participant data (IPD) meta-analysis to establish the positive predictive values (PPVs) of LI-RADS major feature combinations using CT/MRI LI-RADS version 2018 in patients at risk for HCC. Materials and Methods Medline, Embase, Cochrane Central, and Scopus were searched for studies published from January 2014 to February 2023. Studies reporting HCC percentages for LI-RADS categories in patients at high risk for HCC were included. A one-stage random-effects IPD meta-analysis was used to calculate the PPV for HCC diagnosis and 95% CIs of major feature combinations. Wald test was used to compare combinations. Risk of bias (RoB) was assessed using Quality Assessment of Diagnostic Accuracy Studies 2, known as QUADAS-2 (protocol: https://osf.io/ah5kn). Results Forty-six studies including 6765 patients (mean age, 59 years ± 10.69 [SD]; 75% male patients [5081 of 6765]; age range, 18-93 years) with 7500 liver observations were analyzed. High RoB in at least one domain was found in 80% of studies (37 of 46). The pooled PPV estimate for major feature combinations was 58.28% in LR-3 (95% CI: 44.00, 71.29), 80.82% in LR-4 (95% CI: 71.04, 87.86), and 95.81% in LR-5 (95% CI: 91.06, 98.09). The majority of LI-RADS major feature combinations had PPVs that did not differ from others within the same category, supporting the current categorization (P value ranges: LR-3, .17-.73; LR-4, .10 to >.99; LR-5, .08 to >.99). Notably, five major feature combinations differed from the pooled PPV of the LR category. LR-3 was lower without nonrim arterial phase hyperenhancement (APHE) measuring smaller than 20 mm without additional major features (14.81%; 95% CI: 6.35, 30.85; P < .001), and higher with APHE measuring 10-19 mm without additional major features (68.33%; 95% CI: 53.94, 79.90; P = .01). LR-4 was lower without APHE measuring 20 mm or larger with enhancing capsule (50.81%; 95% CI: 28.92, 72.39; P = .009). LR-5 was lower with APHE measuring 10-19 mm with threshold growth (74.40%; 95% CI: 51.06, 89.00; P < .001), and with APHE measuring 20 mm or larger with threshold growth (82.35%; 95% CI: 57.29, 94.20; P = .02). Conclusion This meta-analysis showed that most major feature combinations in the same CT/MRI LI-RADS category had similar PPVs for HCC in patients at high risk for HCC, with the exception of five combinations within LR-3 through LR-5. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Johnson in this issue.

Differentiating the various liver tumors is pivotal due to distinct treatments and prognoses. Sometimes, it is difficult to accurately differentiate hepatocellular carcinoma (HCC) from other hepatic neoplasms non-invasively because of overlap in the triple-phase contrast-enhanced computed tomography (CECT) features, contraindication of an invasive biopsy, particularly in multifocal lesions with cirrhosis or ascites or when an MRI is unavailable or not feasible.

To assess the utility of CT perfusion (CTP) parameters in differentiating HCC from other hepatic neoplasms.

Forty-eight patients with suspicious liver lesions underwent CTP imaging. Perfusion parameters were assessed within the tumor and the adjacent normal liver using the post-processing software. Statistical significance (p-value), sensitivity, and specificity value of the individual parameters were assessed. The receiver operating characteristic (ROC) curve analysis was done to threshold values of the parameters.

The mean values of perfusion parameters like HAP (hepatic arterial perfusion), PVP (portal venous perfusion), HPI (hepatic perfusion index), BF (blood flow), BV (blood volume), MTT (mean transit time), and TTP (time to peak) were statistically significant (p-value < 0.05) between HCC and other hepatic neoplasms. Among the parameters, BV had the greatest AUC of 0.938. With a threshold value of 8.3 ml/100 ml/min, the sensitivity and specificity were 96.6% and 80%, respectively, in distinguishing HCC from other hepatic neoplasms. HPI, BF, BV, and TTP were statistically significant in differentiating hypervascular metastases from HCCs. HAP, HPI, BF, BV, and TTP were statistically significant in differentiating HCC from hypovascular metastases. BF and BV were significant in differentiating hypervascular from hypovascular metastases. HAP, PVP, HPI, BF, BV, and TTP were statistically significant in differentiating HCCs from intrahepatic cholangiocarcinomas.

CTP provides a quantitative, non-invasive method to differentiate HCC from other hepatic neoplasms with high efficacy. It can be a problem-solving tool when a conventional CECT scan cannot characterize a lesion as HCC, where biopsy is not feasible.

We aimed to develop and validate a prediction model to identify HCC in focal liver lesions (FLLs) ≤20 mm among patients at risk for HCC based on clinical and contrast-enhanced ultrasound (CEUS) features.

Between January 2022 and July 2023, 386 patients (mean age 58 ± 11 years; 277 male) at risk for HCC with FLLs ≤20 mm and clinical and preoperative CEUS data from three centers were retrospectively enrolled. Three prediction models based on clinical data (Cli-M), CEUS features (CEUS-M), and combined clinical and CEUS features (Com-M) were constructed using the training cohort (187 patients). Their predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) in the internal and external validation cohorts. All patients were reclassified using the American College of Radiology CEUS Liver Imaging Reporting and Data System (CEUS LI-RADS) and combined with the best-performing model (modified LI-RADS).

The AUCs of Com-M were 0.873-0.951 in the training, internal, and external validation cohorts, which were higher than those of Cli-M (0.749-0.795, all P < 0.05) and CEUS-M (0.848-0.899, all P < 0.05). The sensitivity of LR-5 of modified LI-RADS was significantly improved from 83.1 % to 88.9 % (p＜0.001) in the training, internal and external validation cohort while there was no statistical different on its specificity (82.6 %-94.7 % vs 95.7 %-97.6 %., p = 0.162-0.650).

The model based on clinical and CEUS features can help identify HCC in FLLs ≤ 20 mm in high-risk patients.

