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Objectives: Contrast-enhanced MRI can provide individualized prognostic information for hepatocellular carcinoma (HCC). We aimed to investigate the value of MRI features to predict early (≤ 2 years)/late (> 2 years) recurrence-free survival (E-RFS and L-RFS, respectively) and overall survival (OS)., Materials and Methods: Consecutive adult patients at a tertiary academic center who received curative-intent liver resection for very early to intermediate stage HCC and underwent preoperative contrast-enhanced MRI were retrospectively enrolled from March 2011 to April 2021. Three masked radiologists independently assessed 54 MRI features. Uni- and multivariable Cox regression analyses were conducted to investigate the associations of imaging features with E-RFS, L-RFS, and OS., Results: This study included 600 patients (median age, 53 years; 526 men). During a median follow-up of 55.3 months, 51% of patients experienced recurrence (early recurrence: 66%; late recurrence: 34%), and 17% died. Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing in solid mass, tumor growth pattern, and gastroesophageal varices were associated with E-RFS and OS (largest p = .02). Nonperipheral washout (p = .006), markedly low apparent diffusion coefficient value (p = .02), intratumoral arteries (p = .01), and width of the main portal vein (p = .03) were associated with E-RFS but not with L-RFS or OS, while the VICT2 trait was specifically associated with OS (p = .02). Multiple tumors (p = .048) and radiologically-evident cirrhosis (p < .001) were the only predictors for L-RFS., Conclusion: Twelve visually-assessed MRI features predicted postoperative E-RFS (≤ 2 years), L-RFS (> 2 years), and OS for very early to intermediate-stage HCCs., Clinical Relevance Statement: The prognostic MRI features may help inform personalized surgical planning, neoadjuvant/adjuvant therapies, and postoperative surveillance, thus may be included in future prognostic models., Key Points: • Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing, tumor growth pattern, and gastroesophageal varices predicted both recurrence-free survival within 2 years and overall survival. • Nonperipheral washout, markedly low apparent diffusion coefficient value, intratumoral arteries, and width of the main portal vein specifically predicted recurrence-free survival within 2 years, while the VICT2 trait specifically predicted overall survival. • Multiple tumors and radiologically-evident cirrhosis were the only predictors for recurrence-free survival beyond 2 years., (© 2023. The Author(s).)

Purpose: As a coreceptor in Wnt and HGF signaling, glypican-3 (GPC-3) promotes the progression of tumor and is associated with a poor prognosis in hepatocellular carcinoma (HCC). GPC-3 has evolved as a target molecule in various immunotherapies, including chimeric antigen receptor T cell. However, its evaluation still relies on invasive histopathologic examination. Therefore, we aimed to develop an easy-to-use and noninvasive risk score integrating preoperative gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) and clinical indicators to predict positive GPC-3 expression in HCC., Methods and Materials: Consecutive patients with surgically-confirmed solitary HCC who underwent preoperative EOB-MRI between January 2016 and November 2021 were retrospectively included. EOB-MRI features were independently evaluated by two masked abdominal radiologists and the expression of GPC-3 was determined by two liver pathologists. On the training dataset, a predictive scoring system for GPC-3 was developed against pathology via logistical regression analysis. Model performances were characterized by computing areas under the receiver operating characteristic curve (AUCs)., Results: A total of 278 patients (training set, n=156; internal validation set, n=39; external validation set, n=83) with solitary HCC (208 [75%] with positive GPC-3 expression) were included. Serum alpha-fetoprotein >10 ng/ml (AFP, odds ratio [OR]=2.3, four points) and five EOB-MR imaging features, including tumor size >3.0cm (OR=0.5, -3 points), nonperipheral "washout" (OR=3.0, five points), infiltrative appearance (OR=9.3, 10 points), marked diffusion restriction (OR=3.3, five points), and iron sparing in solid mass (OR=0.2, -7 points) were significantly associated with positive GPC-3 expression. The optimal threshold of scoring system for predicting GPC-3 positive expression was 5.5 points, with AUC 0.726 and 0.681 on the internal and external validation sets, respectively., Conclusion: Based on serum AFP and five EOB-MRI features, we developed an easy-to-use and noninvasive risk score which could accurately predict positive GPC-3 HCC, which may help identify potential responders for GPC-3-targeted immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Qin, Wu, Wei, Wei, Zhang, Duan, Jiang and Song.)

