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.

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is a significant global health burden. Accurate imaging is crucial for diagnosis and treatment response assessment, often eliminating the need for biopsy. The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation and reporting of liver imaging for diagnosis and treatment response assessment, categorizing observations using defined categories that are based on the probability of malignancy or post-treatment tumor viability. Optimized imaging protocols are essential for accurate visualization and characterization of liver findings by LI-RADS. Common technical pitfalls, such as suboptimal postcontrast phase timing, and MRI-specific challenges like subtraction misregistration artifacts, can significantly reduce image quality and diagnostic accuracy. The use of hepatobiliary contrast agents introduces additional challenges including arterial phase degradation and suboptimal uptake in advanced cirrhosis. This review provides radiologists with comprehensive insights into the technical aspects of liver imaging for LI-RADS. We discuss common pitfalls encountered in routine clinical practice and offer practical solutions to optimize imaging techniques. We also highlight technical advances in liver imaging, including multi-arterial MR acquisition and compressed sensing. By understanding and addressing these technical aspects, radiologists can improve accuracy and confidence in the diagnosis and treatment response assessment for hepatocellular carcinoma.

Background/Objectives: Although immunotherapy is the primary treatment option for intermediate-stage hepatocellular carcinoma (HCC), its efficacy varies. This study aimed to identify non-invasive imaging biomarkers predictive of the immunoscore linked to dynamic contrast-enhanced computed tomography (CECT). Methods: We performed immunohistochemical staining with CD3+ and CD8+ antibodies and counted the positive cells in the invasive margin (IM) and central tumor (CT), converting them to an immunoscore of 0 to 4 points. We assessed the dynamic CECT findings obtained from 96 patients who underwent hepatectomy for HCC and evaluated the relationship between dynamic CECT findings and immunoscores. For validation, we assessed the treatment effects on 81 nodules using the Response Evaluation Criteria in Solid Tumors in another cohort of 41 patients who received combined immunotherapy with atezolizumab and bevacizumab (n = 27) and durvalumab and tremelizumab (n = 14). Results: HCCs with peritumoral enhancement in the arterial phase (p < 0.001) and rim APHE (p = 0.009) were associated with the immunoscore in univariate linear regression analysis and peritumoral enhancement in the arterial phase (p = 0.004) in multivariate linear regression analysis. The time to nodular progression in HCCs with peritumoral enhancement in the arterial phase was significantly longer than that in HCCs without this feature (p < 0.001). Conclusions: We identified HCCs with peritumoral enhancement in the arterial phase as a noninvasive imaging biomarker to predict immune-inflamed HCC with a high immunoscore tendency. These HCCs were most likely to respond to combined immunotherapy.

Atezolizumab plus bevacizumab (Ate/Bev) and lenvatinib (Len) are first-line therapies for unresectable hepatocellular carcinoma (uHCC). However, Ate/Bev's high cost limits its common use in real-life practice, while Len is usually covered by national health insurance (NHI). We conducted this study to compare their effectiveness and safety in real-world settings. We retrospectively evaluated 346 uHCC patients treated with first-line Ate/Bev (n=80) or Len (n=266) from December 2019 to December 2022, using 1:2 ratio propensity score matching (PSM) analyses. Compared to the Len group, the Ate/Bev group exhibited higher incidences of Child-Pugh class B (14.1% vs. 5.7%, P=0.014), larger main tumors (58.8% vs. 40.2%, P=0.003), and more main portal vein invasion (25% vs. 12.8%, P=0.008). Treatment-related adverse events were notably lower in the Ate/Bev group (56.3% vs. 72.3%, P=0.007). After PSM, no significant differences were observed in the objective response rate (21.9% vs. 21.6%, P=0.983), progression-free survival (5.1 vs. 6 months, P=0.783), and overall survival (13.3 vs. 14.1 months, P=0.945) between the Ate/Bev (n=73) and Len (n=142) groups. Patients in the Ate/Bev group received more sequential post-treatments compared to the Len group (45.2% vs. 24.6%, P=0.009). Len-based therapies (n=28, 84.8%) and mono- or combined-immunotherapy (n=19, 54.3%) were the most frequently administered sequential therapies following Ate/Bev and Len, respectively. Patients with uHCC who received first-line self-paid Ate/Bev seemed to have lower liver function reserve and more advanced tumor characteristics compared to those who underwent NHI-reimbursed Len. However, the treatment outcomes and safety profiles were similar between these two groups.

Canine hepatocellular carcinoma (HCC) is characterized by distinct computed tomography (CT) findings. HCC exhibits tumor heterogeneity, with different genomic information and histopathological features within the same tumor. In human HCC, genetic alterations affect the prognosis and treatment, and research has begun to assess genetic alterations using minimally invasive and reproducible CT. However, the relationship between CT findings and the genomic information of canine HCC is unknown. Early contrast of HCC indicates increased intratumoral neovascular growth. In this study, we aimed to investigate the relationship between enhancement patterns in the arterial phase of CT imaging and gene expression in canine HCC using RNA sequencing. Based on the CT findings, three of the eight dogs studied were classified as having enhancement HCC and five as having non-enhancement HCC. RNA sequencing was performed using the mRNA extracted from the specimens. Eight differentially expressed genes met the cutoff criteria. Among these, DUSP9, SLPI, and ALDH1L2 were the most upregulated genes in enhancement HCC, whereas SLC1A1 was the most downregulated in non-enhancement HCC. Canine HCC may involve different angiogenesis mechanisms. CT findings can be used to assess the gene expression status in canine HCC and may add new value to CT imaging.

Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. Multiphasic computed tomography or MRI is the standard for HCC diagnosis, but histological confirmation should be considered, especially when inconclusive findings are seen on cross-sectional imaging. Staging and treatment decisions are complex and should be made in multidisciplinary settings, incorporating multiple factors including tumor burden, degree of liver dysfunction, patient performance status, available expertise, and patient preferences. Early-stage HCC is best treated with curative options such as resection, ablation, or transplantation. For intermediate-stage disease, locoregional therapies are primarily recommended although systemic therapies may be preferred for patients with large intrahepatic tumor burden. In advanced-stage disease, immune checkpoint inhibitor-based therapy is the preferred treatment regimen. In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.

This study aimed to investigate how dynamic contrast-enhanced CT imaging signs correlate with the differentiation grade and microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to assess their predictive value for MVI when combined with clinical characteristics.

We conducted a retrospective analysis of clinical data from 232 patients diagnosed with HCC at our hospital between 2021 and 2022. All patients underwent preoperative enhanced CT scans, laboratory tests, and postoperative pathological examinations. Among the 232 patients, 89 were identified as MVI-positive and 143 as MVI-negative. Regarding tumor differentiation, 56 patients were well-differentiated, 145 moderately, and 31 poorly. Multivariate logistic regression analysis was employed to establish a prediction model for variables showing significant differences. Additionally, the diagnostic performance of various indicators were evaluated using ROC analysis.

Among the qualitative data, significant differences (P<0.05) were observed between the MVI-positive and MVI-negative groups in 5 items such as peritumoral enhancement. In terms of quantitative data, the MVI-positive group exhibited higher maximum tumor length, AST, ALT, AFP levels and the ALBI score (P<0.05). Conversely, CT values in the arterial phase (AP), portal venous phase (PVP), and PT levels were lower in the MVI-positive group (P<0.05). Multivariate Logistic regression analysis identified ALBI score, PT level, CT value in PVP, and tumor capsule as independent risk factors for MVI occurrence (AUC: 0.71, 0.58, 0.66, and 0.60). The combined diagnostic AUC value was 0.82 (95% CI: 0.76-0.87). Significant differences were found among different differentiation grade groups in 10 items such as non-smooth tumor margin (P<0.05).

Preoperative dynamic contrast-enhanced CT examination in patients with HCC can be utilized to predict the presence of MVI. When combined with clinical characteristics, these imaging signs demonstrate good predictive performance for MVI status. Furthermore, this approach has significant implications for determining the differentiation grade of tumors.

The liver is supplied by a dual blood flow system consisting of the portal vein and hepatic artery. Imaging techniques for diagnosing hepatocellular carcinoma (HCC) have been developed along with blood flow imaging, which visualizes the amount of arterial and portal blood flow. The diagnosis of HCC differentiation is important for early-stage liver cancer screening and determination of treatment strategies. Dynamic computed tomography/magnetic resonance imaging (MRI) includes blood flow imaging and MRI with contrast-enhanced ultrasound and liver-specific contrast agents are used in combination. In addition, unlike the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), which is the standard for determining treatment efficacy for solid tumors in general, tumor necrosis is generally considered a treatment effect in HCC, and the modified RECIST and Liver Cancer Direct Effectiveness Criteria (RECICL) are widely used. Familiarity with the definitions, criteria, and potential challenges of the mRECIST and RECICL is essential for their effective application in clinical practice. This review integrates the latest advancements in systemic treatments and imaging techniques, including the role of LI-RADS and updates on molecular-targeted therapies such as regorafenib, supported by some systematic review and meta-analysis.

Liver cancer, specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related deaths, following pancreatic cancer. The 5-year overall survival rate for HCC remains relatively low. Currently, there are multiple treatment options available for HCC, including systemic drugs, minimally invasive local therapies such as radiofrequency ablation, transarterial chemoembolization (TACE), and arterial radioembolization (TARE), as well as surgical interventions like liver resection or transplantation. However, the effectiveness of drug delivery to the cancerous liver is hindered by pathophysiological changes in the organ. In order to address this challenge, lipid-based nanoparticles (LNPs) have emerged as promising platforms for delivering a diverse range of therapeutic drugs. LNPs offer various structural configurations that enhance their physical stability and enable them to accommodate different types of cargo with varying mechanical properties and degrees of hydrophobicity. In this article, we provide a comprehensive review of the current applications of LNPs in the development of anti-HCC therapies. By examining the existing research, we aim to shed light on the potential future directions and advancements in this field.

This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease.

To evaluate the outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) according to the size of the beads for the treatment of small hepatocellular carcinoma (HCC).

This retrospective study included 212 patients with a single HCC ≤5 cm from five tertiary institutions. One hundred and nine patients were treated with 70-150-µm doxorubicin DEBs (group A), and 103 patients received 100-300-µm doxorubicin DEBs (group B). The initial tumor response (assessed between 3 weeks and 2 months after DEB-TACE), time to local tumor progression (TTLTP), restricted mean duration of complete response (RMDCR), rate of complications, incidence of post-embolization syndrome, and length of hospital stay were compared between the two groups. Logistic regression was used to analyze prognostic factors for initial tumor response.