Microvascular invasion (MVI) affects the prognosis and treatment of hepatocellular carcinoma (HCC); however, its preoperative diagnosis is challenging. Analysis of computed tomography (CT) images using radiomics can detect MVI, but its effectiveness depends on the imaging conditions. We compared the efficacies of radiomics, clinical, and combined models for predicting MVI in HCC using nonstandardized scanning protocols.

This multicenter study included 533 patients who underwent hepatic resection for HCC. Patients were divided randomly into training (n = 426) and test groups (n = 107). We manually extracted 3D CT features in hepatic arterial, portal venous, and venous phases. The radiomics model was trained by machine learning. A logistic regression model was developed based on clinical information, and a fused model was created integrating clinical information and radiomics prediction score (Rad_Score). We calculated areas under the receiver operating characteristic curves (AUCs) for the radiomics, clinical, and mixed models in the test groups.

The clinical model incorporated hepatitis B virus surface antigen, tumor diameter, and log-transformed α-fetoprotein and des-gamma-carboxyprothrombin. The AUCs of the radiomics and clinical models were comparable (p = 0.76). Rad_Score was not an independent significant factor in the fused model (p = 0.40) and its addition did not improve the accuracy of the clinical model alone (p = 0.51).

A clinical model is as effective as a CT radiomics model for predicting MVI status in patients with HCC based on real-world scanning data, and integration of both models does not improve the predictive performance compared with a clinical model alone.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, often diagnosed at advanced stages due to insufficient early screening and monitoring. MicroRNAs (miRNAs) are key regulators of gene expression and potential biomarkers for cancer diagnosis. This study investigated the diagnostic potential of miRNAs in Extracellular Vesicles (EVs) from HCC. miRNA expression in EVs was analyzed using HCC cell lines, circulating EVs from a Diethylnitrosamine (DEN)-induced liver tumor rat model, and plasma samples from HCC patients. Receiver Operating Characteristics (ROCs) were applied to evaluate the diagnostic accuracy of circulating EV miRNAs in patients. Five miRNAs (miR-183-5p, miR-19a-3p, miR-148b-3p, miR-34a-5p, and miR-215-5p) were consistently up-regulated in EVs across in vitro and in vivo HCC models. These miRNAs showed statistically significant differences in HCC patients stratified by TNM staging and Edmondson-Steiner grading compared to healthy controls. They also differentiated HCC patients with various etiologies from the control group and distinguished HCC patients, with or without liver cirrhosis, from cirrhotic and healthy individuals. Individually and as a panel, they demonstrated high sensitivity, specificity, and accuracy in identifying HCC patients. Their consistent upregulation across models and clinical samples highlights their robustness as biomarkers for HCC diagnosis, offering the potential for early disease management and prognosis.

Many guidelines for hepatocellular carcinoma (HCC) have been published and are regularly updated worldwide. HCC management involves a broad range of treatment options and requires multidisciplinary care, resulting in significant heterogeneity in management practices across international communities. To support standardized care for HCC, we systematically appraised 13 globally recognized guidelines and expert consensus statements, including five from Asia, four from Europe, and four from the United States. These guidelines share similarities but reveal notable discrepancies in surveillance strategies, treatment allocation, and other recommendations. Geographic differences in tumor biology (e.g., prevalence of viral hepatitis, alcohol-related liver disease, or metabolic dysfunction-associated steatotic liver disease) and disparities in available medical resources (e.g., organ availability, healthcare infrastructure, and treatment accessibility) complicate the creation of universally applicable guidelines. Previously, significant gaps existed between Asian and Western guidelines, particularly regarding treatment strategies. However, these differences have diminished over the years. Presently, variations are often more attributable to publication dates than to regional differences. Nonetheless, Asia-Pacific experts continue to diverge from the Barcelona Clinic Liver Cancer system, particularly with respect to surgical resection and locoregional therapies, which are viewed as overly conservative in Western guidelines. Advancements in systemic therapies have prompted ongoing updates to these guidelines. Given that each set of guidelines reflects distinct regional characteristics, strengths, and limitations, fostering collaboration and mutual complementarity is essential for addressing discrepancies and advancing global HCC care.

Our study aimed to develop a machine learning (ML) model utilizing grayscale ultrasound (US) to distinguish ≤3 cm small hepatocellular carcinoma (sHCC) from non-HCC lesions.

A total of 1052 patients with 1058 liver lesions ≤3 cm from 55 hospitals were collected between May 2017 and June 2021, and 756 liver lesions were randomly allocated into train and internal validation cohorts at a 8:2 ratio for the development and evaluation of ML models based on multilayer perceptron (MLP) and extreme gradient boosting (XGBoost) methods (ModelU utilizing US imaging features; ModelUR adding US radiomics features; ModelURC employing clinical features further). The diagnostic performance of three models was assessed in external validation cohort (312 liver lesions from 14 hospitals). The diagnostic efficacy of the optimal model was compared to that of radiologists in external validation cohort. The SHapley Additive exPlanations (SHAP) method was employed to interpret the optimal ML model by ranking feature importance. The study was registered at ClinicalTrials.gov (NCT03871140).

ModelURC based XGBoost showed the best performance (AUC = 0.934; 95% CI: 0.894-0.974) in the internal validation cohort. In the external validation cohort, ModelURC also achieved optimal AUC (AUC = 0.899, 95% CI: 0.861-0.931). Upon conducting a subgroup analysis, no statistically significant differences were observed in the diagnostic performance of the ModelURC neither between tumor sizes of ≤2.0 cm and 2.1-3.0 cm nor across different HCC risk stratifications. ModelURC exhibited superior ability compared to all radiologists and ModelURC assistance significantly improved the diagnostic AUC for all radiologists (all P < 0.0001).

A diagnostic model for sHCC was developed and validated using ML and grayscale US from large cohorts. This model significantly improved the diagnostic performance of grayscale US for sHCC compared with experts.