Background: Hepatocellular carcinoma (HCC) expressing cytokeratin (CK) 7 or CK19 has a cholangiocyte phenotype that stimulates HCC proliferation, metastasis, and sorafenib therapy resistance This study aims to noninvasively predict cholangiocyte phenotype-positive HCC and assess its prognosis after hepatectomy. Methods: Between January 2010 and May 2022, preoperative contrast-enhanced MRI was performed on consecutive patients who underwent hepatectomy and had pathologically confirmed solitary HCC. Two abdominal radiologists separately assessed the MRI features. A predictive model for cholangiocyte phenotype HCC was created using logistic regression analysis and five-fold cross-validation. A receiver operating characteristic curve was used to calculate the model performance. Kaplan–Meier and log-rank methods were used to evaluate survival outcomes. Results: In total, 334 patients were included in this retrospective study. Four contrast-enhanced MRI features, including "rim arterial phase hyperenhancement" (OR = 5.9, 95% confidence interval [CI]: 2.9–12.0, 10 points), "nodule in nodule architecture" (OR = 3.5, 95% CI: 2.1–5.9, 7 points), "non-smooth tumor margin" (OR = 1.6, 95% CI: 0.8–2.9, 3 points), and "non-peripheral washout" (OR = 0.6, 95% CI: 0.3–1.0, − 3 points), were assigned to the cholangiocyte phenotype HCC prediction model. The area under the curves for the training and independent validation set were 0.76 and 0.73, respectively. Patients with model-predicted cholangiocyte phenotype HCC demonstrated lower rates of recurrence-free survival (RFS) and overall survival (OS) after hepatectomy, with an estimated median RFS and OS of 926 vs. 1565 days (p < 0.001) and 1504 vs. 2960 days (p < 0.001), respectively. Conclusions: Contrast-enhanced MRI features can be used to predict cholangiocyte phenotype-positive HCC. Patients with pathologically confirmed or MRI model-predicted cholangiocyte phenotype HCC have a worse prognosis after hepatectomy. Critical relevance statement: Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC and a worse prognosis following hepatectomy; these features may assist in predicting prognosis after surgery and improve personalized treatment decision-making. Key points: • Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC. • A noninvasive cholangiocyte phenotype HCC predictive model was established based on MRI features. • Patients with cholangiocyte phenotype HCC demonstrated a worse prognosis following hepatic resection. [ABSTRACT FROM AUTHOR]

Background: The Liver Imaging Reporting and Data System (LI‐RADS) is widely used for diagnosing hepatocellular carcinoma (HCC), however, with unsatisfactory sensitivity, complex ancillary features, and inadequate integration with gadoxetate disodium (EOB)‐enhanced MRI. Purpose: To modify LI‐RADS (mLI‐RADS) on EOB‐MRI. Study Type: Secondary analysis of a prospective observational study. Population: Between July 2015 and September 2018, 224 consecutive high‐risk patients (median age, 51 years; range, 26–83; 180 men; training/testing sets: 169/55 patients) with 742 (median size, 13 mm; interquartile range, 7–27; 498 HCCs) LR‐3/4/5 observations. Field Strength/Sequence: 3.0 T T2‐weighted fast spin‐echo, diffusion‐weighted spin‐echo based echo‐planar, and 3D T1‐weighted gradient echo sequences. Assessment: Three radiologists (with 5, 5, and 10 years of experience in liver MR imaging, respectively) blinded to the reference standard (histopathology or imaging follow‐up) reviewed all MR images independently. In the training set, the optimal LI‐RADS version 2018 (v2018) features selected by Random Forest analysis were used to develop mLI‐RADS via decision tree analysis. Statistical Tests: In an independent testing set, diagnostic performances of mLI‐RADS, LI‐RADS v2018, and the Korean Liver Cancer Association (KLCA) guidelines were computed using a generalized estimating equation model and compared with McNemar's test. A two‐tailed P < 0.05 was statistically significant. Results: Five features (nonperipheral "washout," restricted diffusion, nonrim arterial phase hyperenhancement [APHE], mild–moderate T2 hyperintensity, and transitional phase hypointensity) constituted mLI‐RADS, and mLR‐5 was nonperipheral washout coupled with either nonrim APHE or restricted diffusion. In the testing set, mLI‐RADS was significantly more sensitive (72%) and accurate (80%) than LI‐RADS v2018 (sensitivity, 61%; accuracy 74%; both P < 0.001) and