Hepatocellular carcinoma (HCC) and metastatic liver tumors (MLT) are the most common malignant liver lesions, each requiring distinct therapeutic approaches. Accurate differentiation between these malignancies is critical for appropriate treatment planning and prognostication. However, there is limited data on the performance of contrast-enhanced ultrasound liver imaging reporting and data system (CEUS-LI-RADS) in this differentiation.

To evaluate the diagnostic efficacy of the CEUS-LI-RADS in distinguishing between HCC and MLT in an expanded population at risk for both tumors.

Between June 2017 and January 2022, 108 patients with HCC and 138 patients with MLT who were pathologically diagnosed, where included in this retrospective study. Two radiologists independently reviewed the CEUS features and liver imaging reporting and data system (LI-RADS) categories of the lesions, and based on their consensus, we calculated the diagnostic performance, including the area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of the CEUS-LI-RADS criteria.

The sensitivity, specificity, and accuracy of CEUS LI-RADS category 5 (CEUS-LR-5) for predicting HCC were 49.1% [95% confidence interval (CI)) 39.3-58.9], 97.1% (95% CI 92.7-99.2), and 76%, respectively, whereas the corresponding values for LI-RADS category M (LR-M) for diagnosing MLT were 89.1% (95%CI 82.7-93.8), 72.2% (95%CI 62.8-80.4), and 81.7%, respectively. Based on current LR-M criteria, a small proportion of HCCs were classified as LR-M due to the presence of early cessation (45-60s). In the analysis of the MLT subgroup, we found that the tumor size affects the distribution of LI-RADS (LR) classification in the subgroup (p = 0.037), and LI-RADS category 3 (LR-3) classification was observed more frequently in tumors of small size (≤3cm) than those of larger size. In addition, LR-3 metastases were more frequently characterized by hypovascular supply.

CEUS-LI-RADS demonstrates high specificity in distinguishing HCC from MLT, providing a reliable noninvasive diagnostic tool that can enhance clinical decision-making. These findings are clinically significant as they can improve patient management and treatment outcomes, and they underscore the need for future research to refine and expand the use of CEUS-LI-RADS in diverse clinical settings.

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.

Patients with cirrhosis undergo frequent abdominal imaging including semiannual hepatocellular carcinoma (HCC) screening, with results released immediately via the patient portal. We characterized time from patient review to patient-provider communication (PPC) for patients with abnormal liver imaging results.

We identified patients with cirrhosis enrolled in the patient portal with a new abnormal liver lesion (LI-RADS, LR) on ambulatory liver ultrasound (US) or multiphasic computed tomography/magnetic resonance imaging. Imaging findings were grouped into low-risk (US-2, LR-2), intermediate-risk (US-3, LR-3), and high-risk (LR-4, LR-5, LR-M, LR-TIV) results. We extracted three date-time events from the electronic health record, including result release to the patient, patient review of the result, and result-related PPC. We compared communication methods and the median time with PPC after patient review of results between groups.

The cohort included 133 patients (median age, 62 years, 56% male) with 34 (25.6%) low-risk, 61 (45.9%) intermediate-risk, and 38 (28.6%) high-risk results. PPC for high-risk results was predominantly via telephone calls (60.5%), whereas portal messages were most commonly used for low- and intermediate-risk results (61.8% and 45.9%, respectively; P < .001). For patients who reviewed their result on the portal, most (79.3%) reviewed the result before PPC, among whom the median time between review and PPC was 55.8 (IQR, 22.0-219.0), 167 (IQR, 42.7-324.0), and 47.3 (IQR, 25.8-78.8) hours for low-, intermediate-, and high-risk results, respectively (P = .02).

Portal-based review of abnormal imaging results by patients before provider communication is common, including results concerning a new HCC diagnosis. Further studies are needed to evaluate patient-reported outcomes, such as psychological distress, associated with this method of disclosing cancer-related results.

Abbreviated MRI (AMRI) has been proposed as an alternative to ultrasound for hepatocellular carcinoma (HCC) surveillance; however, comparative data for AMRI and ultrasound are needed. Thus, we evaluated the sensitivity and specificity of dynamic contrast-enhanced (DCE)-AMRI and ultrasound for early-stage HCC detection in patients with cirrhosis.

We conducted a multicenter retrospective case-control study among patients with cirrhosis (cases with early-stage HCC as per Milan Criteria; controls without HCC) who underwent an ultrasound and a DCE-MRI within a 6-month period between 2012 and 2019. HCC diagnosis was confirmed by imaging alone in 85% and by histopathology in 15% of patients. Dynamic AMRI examinations were simulated from the full MRI by selecting relevant sequences. Independent, blinded interpretations of ultrasounds and AMRI results were performed using Liver Imaging Reporting and Data System algorithms. Ultrasounds were considered positive if US-3 observations were detected. AMRI was considered positive if LR-4, LR-5, or LR-M were detected. Per-patient sensitivity and specificity for early-stage HCC detection were estimated, and cross-modality differences were tested.