This work was supported by National Key Research and Development Program of China (2022YFC2405500), Major Research Program of the National Natural Science Foundation of China (92159305), National Science Fund for Distinguished Young Scholars (82325027), Key project of National Natural Science Foundation of China (82030047), Military Fund for Geriatric Diseases (20BJZ42), National Natural Science Foundation of China Special Program (82441011). National Natural Science Foundation of China (82402280), National Natural Science Foundation of China (32171363), Key Research and Development Program for Social Development of Yunnan Science and Technology Department (202403AC100014).

The American College of Radiology Liver Imaging Reporting and Data System (LI-RADS) is the preeminent framework for classification and risk stratification of liver observations on imaging in patients at high risk for hepatocellular carcinoma. In this review, the pathogenesis of hepatocellular carcinoma and the use of MRI in LI-RADS is discussed, including specifically the LI-RADS diagnostic algorithm, its components, and its reproducibility with reference to the latest supporting evidence. The LI-RADS treatment response algorithms are reviewed, including the more recent radiation treatment response algorithm. The application of artificial intelligence, points of controversy, LI-RADS relative to other liver imaging systems, and possible future directions are explored. After reading this article, the reader will have an understanding of the foundation and application of LI-RADS as well as possible future directions.

Liver cancer seriously threatens the health of human beings. Studies have found that esterase is overexpressed in liver cancer cells. Therefore, esterase can be one of the biomarkers of liver cancer. Previous literature studies have shown that the structures of fluorescent probe detection groups significantly impact the probes themselves and enzyme detection. In this paper, three "off-on" esterase-activated fluorescent probes (RHO-1, RHO-2 and RHO-3) with different length of the carbon chains of the detection groups were designed and synthesized. Density functional theory (DFT) calculation and Michaelis-Menten equations were applied to study the optical properties and affinity with esterase of the probes. Compared with RHO-1 and RHO-2, RHO-3 showed superior optical properties and affinity with esterase. Subsequently, RHO-3 was further used to detect esterase activity in vitro and in vivo. RHO-3 was the first esterase-activated fluorescent probe applied to image-guided diagnosis and surgical resection of liver cancer. It was expected to be a promising molecular imaging diagnostic tool in clinical applications.

Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.

To determine the diagnostic value of ultrasound, multi-phase enhanced computed tomography, and magnetic resonance imaging of small hepatocellular carcinoma.

Experimental studies on diagnosing small hepatocellular carcinoma in four databases: PubMed, Cochrane Library, Web of Science, and Embase, were comprehensively searched from October 2007 to October 2024. Relevant diagnostic accuracy data were extracted and a Bayesian model that combined direct and indirect evidence was used for analysis.

16 original studies were included and data from 2,447 patients were collated to assess the diagnostic value of 10 different methods. The methodological quality of the included studies was good and there was no obvious publication bias. The pooled DOR of all diagnostic methods was 19.61, which was statistically significant (I2 = 76.0%, P < 0.01, 95% CI:13.30 - 28.92). Normal US + CEUS + ultrasonic elastic imaging had the highest specificity (92.9), accuracy (93.6), and positive predictive value (94.4). Unenhanced MRI + Contrast-enhanced MRI had the highest sensitivity (96.6) and negative predictive value (96.6), but specificity (12.5) and positive predictive value (34.4) were extremely poor. Contrast-enhanced MRI had the highest diagnostic value in individual imaging methods (sensitivity: 66, specificity: 55.5, accuracy: 67.9, positive predictive value: 64.4, negative predictive value: 66.5). There was significant inconsistency and high heterogeneity in this study.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024507883.

Initially released in 2011, liver imaging reporting and data (LI-RADS) CT/MRI diagnostic algorithm categorizes hepatic observations on an ordinal scale based on the probability of hepatocellular carcinoma, malignancy, or benignity, and guides reproducible interpretation, clear communication, and standardized terminology for liver imaging. LI-RADS has significantly expanded in scope in the past decade, with the inclusion of algorithms that address screening and surveillance, diagnosis with contrast enhanced ultrasound (CEUS), and treatment response assessment with both CEUS and CT/MRI. LI-RADS algorithms undergo periodic refinements based on accumulating scientific evidence, user feedback, and technological advancements. This manuscript discusses recent LI-RADS algorithm refinements, planned updates, with a focus on LI-RADS CT/MRI diagnostic algorithm, and future goals.

To perform an intra-individual comparison of LI-RADS category and imaging features in patients at high risk of hepatocellular carcinoma (HCC) on contrast-enhanced CT, gadoxetate disodium-enhanced MRI (EOB-MRI), and extracellular agent-enhanced MRI (ECA-MRI) and to analyze the diagnostic performance of each imaging modality.

This retrospective study included cirrhotic patients with at least one LR-3, LR-4, LR-5, LR-M or LR-TIV observation imaged with at least two imaging modalities among CT, EOB-MRI, or ECA-MRI. Two radiologists evaluated the observations using the LI-RADS v2018 diagnostic algorithm. Reference standard included pathologic confirmation and imaging criteria according to LI-RADS v2018. Imaging features were compared between different exams using the McNemar test. Inter-modality agreement was calculated by using the weighted Cohen's kappa (k) test.

A total of 144 observations (mean size 34.0 ± 32.4 mm) in 96 patients were included. There were no significant differences in the detection of major and ancillary imaging features between the three imaging modalities. When considering all the observations, inter-modality agreement for category assignment was substantial between CT and EOB-MRI (k 0.60; 95%CI 0.44, 0.75), moderate between CT and ECA-MRI (k 0.46; 95%CI 0.22, 0.69) and substantial between EOB-MRI and ECA-MRI (k 0.72; 95%CI 0.59, 0.85). In observations smaller than 20 mm, inter-modality agreement was fair between CT and EOB-MRI (k 0.26; 95%CI 0.05, 0.47), moderate between CT and ECA-MRI (k 0.42; 95%CI -0.02, 0.88), and substantial between EOB-MRI and ECA-MRI (k 0.65; 95%CI 0.47, 0.82). ECA-MRI demonstrated the highest sensitivity (70%) and specificity (100%) when considering LR-5 as predictor of HCC.