the KLCA guidelines (sensitivity, 64%; accuracy 74%; both P < 0.001), without sacrificing positive predictive value (mLI‐RADS, 94%; LI‐RADS v2018, 94%; KLCA guidelines, 92%). Data Conclusion: In high‐risk patients, the EOB‐MRI‐based mLI‐RADS was simpler and more sensitive for HCC than LI‐RADS v2018 while maintaining high positive predictive value. Level of Evidence: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: The Liver Imaging Reporting and Data System (LI‐RADS) is widely accepted as a reliable diagnostic scheme for hepatocellular carcinoma (HCC) in at‐risk patients. However, its application is hampered by substantial complexity and suboptimal diagnostic sensitivity. Purpose: To propose data‐driven modifications to the LI‐RADS version 2018 (v2018) major feature system (rLI‐RADS) on gadoxetate disodium (EOB)‐enhanced magnetic resonance imaging (MRI) to improve sensitivity and simplicity while maintaining high positive predictive value (PPV) for detecting HCC. Study Type: Retrospective. Population: Two hundred and twenty‐four consecutive at‐risk patients (training dataset: 169, independent testing dataset: 55) with 742 LR‐3 to LR‐5 liver observations (HCC: N = 498 [67%]) were analyzed from a prospective observational registry collected between July 2015 and September 2018. Field Strength/Sequence: 3.0 T/T2‐weighted fast spin‐echo, diffusion‐weighted spin‐echo based echo‐planar and three‐dimensional (3D) T1‐weighted gradient echo sequences. Assessment: All images were evaluated by three independent abdominal radiologists who were blinded to all clinical, pathological, and follow‐up information. Composite reference standards of either histopathology or imaging follow‐up were used. Statistical Tests: In the training dataset, LI‐RADS v2018 major features were used to develop rLI‐RADS based on their associated PPV for HCC. In an independent testing set, diagnostic performances of LI‐RADS v2018 and rLI‐RADS were computed using a generalized estimating equation model and compared with McNemar's test. A P value <0.05 was considered statistically significant. Results: The median (interquartile range) size of liver observations was 13 mm (7–27 mm). The diagnostic table for rLI‐RADS encompassed 9 cells, as opposed to 16 cells for LI‐RADS v2018. In the testing set, compared to LI‐RADS v2018, rLI‐RADS category 5 demonstrated a significantly superior sensitivity (76% vs. 61%) while maintaining comparably high PPV (92.5% vs. 94.1%, P = 0.126). Data Conclusion: Compared with LI‐RADS v2018, rLI‐RADS demonstrated improved simplicity and significantly superior diagnostic sensitivity for HCC in at‐risk patients. Level of Evidence: 3 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

To develop a predictive model integrating clinical and MRI features for postoperative survival in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). Between January 2008 and May 2021, consecutive HCC patients with PVTT who underwent preoperative contrast-enhanced MRI and surgical resection at a tertiary hospital were retrospectively enrolled. The MR images were independently reviewed by two blinded radiologists. Univariate and multivariate Cox regression analyses were performed to construct a prognostic score for overall survival (OS). Ninety-four patients were included (mean age, 50.1 years; 84 men). During a median follow-up period of 15.3 months, 72 (76.6%) patients died (median OS, 15.4 months; median disease-free survival [DFS], 4.6 months). The sum size of the two largest tumors (hazard ratio [HR], 3.050; p < 0.001) and tumor growth subtype (HR, 1.928; p = 0.006) on MRI, serum albumin (HR, 0.948; p = 0.02), and age (HR, 0.978; p = 0.04) were associated with OS and incorporated in the prognostic score. Accordingly, patients were stratified into a high-risk or low-risk group, and the OS in the high-risk group was shorter than that in the low-risk group for the entire cohort (11.7 vs. 25.0 months, p < 0.001) and for patients with Cheng's type I (12.1 vs. 25.9 months, p = 0.002) and type II PVTT (11.7 vs. 25.0 months, p = 0.004). The DFS in the high-risk group was shorter than that in the low-risk group for the entire cohort (4.5 vs. 6.1 months, p = 0.001). Based on the sum size of the two largest tumors, tumor growth subtype, albumin, and age, the prognostic score allowed accurate preoperative risk stratification in HCC patients with PVTT, independent of Cheng's PVTT classification. [ABSTRACT FROM AUTHOR]