We included 216 cases and 432 controls. Patient-level sensitivity and specificity of AMRI were significantly higher compared with ultrasound: 80.1% (95% CI 76.1-83.6) vs. 71.1% (95% CI 66.6-75.2), p <0.001, and 91.9% (95% CI 89.9-93.5) vs. 72.3% (95% CI 69.3-75.2), p <0.001, respectively. AMRI sensitivity was significantly higher compared with ultrasound among patients with Child-Pugh B cirrhosis (80.8% vs. 57.4%, p <0.001) but not among those with Child-Pugh A (84.7% vs. 78.6%, p = 0.07) or Child-Pugh C cirrhosis (52.6% vs. 68.4%, p = 0.18).

Dynamic AMRI may be more sensitive and specific for early-stage HCC detection in patients with cirrhosis compared with ultrasound, although its relative benefit might be smaller in patients with Child-Pugh A cirrhosis. Larger direct comparative data sets are needed, particularly among patients with Child-Pugh C cirrhosis who may benefit from alternative surveillance strategies.

Abbreviated MRI (AMRI) is increasingly recognized as an alternative to ultrasound for hepatocellular carcinoma (HCC) surveillance. However, existing data are limited by single-center samples, spectrum bias, and lack of comparative data for AMRI vs. ultrasound. We found that AMRI had significantly higher per-patient sensitivity and specificity compared with ultrasound for the detection of early-stage HCC, although its relative benefit might be smaller in patients with Child-Pugh A cirrhosis, and both modalities underperformed in patients with Child-Pugh C cirrhosis. If sufficiently validated, AMRI could be adopted into practice guidelines for HCC surveillance and serve as a preferred alternative in select subgroups of patients.

Purpose: Use a tailored version of the Quality Assessment of Diagnostic Accuracy Studies tool to evaluate risk of bias and applicability across LIRADS related publications. Method: A tailored QUADAS-2 tool was created through consensus approach to assess risk of bias and applicability across 37 LI-RADS related publications. Studies were selected from 2017 to 2022 using the assistance of experienced hospital librarians to search for studies evaluating the diagnostic accuracy of CT, MRI, or contrast-enhanced ultrasound for HCC using LI-RADS through multiple different databases. QUADAS-2 assessments were performed in duplicate and independently by 2 authors with experience using the QUADAS-2 tool. Disagreements were resolved with a third expert reviewer. Consensus QUADAS-2 assessments were tabulated for each domain. Results: Using the tailored QUADAS-2 tool, 31 of the 37 included LI-RADS studies were assessed as high risk of bias, and 9 out of 37 studies demonstrated concerns for applicability. Patient selection (21 out of 37 studies) and flow/timing (24 out of 37 studies) domains demonstrated the highest risk of bias. 6 out of 37 studies in the index domain demonstrated high risk of bias. 2 out of 37 studies showed high risk of bias in the reference standard domain. Conclusion: A significant proportion of LI-RADS research is at risk of bias with concerns for applicability. Identifying risk of bias in such research is essential to recognize limitations of a study that may affect the validity of the results. Areas for improvement in LI-RADS research include reducing selection bias, avoiding inappropriate exclusions, and decreasing verification bias.

MRI is a potential alternative to ultrasound for hepatocellular carcinoma (HCC) detection. We evaluated the impact of ultrasound and dynamic abbreviated MRI (AMRI) exam quality on early-stage HCC detection.

We conducted a multicenter case-control study among patients with cirrhosis (cases with early-stage HCC per Milan Criteria; controls without HCC) who underwent both a liver ultrasound and dynamic contrast-enhanced (DCE) AMRI within 6 months in 2012-2019. Two radiologists performed independent, blinded interpretations of both exams for HCC detection and scored exam quality as no/mild, moderate, or severe limitations. Associations between exam quality, patient characteristics, and HCC detection were assessed by odds ratios (OR).