Inter-modality agreement between CT, ECA-MRI, and EOB-MRI decreases in observations smaller than 20 mm. ECA-MRI has the provided higher sensitivity for the diagnosis of HCC.

Guidelines recommend that sub-centimeter nodules on ultrasound be followed with short-interval surveillance ultrasound, given assumed low risk of hepatocellular carcinoma (HCC) and suboptimal diagnostic imaging performance in lesions <1 cm. We performed a systematic review to estimate HCC risk among patients with cirrhosis and sub-centimeter nodules detected on ultrasound.

We systematically searched Ovid MEDLINE and EMBASE databases for relevant articles published between January 2005 and July 2024. A random-effects model was used to calculate the pooled proportion of incident HCC.

We identified 9 eligible studies, of which 5 provided both lesion- and patient-level data (n = 354 patients), 2 patient-level alone (n = 888 patients), and 2 lesion-level alone (n = 69 lesions). The pooled proportion of incident HCC was 31.9% (95% confidence interval [CI], 8.7%-69.7%) on a lesion-level and 21.3% (95% CI, 6.0%-53.6%) on a patient-level; however, pooled estimates were limited by high heterogeneity (I2 >90%). Among 2 studies with study periods post-dating 2015, HCC developed in only ∼5% of patients during a median follow-up of 2 years. Risk factors associated with incident HCC were older age, male sex, elevated alpha-fetoprotein levels, thrombocytopenia, and Child Pugh B cirrhosis. Limitations of studies included small sample sizes, selection bias, ascertainment bias for HCC, and failure to report factors associated with HCC.

Up to one-fifth of patients with sub-centimeter nodules may develop HCC, although contemporary cohorts report a substantially lower risk. Older patients and those with elevated alpha-fetoprotein levels or poorer liver function are at greatest risk of HCC, highlighting an unmet need for better risk stratification models.

Cirrhotic liver nodules can progress to hepatocellular carcinoma (HCC) through a multi-step carcinogenesis model, with dysplastic nodules being particularly high risk. Currently, monitoring the progression of non-HCC cirrhotic nodules is primarily through dynamic observation, but there is a lack of sensitive, efficient, and convenient methods. Dynamic monitoring and risk evaluation of malignant transformation are essential for timely treatment and improved patient survival rates. Routine liver biopsies are impractical for monitoring, and imaging techniques like ultrasound, computed tomography, and magnetic resonance imaging are not suitable for all patients or for accurately assessing subcentimeter nodules. Identifying serum biomarkers with high sensitivity, specificity, and stability, and developing a multi-index evaluation model, may provide a more convenient and efficient approach to monitoring pathological changes in cirrhotic nodules.

To investigate whether a deep learning (DL) controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-volumetric interpolated breath-hold examination (VIBE) technique can improve image quality, lesion conspicuity, and lesion detection compared to a standard CAIPIRINHA-VIBE technique in gadoxetic acid-enhanced liver MRI.

This retrospective single-center study included 168 patients who underwent gadoxetic acid-enhanced liver MRI at 3 T using both standard CAIPIRINHA-VIBE and DL CAIPIRINHA-VIBE techniques on pre-contrast and hepatobiliary phase (HBP) images. Additionally, high-resolution (HR) DL CAIPIRINHA-VIBE was obtained with 1-mm slice thickness on the HBP. Three abdominal radiologists independently assessed the image quality and lesion conspicuity of pre-contrast and HBP images. Statistical analyses involved the Wilcoxon signed-rank test for image quality assessment and the generalized estimation equation for lesion conspicuity and detection evaluation.

DL and HR-DL CAIPIRINHA-VIBE demonstrated significantly improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE (p < 0.001), with a shorter acquisition time (DL vs standard, 11 s vs 17 s). However, the former presented a more synthetic appearance (both p < 0.05). HR-DL CAIPIRINHA-VIBE showed superior lesion conspicuity to standard and DL CAIPIRINHA-VIBE on HBP images (p < 0.001). Moreover, HR-DL CAIPIRINHA-VIBE exhibited a significantly higher detection rate of small (< 2 cm) solid focal liver lesions (FLLs) on HBP images compared to standard CAIPIRINHA-VIBE (92.5% vs 87.4%; odds ratio = 1.83; p = 0.036).

DL and HR-DL CAIPIRINHA-VIBE achieved superior image quality compared to standard CAIPIRINHA-VIBE. Additionally, HR-DL CAIPIRINHA-VIBE improved the lesion conspicuity and detection of small solid FLLs. DL and HR-DL CAIPIRINHA-VIBE hold the potential clinical utility for gadoxetic acid-enhanced liver MRI.

DL and HR-DL CAIPIRINHA-VIBE hold promise as potential alternatives to standard CAIPIRINHA-VIBE in routine clinical liver MRI, improving the image quality and lesion conspicuity, enhancing the detection of small (< 2 cm) solid focal liver lesions, and reducing the acquisition time.

• DL and HR-DL CAIPIRINHA-VIBE demonstrated improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE, in addition to a shorter acquisition time. • DL and HR-DL CAIPIRINHA-VIBE yielded a more synthetic appearance than standard CAIPIRINHA-VIBE. • HR-DL CAIPIRINHA-VIBE showed improved lesion conspicuity than standard CAIPIRINHA-VIBE on HBP images, with a higher detection of small (< 2 cm) solid focal liver lesions.