The initial objective response rates were 91.7% (100/109) and 84.5% (87/103) for groups A and B, respectively (P = 0.101). In the subgroup analysis of tumors ≤3 cm, the initial objective response rates were 94.6% (53/56) and 78.0% (39/50) for groups A and B, respectively (P = 0.012). There was no significant difference in the TTLTP (median, 23.7 months for group A vs. 19.0 months for group B; P = 0.278 [log-rank], 0.190 [multivariable Cox regression]) or RMDCR at 24 months (11.4 months vs. 8.5 months, respectively; P = 0.088). In the subgroup analysis of tumors >3-cm, the RMDCR at 24 months was significantly longer in group A than in group B (11.8 months vs. 5.7 months, P = 0.024). The incidence of mild bile duct dilatation after DEB-TACE was significantly higher in group B than in group A (5.5% [6/109] vs. 18.4% [19/103], P = 0.003).

DEB-TACE using 70-150-µm microspheres demonstrated a higher initial objective response rate in ≤3-cm HCCs and a longer RMDCR at 24 months in 3.1-5-cm HCCs compared to larger DEBs (100-300-µm).

Owing to advances in diagnosis and treatment methods over past decades, a growing number of early-stage hepatocellular carcinoma (HCC) diagnoses has enabled a greater of proportion of patients to receive curative treatment. However, a high risk of early recurrence and poor prognosis remain major challenges in HCC therapy. Microvascular invasion (MVI) has been demonstrated to be an essential independent predictor of early recurrence after curative therapy. Currently, biopsy is not generally recommended before treatment to evaluate MVI in HCC according clinical guidelines due to sampling error and the high risk of tumor cell seeding following biopsy. Therefore, the postoperative histopathological examination is recognized as the gold standard of MVI diagnosis, but this lagging indicator greatly impedes clinicians in selecting the optimal effective treatment for prognosis. As imaging can now noninvasively and completely assess the whole tumor and host situation, it is playing an increasingly important role in the preoperative assessment of MVI. Therefore, imaging criteria for MVI diagnosis would be highly desirable for optimizing individualized therapeutic decision-making and achieving a better prognosis. In this review, we summarize the emerging image characteristics of different imaging modalities for predicting MVI. We also discuss whether advances in imaging technique have generated evidence that could be practice-changing and whether advanced imaging techniques will revolutionize therapeutic decision-making of early-stage HCC.

Identification of drainage vessels is useful for differential diagnosis of hepatic tumors. Direct drainage to the hepatic vein has been reported to occur in focal nodular hyperplasia (FNH), but studies evaluating the drainage veins of FNH are limited. We aimed to investigate the detection rate of the FNH drainage vein and the factors related to visualization of the drainage vein on contrast-enhanced ultrasound (CEUS).

Fifty consecutive patients with 50 FNH lesions were retrospectively evaluated in this study. We calculated and compared the detection rate of the FNH drainage vein on CEUS, contrast-enhanced magnetic resonance imaging (CEMRI), and contrast-enhanced computed tomography (CECT), and identified the factors correlated with visualization of the FNH drainage vein on CEUS by using multivariate logistic regression analyses.

Visualization of the drainage vein was confirmed in 31 of 50 lesions (62%) using CEUS, three of 44 lesions (6.8%) using CEMRI, and one of 18 lesions (5.6%) using CECT. The detection rate of the FNH drainage vein on CEUS was significantly higher than that on CEMRI and CECT (p < 0.001). Multivariate analysis identified lesion size (≥ 25 mm) and detection of the spoke-wheel pattern on Doppler US as independent factors for drainage vein detection in FNH.

Our study showed that rapid FNH drainage to the hepatic vein was observed at a relatively high rate on CEUS, suggesting that CEUS focusing on detection of drainage veins is important for diagnosing FNH.

To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI.

A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated.

Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712).

The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.

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.

Due to the trend towards increased use of imaging and rising awareness among high-risk patients, gastroenterologists and hepatologists are more frequently confronted with patients with focal liver lesions. In the differentiation of these lesions, CT and MRI have increasingly found their way into primary diagnostic steps in everyday clinical practice. Contrast-enhanced sonography, on the other hand, is a very effective and cost-efficient method for assessing focal liver lesions. The success of the method is not only based on the visualisation of microvascularisation in real time. If sonography is performed by the treating physician, he can use the exact knowledge of history and clinical findings to specifically adapt the examination procedure and to interpret the sonographic findings with greater accuracy ("clinical sonography"). At the same time, the method enables the practitioner to combine diagnostics and management decisions in his or her own hands. To achieve excellent results with contrast-enhanced sonography-as with any other imaging method-it is necessary that the examiner is sufficiently qualified.This article systematically presents the sonographic characteristics of the most common liver lesions and clearly shows their contrast patterns using videos (available via QR code). The article illustrates that CEUS could-and from the authors' point of view, should-have an even greater significance in the future.