Of 216 cases and 432 controls, severe limitations were reported in 7% and 8% of ultrasounds and DCE-AMRIs, respectively. Severe limitations at ultrasound were associated with obesity (OR 2.08, 95%CI [1.32-3.32]) and metabolic dysfunction-associated steatotic liver disease (MASLD) (OR 1.98 [1.12-3.44]) but not for DCE-AMRI. Decompensated cirrhosis (Child-Pugh C) was associated with severe limitations for both ultrasound (OR 2.54 [1.37-4.58]) and DCE-AMRI (OR 3.96 [2.36-6.58]). Compared to exams with no/mild limitations, exams with severe limitations had lower sensitivity for ultrasound (79.6% vs. 21.7%, P < 0.001) and AMRI (86.1% vs. 50.0%, P = 0.001). In patients in whom ultrasound was severely limited, DCE-AMRI had significantly higher odds of early-stage HCC detection than ultrasound (OR 8.23 [1.25-54.02]).

HCC detection by DCE-AMRI may be preferred in patients with severe limitations at ultrasound due to obesity and MASLD. Both modalities remain limited for patients with decompensated cirrhosis, for whom alternative strategies may be needed.

The Liver Imaging Reporting and Data System (LI-RADS, LR) provides a framework for diagnosing hepatocellular carcinoma (HCC, LR-5). However, not all HCCs meet LR-5 criteria and are instead categorized as LR-M, probably or definitely malignant but not specific for HCC, necessitating biopsy for diagnosis. The purpose is to identify factors associated with HCC in LR-M observations.

This is an IRB-approved, retrospective analysis of participants from 8 institutions that had a LR-M observation on CT or MRI with corresponding histopathologic diagnosis. Demographics and biochemical data were examined. Central review using the LI-RADS v2018 algorithm was performed. Kappa statistics defined inter-reader agreement. Random forest and logistic regression analyses generated a model for HCC diagnosis.

162 participants with 162 LR-M observations were included. 46% of observations (74/162) were HCC and 37% were cholangiocarcinoma (60/162). Two of 34 imaging features- observation size and intra-lesion iron- showed moderate to strong inter-reader agreement (Kappa ≥ 0.60) while the remainder showed weak or no agreement (Kappa < 0.60). Random forest analysis showed biochemical features to be more predictive of HCC than imaging features. Logistic regression analysis of a model based on INR and AFP provided a 72% sensitivity and 61% specificity for HCC by Youden's index and a 90% specificity threshold yielded 38% sensitivity, 75% positive predictive value, and 66% negative predictive value.

Our results show INR and AFP are associated with HCC in LR-M observations. A high-specificity threshold may assist in the non-invasive diagnosis of HCC in the appropriate setting. In certain at-risk patients with a LR-M observation on diagnostic imaging, serum AFP and INR maybe useful tools for the non-invasive diagnosis of HCC.

The aim of this study was to evaluate the quality of structured reporting of MRI examinations in patients at risk for HCC using the Liver Imaging Reporting and Data System (LI-RADS) created during the daily clinical routine.In this retrospective study, MRI examinations of 163 patients under HCC surveillance and HCC follow-up were analyzed. The study cohort included a group of 76 patients whose examinations were performed using free-text reporting and a group of 87 patients with structured template reporting based on the LI-RADS criteria. The diagnostic accuracy of the specified LI-RADS category was analyzed for both groups. The impact of structured reporting and the frequency of reporting of the major and ancillary LI-RADS features in free-text reports and structured reports were compared using the χ²-test.Liver lesions were classified according to LI-RADS significantly more often in the structured reports (91.4%) than in the unstructured free-text reports (82.6%) (p < 0.01). Most relevant major LI-RADS criteria were described significantly more frequently when using the structured report template compared to free text, e.g., arterial hyperenhancement 100% vs. 92.5% (p < 0.01) and washout 93.4% vs. 79.7% (p < 0.01). Only the documentation of threshold growth was not significantly improved, but absolute lesion size was reported significantly more often within the structured reports. The diagnostic accuracy of the LI-RADS category was higher for the structured reports than for the free-text reports (82.3% vs. 63.9%).Structured reporting improves LI-RADS documentation in MRI reports of patients at risk for HCC and may help with multidisciplinary communication and patient management. · Structured reporting showed improved documentation of key features for LI-RADS classification compared to nonstructured MRI reports.. · Structured reports improve the categorization of liver lesions according to LI-RADS in patients at risk for HCC.. · Nelles C, Wagner A, Lennartz S et al. Clinical Benefit of Structured Reporting Using the Liver Imaging Reporting and Data System (LI-RADS) in MRI in Patients at Risk for Hepatocellular Carcinoma. Rofo 2025; DOI 10.1055/a-2553-1392.

The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).

This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.

In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%-79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%-87%], 84% [95% CI: 79%-89%], 88% [95% CI: 83%-92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%-97%).

The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

The Liver Imaging Reporting and Data System (LI-RADS) does not consider factors extrinsic to the observation of interest, such as concurrent LR-5 observations.