The early diagnosis of hepatocellular carcinomas (HCCs) remains challenging in the clinic. Primovist-enhanced magnetic resonance imaging (MRI) aids HCC diagnosis but loses sensitivity for tumors <2 cm. Therefore, developing advanced MRI contrast agents is imperative for improving the diagnostic accuracy of HCCs in very-early-stage. To address this challenge, PEGylated ultra-small iron oxide nanoparticles (PUSIONPs) are synthesized and employed as liver-specific T1 MRI contrast agents. Intravenous delivery produces simultaneous hyperintense HCC and hypointense hepatic parenchyma signals on T1 imaging, creating an extraordinarily high tumor-to-liver contrast. Systematic studies uncover PUSIONP distribution in hepatic parenchyma, HCC lesions at the organ, tissue, cellular, and subcellular levels, revealing endosomal confinement of PUSIONP without aggregation. By mimicking such situations, the dependency of relaxometric properties on local PUSIONP concentration is investigated, emphasizing the key role of different endosomal concentrations in liver and tumor cells for high tumor-to-liver contrast and clear tumor boundaries. These findings offer exceptional imaging capabilities for early HCC diagnosis, potentially benefiting real HCC patients.

In patients evaluated for hepatocellular carcinoma (HCC), magnetic resonance imaging (MRI) is often used secondarily when multiphase contrast-enhanced computed tomography (ceCT) is inconclusive. We investigated the clinical impact of adding MRI.

This single-institution retrospective study included 48 MRI scans (44 patients) conducted from May 2016 to July 2023 due to suspicion of HCC on a multiphase ceCT scan. Data included medical history, preceding and subsequent imaging, histology when available, and decisions made at multidisciplinary team meetings.

In case of possible HCC recurrence, 63% of the MRI scans were diagnostic of HCC. For 80% of the negative MRI scans, the patients were diagnosed with HCC within a median of 165 days in the suspicious area of the liver. In case of possible de-novo HCC in patients with cirrhosis, 22% of the scans were diagnostic of HCC and 33% of the negative MRI scans were of patients diagnosed with HCC within a median of 109 days. None of the non-cirrhotic patients with possible de-novo HCC and negative MRI scans (64%) were later diagnosed with HCC, but 3/5 of the indeterminate scans were of patients diagnosed with HCC in a biopsy.

Secondary MRI to a multiphase ceCT scan suspicious of HCC is highly valuable in ruling out HCC in non-cirrhotic patients and in diagnosing HCC non-invasively in cirrhotic patients and patients with prior HCC. Patients with cirrhosis or prior HCC are still at high risk of having HCC if MRI results are inconclusive or negative.

A high baseline NLR is associated with a poor prognosis of immunotherapy in patients with advanced HCC. As anti-tumour immune activation takes time, early dynamic changes in NLR may serve as a biomarker for predicting immunotherapy response. We conducted a retrospective study in which we enrolled 209 patients with aHCC who received ICIs (training cohort: N = 121, validation cohort: N = 88). In the training cohort, we categorized the patients based on the early changes in their NLR. Specifically, we defined patients as NLR Stable-Responder, NLR Responder and NLR Non-Responder. We compared the outcomes of these three patient groups using survival analysis. Additionally, we shortened the observation period to 6 weeks and validated the findings in the validation cohort. In the training cohort, early dynamic changes in NLR (HR 0.14, 95%CI 0.03-0.65, p = 0.012, HR 0.19, 95%CI 0.07-0.54, p = 0.002; HR 0.21, 95%CI 0.10-0.42, p < 0.001, HR 0.40, 95%CI 0.23-0.69, p = 0.001), PD-L1 < 1% (HR 5.36, 95%CI 1.12-25.66, p = 0.036; HR 2.98, 95%CI 1.51-5.91, p = 0.002) and MVI (HR 3.52, 95%CI 1.28-9.69, p = 0.015; HR 1.99, 95%CI 1.14-3.47, p = 0.015) were identified as independent predictors of OS and PFS. In the validation cohort, when the observation period was reduced to 6 weeks, early NLR changes still have predictive value. Early dynamic changes in NLR may be an easily defined, cost-effective, non-invasive biomarker to predict aHCC response to ICIs.

An incidental focal liver lesion (IFLL) is defined as a hepatic lesion identified in a patient imaged for an unrelated reason. They are frequently encountered in daily practice, sometimes leading to unnecessary, invasive and potentially harmful follow-up investigations. The clinical presentation and the imaging aspects play an important role in deciding if, and what further evaluation, is needed. In low-risk patients (i.e., without a history of malignant or chronic liver disease or related symptoms), especially in those younger than 40 years old, more than 95% of IFLLs are likely benign. Shear Wave liver Elastography (SWE) of the surrounding liver parenchyma should be considered to exclude liver cirrhosis and for further risk stratification. If an IFLL in a low-risk patient has a typical appearance on B-mode ultrasound of a benign lesion (e.g., simple cyst, calcification, focal fatty change, typical hemangioma), no further imaging is needed. Contrast-Enhanced Ultrasound (CEUS) should be considered as the first-line contrast imaging modality to differentiate benign from malignant IFLLs, since it has a similar accuracy to contrast-enhanced (CE)-MRI. On CEUS, hypoenhancement of a lesion in the late vascular phase is characteristic for malignancy. CE-CT should be avoided for characterizing probable benign FLL and reserved for staging once a lesion is proven malignant. In high-risk patients (i.e., with chronic liver disease or an oncological history), each IFLL should initially be considered as potentially malignant, and every effort should be made to confirm or exclude malignancy. US-guided biopsy should be considered in those with unresectable malignant lesions, particularly if the diagnosis remains unclear, or when a specific tissue diagnosis is needed.

Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.

Combined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels.

We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET/CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET/CT in diagnosing HCC were evaluated. A multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed.

Dual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n = 273, κ = 0.822; 95% CI 0.803-0.864).

Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

Compared to CT or MRI, dual-tracer positron-emission tomography/computed tomography (PET/CT) led to upstaging in 12% of patients with hepatocellular carcinoma (HCC) undergoing staging, resulting in treatment modification in 8% of cases and a cost saving of US$495 per patient. It also accurately detected HCC in high-risk cases where CT or MRI were equivocal or normal. Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

Notably, the number of incidentally detected focal liver lesions (FLLs) has increased dramatically in recent years due to the increased use of radiological imaging. The diagnosis of FLLs can be made through a well-documented medical history, physical examination, laboratory tests, and appropriate imaging methods. Although benign FLLs are more common than malignant ones in adults, even in patients with primary malignancy, accurate diagnosis of incidental FLLs is of utmost clinical significance. In clinical practice, FLLs are frequently evaluated non-invasively using ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). Although US is a cost-effective and widely used imaging method, its diagnostic specificity and sensitivity for FLL characterization are limited. FLLs are primarily characterized by obtaining enhancement patterns through dynamic contrast-enhanced CT and MRI. MRI is a problem-solving method with high specificity and sensitivity, commonly used for the evaluation of FLLs that cannot be characterized by US or CT. Recent technical advancements in MRI, along with the use of hepatobiliary-specific MRI contrast agents, have significantly improved the success of FLL characterization and reduced unnecessary biopsies. The American College of Radiology (ACR) appropriateness criteria are evidence-based recommendations intended to assist clinicians in selecting the optimal imaging or treatment option for their patients. ACR Appropriateness Criteria Liver Lesion-Initial Characterization guideline provides recommendations for the imaging methods that should be used for the characterization of incidentally detected FLLs in various clinical scenarios. The American College of Gastroenterology (ACG) Clinical Guideline offers evidence-based recommendations for both the diagnosis and management of FLL. American Association for the Study of Liver Diseases (AASLD) Practice Guidance provides an approach to the diagnosis and management of patients with hepatocellular carcinoma. In this article, FLLs are reviewed with a comprehensive analysis of ACR Appropriateness Criteria, ACG Clinical Guideline, AASLD Practice Guidance, and current medical literature from peer-reviewed journals. The article includes a discussion of imaging methods used for the assessment of FLL, current recommended imaging techniques, innovations in liver imaging, contrast agents, imaging features of common nonmetastatic benign and malignant FLL, as well as current management recommendations.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in China. The combination of immune checkpoint inhibitors (ICIs) and antiangiogenic drugs, such as bevacizumab and tyrosine kinase inhibitors, has been recommended as first-line treatment for advanced HCC. However, two-thirds of patients did not benefit from this form of immunotherapy. Currently, data on the subsequent regimen for patients previously treated with ICIs are lacking. Studies have shown that the combination of radiotherapy (RT) and ICIs is a potentially effective second-line therapy for HCC. This study aims to assess the efficacy and safety of combined therapy with stereotactic body RT (SBRT), sintilimab and IBI305 (a biosimilar of bevacizumab) in patients with HCC following the progression of first-line ICI therapy.

This study is an open-label, single-arm, single-centre, phase 2 trial of 21 patients with advanced HCC in whom previous ICI therapy has failed. Participants will receive approximately 30-40 Gy/5-8F SBRT, followed by 200 mg sintilimab and 15 mg/kg IBI305 intravenously every 3 weeks. Treatment will continue until the development of unacceptable toxicity or disease progression. We will use Simon's two-stage design, with the objective response rate (ORR) as the primary endpoint. Secondary endpoints include ORR of lesions without RT, disease control rate, progression-free survival, overall survival and safety.

The study was authorised by the Medical Ethics Committee. Dissemination of results will occur via a peer-reviewed publication and other relevant media.

ChiCTR2200056068.

The recognition of arterial phase hyperenhancement (APHE) and washout during the late phase is key for correct diagnosis of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS). This meta-analysis was conducted to compare SonoVue®-enhanced and Sonazoid®-enhanced ultrasound in the assessment of HCC enhancement and diagnosis.

Studies were included in the analysis if they reported data for HCC enhancement in the arterial phase and late phase for SonoVue® or in the arterial phase and Kupffer phase (KP) for Sonazoid®. Forty-two studies (7502 patients) with use of SonoVue® and 30 studies (2391 patients) with use of Sonazoid® were identified. In a pooled analysis, the comparison between SonoVue® and Sonazoid® CEUS was performed using chi-square test. An inverse variance weighted random-effect model was used to estimate proportion, sensitivity, and specificity along with 95% confidence interval (CI).

In the meta-analysis, the proportion of HCC showing APHE with SonoVue®, 93% (95% CI 91-95%), was significantly higher than the proportion of HCC showing APHE with Sonazoid®, 77% (71-83%) (p < 0.0001); similarly, the proportion of HCC showing washout at late phase/KP was significantly higher with SonoVue®, 86% (83-89%), than with Sonazoid®, 76% (70-82%) (p < 0.0001). The sensitivity and specificity for the detection of APHE plus late-phase/KP washout detection in HCC were also higher with SonoVue® than with Sonazoid® (sensitivity 80% vs 52%; specificity 80% vs 73% in studies within unselected patient populations).

APHE and late washout in HCC are more frequently observed with SonoVue® than with Sonazoid®. This may affect the diagnostic performance of CEUS in the diagnosis of HCCs.

Meta-analysis data show the presence of key enhancement features for diagnosis of hepatocellular carcinoma is different between ultrasound contrast agents, and arterial hyperenhancement and late washout are more frequently observed at contrast-enhanced ultrasound with SonoVue® than with Sonazoid®.

• Dynamic enhancement features are key for imaging-based diagnosis of HCC. • Arterial hyperenhancement and late washout are more often observed in HCCs using SonoVue®-enhanced US than with Sonazoid®. • The existing evidence for contrast-enhanced US may need to be considered being specific to the individual contrast agent.