The Liver Imaging Reporting and Data System (LI-RADS) combines standardized terminology with a classification system for imaging findings in patients with HCC, therefore rendering diagnostic biopsy unnecessary in many cases. This retrospective study included 23 patients with a biopsy diagnosis of HCC, performed either before or after local interventional procedures, in order to evaluate the histopathologic changes induced by previous procedures and their potential influence on the response to immune therapy.

The study encompassed a cohort of patients diagnosed with Hepatocellular Carcinoma (HCC). Diagnosis was established via contrast-enhanced computer tomography or magnetic resonance imaging that identified LI-RADS-5 nodules in conjunction with historical liver disease and elevated alpha-fetoprotein (AFP) levels or via histological examination confirming positivity for glypican3, heat shock protein 70, and glutamine synthetase. The study detailed the liver disease etiology, LI-RADS scores, characteristics and dimensions of HCC nodules, serum AFP concentrations, Edmondson-Steiner grading, and the expression of programmed cell death ligand 1 (PD-L1) in the tumor cells.

Among the study's cohort of Hepatocellular Carcinoma (HCC) patients, a portion had not received any prior treatments, while the remainder experienced local HCC recurrence following trans-arterial chemoembolization or radiofrequency ablation. Observations indicated elevated alpha-fetoprotein (AFP) levels in those who had not undergone any previous interventions, showing statistical significance. The Edmondson-Steiner classification predominantly identified grade III differentiation across patients, irrespective of their treatment history. Furthermore, an increase in intra-tumoral programmed cell death ligand 1 (PD-L1) expression was noted in patients who had not been subjected to previous therapies.

Liver biopsy offers valuable insights for patients with Hepatocellular Carcinoma (HCC), assisting in the tailoring of immune therapy strategies, particularly in cases of recurrence following prior local interventions.

Based on enhanced MRI, a prediction model of microvascular invasion (MVI) for hepatocellular carcinoma (HCC) was developed using graph convolutional network (GCN) combined nomogram.

We retrospectively collected 182 HCC patients confirmed histopathologically, all of them performed enhanced MRI before surgery. The patients were randomly divided into training and validation groups. Radiomics features were extracted from the arterial phase (AP), portal venous phase (PVP), and delayed phase (DP), respectively. After removing redundant features, the graph structure by constructing the distance matrix with the feature matrix was built. Screening the superior phases and acquired GCN Score (GS). Finally, combining clinical, radiological and GS established the predicting nomogram.

27.5% (50/182) patients were with MVI positive. In radiological analysis, intratumoural artery (P = 0.007) was an independent predictor of MVI. GCN model with grey-level cooccurrence matrix-grey-level run length matrix features exhibited area under the curves of the training group was 0.532, 0.690, and 0.885 and the validation group was 0.583, 0.580, and 0.854 for AP, PVP, and DP, respectively. DP was selected to develop final model and got GS. Combining GS with diameter, corona enhancement, mosaic architecture, and intratumoural artery constructed a nomogram which showed a C-index of 0.884 (95% CI: 0.829-0.927).

The GCN model based on DP has a high predictive ability. A nomogram combining GS, clinical and radiological characteristics can be a simple and effective guiding tool for selecting HCC treatment options.

GCN based on MRI could predict MVI on HCC.

To elucidate how precisely microvascular invasion (MVI) in hepatocellular carcinoma (HCC) can be predicted using multiparametric assessment of gadoxetic acid-enhanced MRI.

In this retrospective single-center study, patients who underwent liver resection or transplantation of HCC were evaluated. Data obtained in patients who underwent liver resection were used as the training set. Nine kinds of MR findings for predicting MVI were compared between HCCs with and without MVI by univariate analysis, followed by multiple logistic regression analysis. Using significant findings, a predictive formula for diagnosing MVI was obtained. The diagnostic performance of the formula was investigated in patients who underwent liver resection (validation set 1) and in patients who underwent liver transplantation (validation set 2) using a receiver operating characteristic curve analysis. The area under the curves (AUCs) of these three groups were compared.

A total of 345 patients with 356 HCCs were selected for analysis. Tumor diameter (D) (P = 0.021), tumor washout (TW) (P < 0.01), and peritumoral hypointensity in the hepatobiliary phase (PHH) (P < 0.01) were significantly associated with MVI after multivariate analysis. The AUCs for predicting MVI of the predictive formula were as follows: training set, 0.88 (95% confidence interval (CI) 0.82,0.93); validation set 1, 0.81 (95% CI 0.73,0.87); validation set 2, 0.67 (95% CI 0.51,0.80). The AUCs were not significantly different among three groups (training set vs validation set 1; P = 0.15, training set vs validation set 2; P = 0.09, validation set 1 vs validation set 2; P = 0.29, respectively).

Our multiparametric assessment of gadoxetic acid-enhanced MRI performed quite precisely and with good reproducibility for predicting MVI.

Neoangiogenesis plays a crucial role in the progression of hepatocellular carcinoma (HCC), and concerns have been raised about the role of neoangiogenesis on the effectiveness of transarterial chemoembolization (TACE).

In this study, we aimed to evaluate Vascular Endothelial Growth Factor (VEGF) and Hypoxia-Inducible Factor-1α (HIF-1α) as circulating prognostic biomarkers in HCC patients treated with TACE.

Blood samples were collected from 163 patients before (t0) and four weeks after TACE (t1).