To evaluate whether the presence of a concurrent LR-5 observation is associated with a difference in the probability that LR-3 or LR-4 observations represent hepatocellular carcinoma (HCC) through an individual participant data (IPD) meta-analysis.

Multiple databases were searched from 1/2014 to 2/2023 for studies evaluating the diagnostic accuracy of CT/MRI for HCC using LI-RADS v2014/2017/2018. The search strategy, study selection, and data collection process can be found at https://osf.io/rpg8x . Using a generalized linear mixed model (GLMM), IPD were pooled across studies and modeled simultaneously with a one-stage meta-analysis approach to estimate positive predictive value (PPV) of LR-3 and LR-4 observations without and with concurrent LR-5 for the diagnosis of HCC. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).

Twenty-nine studies comprising 2591 observations in 1456 patients (mean age 59 years, 1083 [74%] male) were included. 587/1960 (29.9%) LR-3 observations in 1009 patients had concurrent LR-5. The PPV for LR-3 observations with concurrent LR-5 was not significantly different from the PPV without LR-5 (45.4% vs 37.1%, p = 0.63). 264/631 (41.8%) LR-4 observations in 447 patients had concurrent LR-5. The PPV for LR-4 observations with concurrent LR-5 was not significantly different from LR-4 observations without concurrent LR-5 (88.6% vs 69.5%, p = 0.08). A sensitivity analysis for low-risk of bias studies (n = 9) did not differ from the primary analysis.

The presence of concurrent LR-5 was not significantly associated with differences in PPV for HCC in LR-3 or LR-4 observations, supporting the current LI-RADS paradigm, wherein the presence of synchronous LR-5 may not alter the categorization of LR-3 and LR-4 observations.

Hepatocellular carcinoma (HCC) may be diagnosed and further subclassified in surgical specimen as per the recent World Health Organization (WHO) classification into several distinct subtypes with prognostic implications. The aim of this study was to apply this WHO classification on fine-needle aspiration biopsy (FNAB) samples of HCC and describe their features.

This was a retrospective analysis of all ultrasound-guided FNAB of liver mass lesions in patients with suspected HCC (n = 164) over a 7-year period. Detailed morphological assessment of cytopathological features and grading was done and correlated with each other. HCC was subtyped further in cases with available cell blocks (n = 126).

A total of 164 cases of HCC were evaluated on FNAB with age range of 18-88 years (mean, 60 years), and with 140 (85.4%) male and 24 (14.6%) female patients. Grading performed on 160 cases of HCC (after excluding fibrolamellar HCC) revealed 23 well differentiated, 127 moderately differentiated, and 10 poorly differentiated HCCs. Subtyping was feasible in 126 cases, of which 26 cases (20.6%) showed specific subtypes that were steatohepatitic (8), lymphocyte-rich (8), fibrolamellar (4), neutrophil-rich (3), macrotrabecular massive (2), and clear cell HCC (1) with remaining cases (100) being conventional HCC, no special type.

The study demonstrates the feasibility of subtyping HCC (as per the current WHO classification) for the first time on FNAB with cell blocks that carries implication for prognostication and emphasizes the importance of obtaining tissue diagnosis by FNAB with cell blocks.

Timely and accurate diagnosis of hepatocellular carcinoma (HCC) is essential for improving patient outcomes and guiding treatment. This multicenter study aimed to optimize the diagnostic workflow for HCC through a step-wise combination of CT/MRI and contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS).

This was a multicenter, retrospective analysis of prospectively recruited high-risk HCC participants with liver observations from 4 institutions, between January 2017 and December 2021. These participants initially underwent CT/MRI followed by CEUS, with observations categorized according to CT/MRI/CEUS LI-RADS. Three step-wise diagnostic strategies were evaluated, starting with CT/MRI and followed by CEUS, and compared to CT/MRI LI-RADS alone. Performance metrics included AUC, accuracy, sensitivity, specificity, PPV, and NPV, using pathology or over one year of follow-up as standards. The impact on clinical decisions was measured by false-negative, false-positive, and biopsy rates.

Of 1264 participants, 874 (69%) were confirmed as HCC. The step-wise strategies outperformed CT/MRI LI-RADS. Strategy-3, which involved subsequent CEUS for CT/MRI LR-3/4 observations, significantly improved sensitivity (88.8% vs. 79.9%, P < 0.001) while maintaining comparable specificity (88.2% vs. 91.3%, P > 0.05). Strategy-3 reduced biopsy rate (31.5-22.4%, P = 0.028) and decreased false-negative rate (20.1-11.2%, P < 0.001). Additionally, 96% (55/57) of CT/MRI LR-3 and 97% (77/79) of CT/MRI LR-4 observations were accurately diagnosed and treated as HCC, with 61% (74/121) of CT/MRI LR-4 observations avoiding biopsy with CEUS-assisted.