We conducted a comprehensive review of the current literature of published data and clinical trials (MEDLINE), as well as published congress contributions and active recruiting clinical trials on targeted therapies in hepatocellular carcinoma. Combinations of different agents and medical therapy along with radiological interventions were analyzed for the setting of advanced HCC. Those settings were also analyzed in combination with adjuvant situations after resection or radiological treatments. We summarized the current knowledge for each therapeutic setting and combination that currently is or has been under clinical evaluation. We further discuss the results in the background of current treatment guidelines. In addition, we review the pathophysiological mechanisms and pathways for each of these investigated targets and drugs to further elucidate the molecular background and underlying mechanisms of action. Established and recommended targeted treatment options that already exist for patients are considered for systemic treatment: atezolizumab/bevacizumab, durvalumab/tremelimumab, sorafenib, lenvatinib, cabozantinib, regorafenib, and ramucirumab. Combination treatment for systemic treatment and local ablative treatment or transarterial chemoembolization and adjuvant and neoadjuvant treatment strategies are under clinical investigation.

To retrospectively evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) LI-RADS in liver nodules < 20 mm at high risk of hepatocellular carcinoma (HCC) and their correlation with clinic-pathological features.

A total of 432 pathologically proved liver nodules < 20 mm were included from January 2019 to June 2022. Each nodule was categorized as LI-RADS grade (LR)-1 to LR-5 through LR-M according to CEUS LI-RADS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of CEUS LI-RADS were evaluated using pathological reference standard. Correlations between clinic-pathological features and CEUS LI-RADS categorization, together with major CEUS features, were further explored.

With LR-5 to diagnose HCC, the sensitivity, specificity, PPV, NPV, and AUC were 50.3%, 70.0%, 91.2%, 18.5%, and 0.601, respectively. The proportion of LR-5 in primary HCCs was significantly higher than that in recurrent ones (p = 0.014). HCC 10-19 mm showed significantly more frequent arterial phase hyper-enhancement (APHE) and late washout (p < 0.05) and less no-washout (p = 0.003) compared with those in HCC < 10 mm. Well-differentiated HCCs showed more frequent non-APHE and no-washout than moderate- and poor-differentiated HCCs (p < 0.05). Upgrading "APHE without washout" LR-4 nodules 10-19 mm with HCC history and "APHE with late mild washout" LR-4 nodules < 10 mm to LR-5 could improve the diagnostic performance of LR-5. The corresponding sensitivity, specificity, PPV, NPV, and AUC are 60.2%, 70.0%, 92.6%, 22.1%, and 0.651, respectively.

CEUS LI-RADS is valuable in the diagnosis of HCC < 20 mm and performance can be improved with the combination of clinic-pathological features.

CEUS LI-RADS was valuable in the diagnosis of HCC < 20 mm and its diagnostic performance can be improved by combining clinic-pathological features. Further research is needed to define its value in this set of lesions.

Contrast-enhanced ultrasound can detect small liver lesions where LI-RADS accuracy is uncertain. Many LI-RADS Grade-4 nodules were upgraded to Grade-5 by combining imaging with clinic-pathological factors. The reclassification of LI-RADS Grade-5 can improve sensitivity without decreasing positive predictive value.

The objective of our study was to study and compare the sonographic findings of hepatocellular carcinoma (HCC) and benign liver lesions, and apply these to an HCC surveillance program in patient with chronic hepatitis B virus (HBV).

Sonographic findings of HCC and benign liver lesions were retrospectively reviewed following diagnosis based on either computer tomography or magnetic resonance imaging from July 2010 to December 2020. Multiple sonographic features were analyzed, including internal echogenicity, rim characteristics, and posterior acoustic enhancement. Associations between sonographic characteristics and HCC were assessed using uni- and multi-variate logistic regression analyses.

Of the focal liver lesions in 337 chronic HBV patients, there were 25 HCC and 410 benign lesions, with median sizes of 1.6 and 1.0 cm, respectively. Three ultrasound patterns, homogeneous hypoechogenicity, heterogeneous echogenicity, and hypoechoic rims were more frequently found in HCC than in benign lesions. Moreover, the hypoechoic rim feature was the only sonographic pattern independently associated with HCC (Odds ratio, 68.05; 95% confidence interval, 7.37-628.10; p-values < 0.001). In a subgroup analysis of the lesions sized 2 cm or smaller, no sonographic findings were associated with HCC.

A hypoechoic rim was a sonographic feature independently associated with HCC. These findings may aid in improving HCC detection and guiding management during HCC screening and surveillance with ultrasound.

Since the adoption of guidelines for the non-invasive imaging diagnosis of hepatocellular carcinoma (HCC), the need for sampling of a lesion in cirrhosis has decreased. We aimed to retrospectively investigate the use of percutaneous imaging-guided biopsy for LI-RADS observations in cirrhosis in two large liver transplant centers. A review of the pathology database in the two Institutions (Institution A, Institution B) was conducted to identify patients that underwent percutaneous imaging-guided biopsy for a liver lesion in the interval time 01/01/2015-12/312020. Liver observations on pre-procedure contrast-enhanced CT or MRI were classified according to LI-RADS v2018. Among the 728 patients who underwent imaging guided biopsy of a liver lesion in Institution A, and among the 749 patients who underwent imaging guided biopsy of a liver lesion in Institution B, respectively 50 (6.8 %) and 16 (2.1 %) were cirrhotic with available pre-procedural contrast-enhanced CT or MRI. A total of 67 lesions were biopsied. 30/67 (45 %) biopsied observations were classified as LR-M. 55/67 (82 %) biopsies were positive for malignancy at histopathology and among them 33 (60 %) were HCC. In conclusion, a small percentage of percutaneous, imaging-guided biopsies for liver lesions are performed in cirrhosis, and more frequently for LR-M observations.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, including Australia. The absence of a consensus clinical practice guideline (CPG) specific to HCC management poses challenges in reducing morbidity, mortality, and improving patient recovery. This systematic review aims to evaluate the existing evidence and assess the potential of published guidelines, including those with an international scope, to provide guidance for healthcare professionals in Australia.

Electronic search of MEDLINE, Embase, Cochrane Library, Google Scholar, and PubMed was conducted. Peer-reviewed English language articles from 2005 to June 2022 were included if they described management of HCC as part of an evidence-based overall management plan or CPG. The quality of the included CPGs was assessed by the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool.