Higher levels of VEGF after TACE were demonstrated (264.0 [78.7-450.8] vs. 278.6 [95.0-576.6] pg/mL; p < 0.0001). Responders to TACE had lower levels of VEGF than non-responders both at t0 (200.0 [58.9-415.8] vs. 406.6 [181.4-558.6] pg/mL; p = 0.006) and at t1 (257.3 [68.5-528.6] vs. 425.9 [245.2-808.3] pg/mL; p = 0.003), and in both groups there was an increase in VEGF compared to measurements before treatment (p = 0.001 and p = 0.005, respectively). VEGF was not associated with overall survival (OS), while patients with HIF-1α ≤ 0.49 ng/mL showed better prognosis (median OS 28.0 months [95% CI 19.7-36.3] vs. 17.0 months [95% CI 11.1-22.9]; p = 0.01). Moreover, HIF-1α was identified as an independent prognostic parameter.

VEGF and HIF-1α can be considered useful prognostic biomarkers in HCC patients treated with TACE.

Microvascular invasion (MVI) is a significant prognostic factor in combined hepatocellular cholangiocarcinoma (cHCC-CCA). However, its diagnosis relies on postoperative histopathologic analysis. This study aims to identify preoperative inflammatory biomarkers and MR-imaging features that can predict MVI in cHCC-CCA.

This retrospective study enrolled 119 patients with histopathologically confirmed cHCC-CCA between January 2016 and December 2021. Two radiologists, unaware of the clinical data, independently reviewed all MR image features. Univariable and multivariable analyses were performed to determine the independent predictors for MVI among inflammatory biomarkers and MRI characteristics. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic performance.

Multivariable logistic regression analysis identified four variables significantly associated with MVI (p < 0.05), including two inflammatory biomarkers [albumin-to-alkaline phosphatase ratio (AAPR) and aspartate aminotransferase-to-neutrophil ratio index (ANRI)] and two MRI features (non-smooth tumor margin and arterial phase peritumoral enhancement). A combined model for predicting MVI was constructed based on these four variables, with an AUC of 0.802 (95% CI 0.719-0.870). The diagnostic efficiency of the combined model was higher than that of the imaging model.

Inflammatory biomarkers and MRI features could be potential predictors for MVI in cHCC-CCA. The combined model, derived from inflammatory biomarkers and MRI features, showed good performance in preoperatively predicting MVI in cHCC-CCA patients.

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.

To estimate the potential of preoperative MRI features in the prediction of the integration patterns of vessels that encapsulate tumor clusters (VETC) and microvascular invasion (MVI) (VM) patterns in hepatocellular carcinoma (HCC) patients after resection and to assess the prognostic value of VM patterns.

Patients who underwent surgical resection for HCC between July 2019 and July 2020 were retrospectively included in the training cohort and validation cohort. In the training cohort, patients were classified into VM-positive HCC (VM-HCC) and VM-negative HCC (non-VM HCC). Predictors associated with VM-HCC were determined by using logistic regression analyses and used to build a prediction model of VM-HCC. The model was tested in the validation cohort by area under the receiver operating characteristic curve (AUC) analysis. Prognostic factors associated with early recurrence of HCC were evaluated by use of Cox logistic regression analyses.

Alpha-fetoprotein (AFP) level higher than 400 ng/mL (odds ratio [OR] = 8.0; 95% CI: 2.6-25.2; P < 0.001), non-smooth tumor margin (OR = 3.1; 95% CI: 1.4-6.0; P < 0.001) and peritumoral arterial enhancement (OR = 2.9; 95% CI: 1.4-6.2; P = 0.004) were independent predictors of VM-HCC. The AUCs of the prediction model for VM-HCC were 0.81 for the training cohort and 0.79 for the validation cohort. The high risk of VM-HCC predicted by the three preoperative predictors derived from the prediction model (hazard ratio [HR] 2.0; 95% CI: 1.3, 3.2; P = 0.003) were independently associated with early recurrence, while pathologically confirmed VM-HCC (HR 2.8; 95% CI: 1.6, 3.8; P < 0.001) and satellite nodules (HR 1.8; 95% CI: 1.1, 3.1; P = 0.025) were independently associated with early recurrence after surgical resection.

The predictive model can be used to predict VM patterns. VM-HCC is associated with increased risk of early recurrence after surgical resection in HCC.