A step-wise approach using CT/MRI followed by CEUS for LR-3/4 observations improved the diagnostic performance and further refined clinical decision-making in HCC.

Clinical Trial Registration Number: ChiCTR-DDD-16010089.

Background The Liver Imaging Reporting and Data System (LI-RADS) criteria have not been validated for patients with noncirrhotic chronic hepatitis C (CHC), who are at a greater risk for hepatocellular carcinoma (HCC) than the general population. Purpose To evaluate the diagnostic performance of LI-RADS category 5 (LR-5, indicating definite HCC) observations for HCC using CT and MRI in patients with noncirrhotic CHC and to compare these findings with those in patients with cirrhotic CHC. Materials and Methods This retrospective study included patients without cirrhosis with CHC with focal hepatic nodules of 1 cm or greater on dynamic CT or MRI scans who underwent pathologic confirmation at two university hospitals from August 2002 to February 2022. This group served as the test dataset. The primary outcome was the diagnostic performance of LR-5 for HCC using CT and MRI. When LI-RADS categorization differed between CT and MRI, the MRI-based classification was used as the definitive category. Results were validated using a dataset of patients with CHC from two additional hospitals based on the clinical composite reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. Results The test dataset comprised 458 patients (mean age, 64 years ± 9 [SD]; 350 male; 219 without cirrhosis, 239 with cirrhosis). For noncirrhotic livers, the LR-5 criteria achieved an AUC, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.90 (95% CI: 0.86, 0.93), 85.1% (95% CI: 80.6, 89.7), 82.4% (95% CI: 77.0, 87.8), 97.6% (95% CI: 93.0, 100.0), 99.4% (95% CI: 98.2, 100.0), and 54.7% (95% CI: 43.4, 65.9), respectively. The AUC for LR-5 observations in diagnosing HCC was higher in the noncirrhotic liver group compared with the cirrhotic liver group (AUC, 0.90 [95% CI: 0.86, 0.93] vs 0.79 [95% CI: 0.74, 0.84]; P = .002). The diagnostic performance of the LR-5 criteria for diagnosing HCC was also excellent in patients with noncirrhotic CHC in the validation dataset, which included 155 lesions from 103 patients (mean age, 68 years ± 12; 146 male). The AUC, accuracy, sensitivity, specificity, PPV, and NPV in the validation dataset were 0.91 (95% CI: 0.84, 0.97), 96.1% (95% CI: 93.1, 99.2), 82.9% (95% CI: 70.4, 95.3), 100%, 100%, and 95.2% (95% CI: 91.5, 99.0), respectively. Conclusion The diagnostic performance of LR-5 for HCC in patients with noncirrhotic CHC was comparable to that in patients with cirrhosis across various clinical settings. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Schöllnast in this issue.

Alpha-fetoprotein (AFP) level and its changes in chronic hepatitis B (CHB) may influence the risk of future hepatocellular carcinoma (HCC). This study aims to evaluate the HCC risk in CHB patients with no overt HCC but with elevated AFP level and to explore the prognostic role of longitudinal changes in AFP and liver-related laboratory values. This multicentre cohort study included 10,639 CHB patients without a history of HCC from seven medical facilities in South Korea. Patients with a baseline serum AFP test and no HCC diagnosis on imaging within 3 months were included. Patients were categorised into high-AFP (≥ 10 ng/mL) and normal-AFP (< 10 ng/mL) groups. The primary outcome was the incidence of HCC within 2 years, with secondary outcomes focused on longitudinal changes in AFP and liver-related laboratory values. Propensity score matching (PSM) and Cox proportional hazard models were used to assess HCC risk. After 1:4 PSM, 1278 high-AFP and 3731 normal-AFP patients were analysed. The high-AFP group had a significantly higher 2-year incidence of HCC (HR: 4.29; 95% CI: 3.31-5.57). AFP levels increased in patients who developed HCC in both groups (p < 0.01). Among the high-AFP group, patients who did not develop HCC had elevated baseline alanine aminotransferase levels (p < 0.01), which decreased during follow-up (p < 0.01) unlike those who developed HCC. In conclusion, baseline AFP elevation in CHB patients is associated with an increased risk of developing HCC within 2 years. Longitudinal monitoring of AFP and liver-related laboratory values can help in risk stratification.

One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis.

The LCN consists of a Scientific Data Coordinating Center and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations. The Cohort Committee developed the study protocol with the input of the steering committee.