Twenty-one articles from 16 regions throughout the world were included in this review. All included guidelines (n = 21, 100%) recommended evaluating cirrhosis, hepatitis B, and hepatitis C as potential risk factors of HCC. Obesity and non-alcoholic fatty liver disease were recommended by 19 CPGs (91%) as risk factor for HCC. Fourteen guidelines (67%) endorsed using the BCLC staging system. Eighteen guidelines (86%) recommended a multidisciplinary approach for the management of HCC. Eighteen guidelines (86%) advised that surveillance using ultrasound should be implemented in all cirrhotic patients every 6 months regardless of the cause of cirrhosis. AGREE II mean overall assessment score was 90% indicating that all guidelines included were highly recommended in majority of domains.

The included CPGs provided a comprehensive approach, emphasizing the evaluation of risk factors, utilization of the BCLC staging system, and the importance of a multidisciplinary approach. Regular surveillance using ultrasound for cirrhotic patients was widely recommended. An understanding of contemporary international CPGs can prioritize aspects of the management of HCC to assist healthcare professionals to develop a national guideline to enable standardized, comprehensive, and evidence-based care for patients with HCC.

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists' F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.

The purpose of this study was to investigate the added value of color parameter imaging (CPI) in the differential diagnosis of focal liver lesions (FLLs) with "homogeneous hyperenhancement but not wash out" on contrast-enhanced ultrasound (CEUS).

A total of 101 patients with 108 FLLs were enrolled in this study. All the FLLs received US and CEUS examinations. The stored CEUS clips of target lesions were postprocessed with CPI analysis by radiologists. The receiver operator characteristic (ROC) curve was used to evaluate the added value of CPI. The McNamara test was used to compare the diagnostic sensitivity, specificity, and accuracy between CEUS and CPI patterns. Univariate and multivariate logistic regression analyses were used to develop a CPI nomogram. The C index and calibration curve were used to evaluate the predictive ability of the nomogram. The intraclass correlation coefficient was used to test the reproducibility and reliability of CPI. Decision curve analysis (DCA) was used to evaluate the added value of applying CPI.

The following CPI features were more frequently observed in malignant FLLs: eccentric perfusion (malignant: 70.0% vs. benign: 29.2%, p < 0.001), feeding artery (51.7% vs. 4.2%, p < 0.001), mosaic (63.3% vs. 6.3%, p < 0.001), red ingredients >1/3 (90.0% vs. 14.6%, p < 0.001). In addition, centripetal (43.8% vs. 18.3%, p = 0.004), peripheral nodular (54.2% vs. 1.7%, p < 0.001), subcapsular vessel (12.5% vs. 0.0%, p = 0.004), spoke-wheel vessels (25.0% vs. 5.0%, p = 0.003), branched vessels (22.9% vs. 5.0%, p = 0.006), blue and pink ingredients >2/3 (85.4% vs. 10.0%, p < 0.001) were more observed in benign FLLs. A nomogram incorporating peripheral nodular, spoke-wheel vessels, and red ingredients >1/3 was constructed. The model had satisfactory discrimination (AUC = 0.937), and the optimal diagnostic threshold value was 0.740 (0.983, 0.850). By the DCA, the model offered a net benefit over the treat-all-patients scheme or the treat-none scheme at a threshold probability 5%-93%.

Using CPI can detect and render subtle information of the main features of FLLs on CEUS; it is conducive to the radiologist for imaging interpretation, and a combining read of the CEUS and CPI of the FLLs with features of "homogenous hyperenhancement and no washout" can improve significantly the diagnostic performance of CEUS for FLLs.

The diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis relies on non-invasive criteria based on international guidelines. The advent of systemic therapies warrants reconsideration of the role of biopsy specimens in the diagnosis of HCC. Accordingly, we investigated the diagnostic performance of the LI-RADS 2018 and the AASLD 2011 criteria.

Consecutive patients with cirrhosis who underwent a biopsy for suspected HCC between 2015 and 2020 were included. The available imaging studies (computed tomography and/or magnetic resonance imaging) were blindly reviewed by two independent radiologists. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed for LI-RADS, AASLD, and biopsies.

In total, 167 patients underwent both available biopsy and imaging. Of the 137 relevant biopsies, 114 patients had HCC (83.2%), 12 (9%) had non-HCC malignant lesions, and 11 (8%) had benign nodules. The PPV and NPV of the biopsies were 100% and 62%, respectively; 30 biopsies were non-contributive. The PPV and NPV of the LI-RADS categories were 89% and 32.8% for LR-5 and 85.5% and 54.5% for LR-4 + 5 + TIV, respectively. The PPV and NPV of the 2011 AASLD criteria were 93.2% and 35.6%, respectively. The interobserver kappa (k = 0.380) for the LR-5 categories was reasonable. Of 100 LR-5 nodules, 11 were misclassified, in particular one case was a colorectal metastasis, and two cases were cholangiocarcinomas, of which nine were identified through biopsy, whereas six were correctly classified according to LI-RADS (LR-M or LR-TIV). Fifty percent of macrotrabecular HCC and 48.4% of poorly differentiated HCC (Edmonson 3 and 4) were not classified as LR-5.

LI-RADS 2018 did not outperform the AASLD 2011 score as a non-invasive diagnosis of HCC. Tumor biopsy allowed restoration of an accurate diagnosis in 11% of LR-5 cases. A combined radiological and histological diagnosis should be considered mandatory for good treatment assessment.

Although biopsy is not required for hepatocellular carcinoma diagnosis when the LI-RADS criteria are met according to current guidelines, our study underscores the limits of radiology and the need for biopsy when hepatocellular carcinoma is suspected. Histological findings could change therapeutics of liver tumors even if only for a small proportion of patients. Histological proof of the type of cancer is a standard in oncology.