Medical image analysis plays a pivotal role in the evaluation of diseases, including screening, surveillance, diagnosis, and prognosis. Liver is one of the major organs responsible for key functions of metabolism, protein and hormone synthesis, detoxification, and waste excretion. Patients with advanced liver disease and Hepatocellular Carcinoma (HCC) are often asymptomatic in the early stages; however delays in diagnosis and treatment can lead to increased rates of decompensated liver diseases, late-stage HCC, morbidity and mortality. Ultrasound (US) is commonly used imaging modality for diagnosis of chronic liver diseases that includes fibrosis, cirrhosis and portal hypertension. In this paper, we first provide an overview of various diagnostic methods for stages of liver diseases and discuss the role of Computer-Aided Diagnosis (CAD) systems in diagnosing liver diseases. Second, we review the utility of machine learning and deep learning approaches as diagnostic tools. Finally, we present the limitations of existing studies and outline future directions to further improve diagnostic accuracy, as well as reduce cost and subjectivity, while also improving workflow for the clinicians.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The hypervascular nature of the majority of HCCs and the peculiar vascular derangement occurring during liver carcinogenesis underscore the importance of angiogenesis in the development and progression of these tumors. Indeed, several angiogenic molecular pathways have been identified as deregulated in HCC. The hypervascular nature and the peculiar vascularization of HCC, as well as deregulated angiogenic pathways, represent major therapeutic targets. To a large extent, intra-arterial locoregional treatments (transarterial-(chemo)embolization) rely on tumor ischemia caused by embolization of tumor feeding arteries, even though this may represent the "primum movens" of tumor recurrence through the activation of neoangiogenesis. Considering systemic therapies, the currently available tyrosine kinase inhibitors (sorafenib, regorafenib, cabozantinib and lenvatinib) and monoclonal antibodies (ramucirumab and bevacizumab, in combination with the anti-PD-L1, atezolizumab) primarily target, among others, angiogenic pathways. Considering the importance of angiogenesis in the pathogenesis and treatment of liver cancer, in this paper, we aim to review the role of angiogenesis in HCC, addressing the molecular mechanisms, available antiangiogenic therapies and prognostic biomarkers in patients receiving these treatments.

We describe the clinical effects of short-term lenvatinib administration prior to conventional transarterial chemoembolization (cTACE) on tumor vasculature. Two patients with unresectable hepatocellular carcinoma underwent high-resolution digital subtraction angiography (DSA) and perfusion four-dimensional computed tomography during hepatic arteriography (4D-CTHA) before and after administration of lenvatinib treatment. The doses and periods of lenvatinib administration were, respectively, 12 mg/day for 7 days and 8 mg/day for 4 days. In both cases, high-resolution DSA revealed a decrease in dilatation and tortuosity of the tumor vessels. Furthermore, the tumor staining became more refined, and newly formed tiny tumor vessels were observed. Perfusion 4D-CTHA revealed a decrease in arterial blood flow to the tumor by 28.6% (from 487.9 to 139.5 mL/min/100 mg) and 42.5% (from 288.2 to 122.6 mL/min/100 mg) in the two cases, respectively. The cTACE procedure resulted in good lipiodol accumulation and complete response. Patients have remained recurrence-free for 12 and 11 months after the cTACE procedure, respectively. The administration of short-term lenvatinib in these two cases resulted in the normalization of tumor vessels, which likely led to improved lipiodol accumulation and a favorable antitumor effect.

Contrast-enhanced medical imaging is commonly requested in clinical practice. Contrast media provide better differentiation of tissue enhancement, improves the soft tissue contrast resolution, and enhances the ability to study the physiology and function of the organs and/or systems. However, contrast media may cause complications, especially in patients with renal failure. This article discusses the use of contrast media in common imaging modalities and the relationship between contrast media and renal function. Administration of iodinated contrast media in computed tomography may cause contrast-associated acute kidney injury; the risk factors and preventive strategies for this are elaborated in this article. Administration of gadolinium-based contrast media in magnetic resonance imaging may lead to nephrogenic systemic fibrosis. Therefore, precautions should be taken when planning for medical imaging for patients with pre-existing acute kidney injury or end-stage chronic kidney disease, for whom contrast media administration in computed tomography or magnetic resonance imaging may be relatively contraindicated. Alternatively, ultrasound contrast agents can be safely used in patients with acute kidney injury or chronic kidney disease. Clinical teams should discuss these patients with radiologists, taking into account the risk-benefits of contrast media, to determine the optimal imaging protocol or modality to answer the clinical query.

Microvascular invasion (MVI) is significantly associated with prognosis in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients. The study aimed to explore the value of preoperative contrast-enhanced CT (CECT) features and clinical data in predicting MVI of cHCC-CCA.

A total of 33 patients with MVI-positive and 27 with MVI-negative were enrolled, and underwent preoperative CECT imaging from January 2016 to December 2021. Preoperative clinical data and CECT imaging features were retrospectively analyzed. Univariable and multivariable logistic regression analysis were performed to identify potential predictors of MVI in cHCC-CCA. The diagnostic performance was evaluated by the receiver operating characteristic (ROC) curve and its area under the curve (AUC) value.

The mean age of the patients was 54.0 ± 10.3 years, and 53 of the 60 patients (88.3%) were male. Preoperative imaging features on CECT (non-smooth contour and arterial phase peritumoral enhancement) and clinical data (hepatitis B virus (HBV) infection and protein induced by vitamin K absence or antagonist-II (PIVKA-II)) were highly distinct between those in MVI-positive group and MVI-negative group. On multivariable logistic analysis, arterial phase peritumoral enhancement (odds ratio (OR), 6.514; 95% confidence interval (CI), 1.588-26.728, p = 0.012) and high serum PIVKA-II level (OR, 6.810; 95% CI, 1.796-25.820, p = 0.005) were independent predictors associated with MVI of cHCC-CCA. The combination of these two predictors had high sensitivity (31/33, 93.9%; 95% CI, 80.4% - 98.3%) in the prediction of MVI with an area under the receiver operating characteristic (ROC) curve of 0.763 (95% CI, 0.635-0.863).