The LCN developed a prospective cohort study to describe and predict the rates of incident clinical events pertaining to first decompensation and patient-reported outcomes. The LCN developed a pragmatic definition of compensated cirrhosis incorporating clinical, laboratory, imaging, and histological criteria. Definitions of incident and recompensated ascites, overt hepatic encephalopathy, variceal hemorrhage, bleeding because of portal gastropathy, and hepatocellular carcinoma were also codified.

The LCN Cohort Study design will inform the natural history of cirrhosis in contemporary patients with compensated cirrhosis. The LCN Definitions and Measures Committee developed criteria for the definition of cirrhosis to standardize entry into this multicenter cohort study and standardized criteria for liver-related outcome measures. This effort has produced definitions intended to be both sensitive and specific as well as easily operationalized by study staff such that outcomes critical to the LCN cohort are identified and reported in an accurate and generalizable fashion.

NCT05740358.

For many cancers, biomarkers have served as an important tool across the cancer care continuum from risk stratification and early detection to diagnosis and treatment. Alpha-fetoprotein (AFP) remains one of the few validated biomarkers for patients with HCC. Although AFP has shown potential for each of these steps, its performance, when used alone, has often been suboptimal. There continue to be discordant recommendations about AFP's value when combined with ultrasound for surveillance, as well as its role in diagnostic algorithms. Conversely, high AFP levels are associated with aggressive tumor biology and survival, so it remains a key factor for the selection of candidates for liver transplant. There have been immense efforts to identify and validate additional biomarkers for each of these steps in the HCC care continuum. Indeed, biomarker panels have shown promising data for HCC risk stratification and surveillance among patients with cirrhosis, as well as prognostication and detection of minimal residual disease in patients undergoing HCC treatment. Several large prospective studies are currently ongoing to evaluate the role of these emerging biomarkers in clinical practice.

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.

The value of hepatocellular carcinoma screening is defined by the balance of benefits from early tumor detection vs harms because of false-positive results. We evaluated the value of a mailed outreach strategy for hepatocellular carcinoma screening in patients with cirrhosis.

We conducted a multicenter pragmatic randomized clinical trial comparing mailed outreach for hepatocellular carcinoma screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at 3 health systems from March 2018 to September 2021. Outcomes of interest were early stage hepatocellular carcinoma detection (ie, screening benefit) and diagnostic evaluation for false-positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses.

Of 125 patients diagnosed with hepatocellular carcinoma (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan criteria. Early tumor detection did not statistically significantly differ between the outreach and usual care arms (64.2% vs 79.3%; P = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%; P = .95) with 5.9% in both arms having mild harms; 4.0% and 3.8%, respectively, with moderate harms; and 0.9% and 1.0%, respectively, with severe harms.

Most patients enrolled in hepatocellular carcinoma screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not increase early hepatocellular carcinoma detection or physical harms compared with usual care.

NCT02582918 and NCT03756051.

Promoting the early detection and diagnosis of hepatocellular carcinoma (HCC) is a critical strategy to improve patient outcomes as this can lead to greater access to curative treatments. This review highlights the diagnostic tests for HCC, including the use of the Liver Imaging Reporting and Data System systems and histopathology. Staging is essential for informing prognosis and guiding treatment decisions; this review also covers a widely used and well-validated staging system called the Barcelona-Clinic Liver Cancer (BCLC) algorithm. The BCLC incorporates tumor status, liver function, and patient performance to stage patients with newly diagnosed HCC.

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.

Hepatocellular carcinoma (HCC) is characterized by a high mortality rate. The Liver Imaging Reporting and Data System (LI-RADS) results in a considerable number of indeterminate observations, rendering an accurate diagnosis difficult.

We developed four deep learning models for diagnosing HCC on computed tomography (CT) via a training-validation-testing approach. Thin-slice triphasic CT liver images and relevant clinical information were collected and processed for deep learning. HCC was diagnosed and verified via a 12-month clinical composite reference standard. CT observations among at-risk patients were annotated using LI-RADS. Diagnostic performance was assessed by internal validation and independent external testing. We conducted sensitivity analyses of different subgroups, deep learning explainability evaluation, and misclassification analysis.

From 2,832 patients and 4,305 CT observations, the best-performing model was Spatio-Temporal 3D Convolution Network (ST3DCN), achieving area under receiver-operating-characteristic curves (AUCs) of 0.919 (95% CI, 0.903-0.935) and 0.901 (95% CI, 0.879-0.924) at the observation (n = 1,077) and patient (n = 685) levels, respectively during internal validation, compared with 0.839 (95% CI, 0.814-0.864) and 0.822 (95% CI, 0.790-0.853), respectively for standard of care radiological interpretation. The negative predictive values of ST3DCN were 0.966 (95% CI, 0.954-0.979) and 0.951 (95% CI, 0.931-0.971), respectively. The observation-level AUCs among at-risk patients, 2-5-cm observations, and singular portovenous phase analysis of ST3DCN were 0.899 (95% CI, 0.874-0.924), 0.872 (95% CI, 0.838-0.909) and 0.912 (95% CI, 0.895-0.929), respectively. In external testing (551/717 patients/observations), the AUC of ST3DCN was 0.901 (95% CI, 0.877-0.924), which was non-inferior to radiological interpretation (AUC 0.900; 95% CI, 0.877--923).

ST3DCN achieved strong, robust performance for accurate HCC diagnosis on CT. Thus, deep learning can expedite and improve the process of diagnosing HCC.

The clinical applicability of deep learning in HCC diagnosis is potentially huge, especially considering the expected increase in the incidence and mortality of HCC worldwide. Early diagnosis through deep learning can lead to earlier definitive management, particularly for at-risk patients. The model can be broadly deployed for patients undergoing a triphasic contrast CT scan of the liver to reduce the currently high mortality rate of HCC.

Objective  The aims of this study are to compare the multiphasic contrast-enhanced computed tomography (CECT) characteristics of infiltrative hepatocellular carcinoma (HCC) with nodular HCC and to assess the conspicuity of infiltrative HCC on different phases of CECT. Materials and Methods  This retrospective study comprised consecutive treatment-naive cirrhotic patients diagnosed with infiltrative and nodular HCC between January 2020 and December 2021 based on a multiphasic CECT (comprising arterial, portal venous, and delayed phases). The diagnosis of HCC was based on the Liver Imaging Reporting and Data System (LI-RADS) v2018 criteria (LR-4 and LR-5 lesions). Infiltrative HCCs are characterized by large, irregular, permeative lesions spread over multiple liver segments or lobes. Nodular HCCs comprise well-defined tumor nodules. Two radiologists independently reviewed all CT images. Additionally, lesion conspicuity on the arterial, portal venous, and delayed phases was assessed. Results  One hundred fifty-eight patients (117 nodular and 41 infiltrative HCCs; mean age: 55.6 ± 17.2 years; 90 [56.9%] males) were included. Arterial phase hyperenhancement, portal venous/delayed phase washout, and delayed phase enhancing capsule were significantly associated with nodular HCCs ( p  = 0.002, 0.0001, and <0.0001, respectively). Portal vein, hepatic vein thrombosis, biliary dilatation, and ascites were significantly associated with infiltrative HCCs ( p  < 0.0001, 0.004, <0.0001, and 0.003, respectively). The interobserver agreement for the conspicuity of infiltrative HCC was the highest for the delayed phase (weighted kappa = 0.611). Conclusion  Infiltrative HCCs show the major LI-RADS features less frequently compared with nodular HCCs, and venous thrombosis is an important clue to the diagnosis. The delayed phase of multiphasic CECT is critical to identifying these lesions.

Background: Guidelines suggest the Liver Imaging Reporting and Data System (LI-RADS) may not be applicable for some populations at risk for hepatocellular carcinoma (HCC). However, data assessing the association of HCC risk factors with LI-RADS major features are lacking. Purpose: To evaluate whether the association between HCC risk factors and each CT/MRI LI-RADS major feature differs among individuals at-risk for HCC. Methods: Databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched from 2014 to 2022. Individual participant data (IPD) were extracted from studies evaluating HCC diagnosis using CT/MRI LI-RADS and reporting HCC risk factors. IPD from studies were pooled and modelled with one-stage meta-regressions. Interactions were assessed between major features and HCC risk factors, including age, sex, cirrhosis, chronic hepatitis B virus (HBV), and study location. A mixed effects model that included the major features, as well as separate models that included interactions between each risk factor and each major feature, were fit. Differences in interactions across levels of each risk factor were calculated using adjusted odds-ratios (ORs), 95% confidence-intervals (CI), and z-tests. Risk of bias was assessed using QUADAS-2. (Protocol: https://osf.io/tdv7j/). Results: Across 23 studies (2958 patients and 3553 observations), the associations between LI-RADS major features and HCC were consistent across several HCC risk factors (P-value range: .09-.99). A sensitivity analysis among the 4 studies with a low risk of bias did not differ from the primary analysis. Conclusion: The association between CT/MRI LI-RADS major features and HCC risk factors do not significantly differ in individuals at-risk for HCC. These findings suggest that CT/MR LI-RADS should be applied to all patients considered at risk by LI-RADS without modification or exclusions, regardless of the presence or absence of the risk factors evaluated in this study.