The findings indicated that arterial phase peritumoral enhancement on preoperative CECT and high serum PIVKA-II level were identified as potential predictors for MVI in cHCC-CCA patients.

The cross-sectional imaging findings play a crucial role in the diagnosis of hepatocellular carcinoma (HCC). Recent studies have shown that imaging findings of HCC are not only relevant for the diagnosis of HCC, but also for identifying genetic and pathologic characteristics and determining prognosis. Imaging findings such as rim arterial phase hyperenhancement, arterial phase peritumoral hyperenhancement, hepatobiliary phase peritumoral hypointensity, non-smooth tumor margin, low apparent diffusion coefficient, and the LR-M category of the Liver Imaging-Reporting and Data System have been reported to be associated with poor prognosis. In contrast, imaging findings such as enhancing capsule appearance, hepatobiliary phase hyperintensity, and fat in mass have been reported to be associated with a favorable prognosis. Most of these imaging findings were examined in retrospective, single-center studies that were not adequately validated. However, the imaging findings can be applied for deciding the treatment strategy for HCC, if their significance can be confirmed by a large multicenter study. In this literature, we would like to review imaging findings related to the prognosis of HCC as well as their associated clinicopathological characteristics.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide and it ranges from simple steatosis to hepatocellular carcinoma (HCC). HCC represents the first liver tumor and the third source of cancer death. In the next few years, the prevalence of NAFLD and consequently of HCC is estimated to increase, becoming a major public health problem. The NAFLD-HCC shows several differences compared to other causes of chronic liver disease (CLD), including the higher percentage of patients that develop HCC in the absence of liver cirrhosis. In HCC surveillance, the international guidelines suggest a six months abdominal ultrasound (US), with or without alpha-fetoprotein (AFP) evaluation, in patients with cirrhosis and in a subgroup of patients with chronic hepatitis B infection. However, this screening program reveals several limitations, especially in NAFLD patients. Thus, new biomarkers and scores have been proposed to overcome the limits of HCC surveillance. In this narrative review we aimed to explore the differences in the HCC features between NAFLD and non-NAFLD patients, and those between NAFLD-HCC developed in the cirrhotic and non-cirrhotic liver. Finally, we focused on the limits of tumor surveillance in NAFLD patients, and we explored the new biomarkers for the early diagnosis of HCC.

Glypican-3 (GPC-3) is a heparan sulfate proteoglycan overexpressed by hepatocellular carcinoma (HCC) cells. Several studies highlighted the diagnostic and prognostic value of GPC-3 expression in liver tissue, while data on the reliability of serum GPC-3 are limited and conflicting. We aimed to evaluate the prognostic value of serum GPC-3 in patients with HCC.

A total of 449 patients (91 F and 358 M; median age 65 [38-86] years) with a new diagnosis of HCC and available serum samples collected at tumor diagnosis were retrospectively analyzed. All patients had cirrhosis and the main underlying etiology was viral (N.=323, 72%). Barcelona Clinic Liver Cancer (BCLC) staging system was adopted for patients' classification (BCLC 0/A, N.=293, 65% vs. B/C/D, N.=156, 35%) and treatment allocation. Response to therapy was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST).

Median overall survival (OS) after HCC diagnosis was 30 months (95% confidence interval [CI]: 27-34). Patients with serum GPC-3>150 pg/mL showed lower overall survival (16; 95%CI: 13-24 months) compared to those with GPC-3≤150 pg/mL (36; 95%CI: 30-56 months) (Log-rank test, P<0.001). At multivariate Cox proportional-hazard regression analysis, presence of ascites (adjusted Hazard Ratio [aHR]=1.84; 95%CI: 1.23-2.74, P=0.003), BCLC stage (aHR=1.65; 95%CI: 1.39-1.97, P<0.001), mRECIST (aHR=0.33; 95%CI: 0.21-0.51, P<0.001) and GPC-3>150 pg/mL (aHR=2.02; 95%CI: 1.47-2.78, P<0.001) resulted significantly associated to overall survival.

Serum GPC-3 resulted an independent prognostic factor for patients with HCC irrespectively from tumor stage and response to therapy.

To establish a model for assessing the overall survival (OS) of the hepatocellular carcinoma (HCC) patients after hepatectomy based on the clinical and radiomics features.

This study recruited a total of 267 patients with HCC, which were randomly divided into the training (N = 188) and validation (N = 79) cohorts. In the training cohort, radiomic features were selected with the intra-reader and inter-reader correlation coefficient (ICC), Spearman's correlation coefficient, and the least absolute shrinkage and selection operator (LASSO). The radiomics signatures were built by COX regression analysis and compared the predictive potential in the different phases (arterial, portal, and double-phase) and regions of interest (tumor, peritumor 3 mm, peritumor 5 mm). A clinical-radiomics model (CR model) was established by combining the radiomics signatures and clinical risk factors. The validation cohort was used to validate the proposed models.

A total of 267 patients 86 (45.74%) and 37 (46.84%) patients died in the training and validation cohorts, respectively. Among all the radiomics signatures, those based on the tumor and peritumor (5 mm) (AP-TP5-Signature) showed the best prognostic potential (training cohort 1-3 years AUC:0.774-0.837; validation cohort 1-3 years AUC:0.754-0.810). The CR model showed better discrimination, calibration, and clinical applicability as compared to the clinical model and radiomics features. In addition, the CR model could perform risk-stratification and also allowed for significant discrimination between the Kaplan-Meier curves in most of the subgroups.

The CR model could predict the OS of the HCC patients after hepatectomy.

The routine use of dynamic-contrast-enhanced MRI (DCE-MRI) of the liver using hepatocyte-specific contrast agent (HSCA) as the standard of care for the study of focal liver lesions is not widely accepted and opponents invoke the risk of a loss in near 100% specificity of extracellular contrast agents (ECA) and the need for prospective head-to-head comparative studies evaluating the diagnostic performance of both contrast agents. The Purpose of this prospective intraindividual study was to conduct a quantitative and qualitative head-to-head comparison of DCE-MRI using HSCA and ECA in patients with liver cirrhosis and HCC. Twenty-three patients with liver cirrhosis and proven HCC underwent two 3 T-MR examinations, one with ECA (gadoteric acid) and the other with HSCA (gadoxetic acid). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), wash-in, wash-out, image quality, artifacts, lesion conspicuity, and major imaging features of LI-RADS v2018 were evaluated. Wash-in and wash-out were significantly stronger with ECA compared to HSCA (P < 0.001 and 0.006, respectively). During the late arterial phase (LAP), CNR was significantly lower with ECA (P = 0.005), while SNR did not differ significantly (P = 0.39). In qualitative analysis, ECA produced a better overall image quality during the portal venous phase (PVP) and delayed phase (DP) compared to HSCA (P = 0.041 and 0.008), showed less artifacts in the LAP and PVP (P = 0.003 and 0.034) and a higher lesion conspicuity in the LAP and PVP (P = 0.004 and 0.037). There was no significant difference in overall image quality during the LAP (P = 1), in artifacts and lesion conspicuity during the DP (P = 0.078 and 0.073) or in the frequency of the three major LI-RADS v2018 imaging features. In conclusion, ECA provides superior contrast of HCC-especially hypervascular HCC lesions-in DCE-MR in terms of better perceptibility of early enhancement and a stronger washout.

Hepatocellular carcinoma (HCC) is a common malignancy threatening human health, and existing diagnostic and therapeutic techniques are facing great challenges. In the last decade or so, nanotechnology has been developed and improved for tumor diagnosis and treatment. For example, nano-intravenous injections have been approved for malignant perivascular epithelioid cell tumors. This article provides a comprehensive review of the applications of nanotechnology in HCC in recent years: (I) in radiological imaging, magnetic resonance imaging (MRI), fluorescence imaging (FMI) and multimodality imaging. (II) For diagnostic applications in HCC serum markers. (III) As embolic agents in transarterial chemoembolization (TACE) or directly as therapeutic drugs. (IV) For application in photothermal therapy and photodynamic therapy. (V) As carriers of chemotherapeutic drugs, targeted drugs, and natural plant drugs. (VI) For application in gene and immunotherapy. Compared with the traditional methods for diagnosis and treatment of HCC, nanoparticles have high sensitivity, reduce drug toxicity and have a long duration of action, and can also be combined with photothermal and photodynamic multimodal combination therapy. These summaries provide insights for the further development of nanotechnology applications in HCC.

Vascular embolization is a non-surgical procedure used to treat diseases or morbid conditions related to blood vessels, such as bleeding, arteriovenous malformation, aneurysm, and hypervascular tumors, through the intentional occlusion of blood vessels. Among various types of embolic agents that have been applied, liquid embolic agents are gaining an increasing amount of attention owing to their advantages in distal infiltration into regions where solid embolic agents cannot reach, enabling more extensive embolization. Meanwhile, recent advances in biomaterials and technologies have also contributed to the development of novel liquid embolic agents that can resolve the challenges faced while using the existing embolic materials. In this review, we briefly summarize the clinically used embolic agents and their applications, and then present selected research results that overcome the limitations of the embolic agents in use. Through this review, we suggest the required properties of liquid embolic agents that ensure efficacy, which can replace the existing agents, providing directions for the future development in this field.

The 2019 5th edition of the WHO classification of digestive system tumors estimates that up to 35% of hepatocellular carcinomas (HCCs) can be classified as one of eight subtypes defined by molecular characteristics: steatohepatitic, clear cell, macrotrabecular-massive, scirrhous, chromophobe, fibrolamellar, neutrophil-rich, and lymphocyte-rich HCCs. Due to their distinct cellular and architectural characteristics, these subtypes may not display arterial phase hyperenhancement and washout appearance, which are the classic MRI features of HCC, creating challenges in noninvasively diagnosing such lesions as HCC. Moreover, certain subtypes with atypical imaging features have a worse prognosis than other HCCs. A range of distinguishing imaging features may help raise suspicion that a liver lesion represents one of these HCC subtypes. In this review, we describe the MRI features that have been reported in association with various HCC subtypes according to the 2019 WHO classification, with attention given to the current understanding of these subtypes' pathologic and molecular bases and relevance to clinical practice. Imaging findings that differentiate the subtypes from benign liver lesions and non-HCC malignancies are highlighted. Familiarity with these sub-types and their imaging features may allow the radiologist to suggest their presence, though histologic analysis remains needed to establish the diagnosis.