Young adults contribute substantially to the social economy. However, the number of young adults with liver cancer has increased recently. In addition, the mortality rate of these patients is high.

This retrospective study investigated the risk factors of young patients diagnosed with liver cancer over the past 12 years.

The risk factors of liver cancer, including male, HBV infection, and family history of diseases, were more common in young patients. Nearly 80% of young patients (198/253) were tested as positive HBsAg. However, most of these patients did not visit doctors regularly, as recommended. Thus, 55.7% of young patients were diagnosed with advanced liver cancer. The aspartate aminotransferase (AST) levels were independently associated with advanced liver cancer (OR = 4.262, 95% CI = 1.559-11.65, P = 0.005) in the multivariable logistic regression. The 1-year survival rate of these patients was 19.4%.

The high-risk factors of liver cancer are common in young patients. The poor adherence to regularly visited doctors in young patients might contribute to the high ratio of advanced liver cancer. The 1-year survival rate of these patients is low. Improving patient's adherence via mobile healthcare platform and monitoring serum AST levels might decrease the incidence and mortality of liver cancer in young adults.

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.

Background Prediction of the tumor growth rates is clinically important in patients with hepatocellular carcinoma (HCC), but previous studies have presented conflicting results and generally lacked radiologic evaluations. Purpose To evaluate the percentage of rapidly growing early-stage HCCs in each Liver Imaging Reporting and Data System (LI-RADS) category and to identify prognostic factors associated with rapid growth. Materials and Methods Retrospective study of patients with risk factors for HCC and those with surgically proven early-stage HCC who underwent two or more preoperative multiphasic CT or MRI examinations between January 2016 and December 2020. LI-RADS categories were assigned according to the baseline CT or MRI results. The tumor volume doubling time (TVDT) was calculated from the tumor volumes measured at the two examinations. The growth rate was classified as rapid (TVDT < 3 months), intermediate (TVDT = 3-9 months), or indolent (TVDT > 9 months). The percentage of rapidly growing HCCs was compared among the LI-RADS categories, and multivariable logistic regression was used to identify factors associated with rapidly growing HCC. Results In 322 patients (mean age, 61 years ± 9 [SD]; 249 men) with 345 HCCs (30 LR-3, 64 LR-4, 221 LR-5, and 30 LR-M category), the median TVDT of HCC was 131 days (IQR, 87-233) and 27.0% of HCCs showed rapid growth. The growth rates differed among the LI-RADS categories, with a higher percentage of rapidly growing HCCs observed for LR-M HCCs than for LR-3 (70.0% vs 3.3%, P < .001), LR-4 (70.0% vs 12.5%, P < .001), or LR-5 (70.0% vs 28.5%, P < .001) HCCs. An α-fetoprotein level greater than 400 ng/mL (adjusted odds ratio [OR], 2.54; 95% CI: 1.16, 5.54; P = .02), baseline tumor diameter (adjusted OR, 0.65; 95% CI: 0.48, 0.87; P = .004), and LR-M category (adjusted OR, 9.26; 95% CI: 3.70, 23.16; P < .001) were independently associated with higher odds of rapid growth. Conclusion Among early-stage HCCs, LR-M category was an independent factor for rapid growth, observed in 70% of HCCs. © RSNA, 2024 Supplemental material is available for this article.

Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis.

Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the proportion of time covered (PTC) by screening. All patients were included in intention-to-screen analyses.

All 2872 participants (median age 61.3 years; 32.3% women) were included in intention-to-screen analyses. Screening process completion was observed in 6.6% (95% CI: 5.3% to 7.9%) of patients randomised to outreach and 3.3% (95% CI: 2.4% to 4.3%) of those randomised to usual care (OR 2.05, 95% CI: 1.44 to 2.92). The intervention increased HCC screening process completion across most subgroups including age, sex, race and ethnicity, Child-Turcotte-Pugh class and health system. PTC was also significantly higher in the outreach arm than usual care (mean 37.5% vs 28.2%; RR 1.33, 95% CI: 1.31 to 1.35). Despite screening underuse, most HCC in both arms were detected at an early stage.

Mailed outreach plus navigation significantly increased HCC screening process completion versus usual care in patients with cirrhosis, with a consistent effect across most examined subgroups. However, screening completion remained suboptimal in both arms, underscoring a need for more intensive interventions.

NCT02582918.

Computed tomography (CT)/magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS, LR) category 5 has high specificity and modest sensitivity for diagnosis of hepatocellular carcinoma (HCC). The purpose of this study was to compare the diagnostic performance of LR-5 vs combined LR-4 and LR-5 (LR-4/5) for HCC diagnosis.

MEDLINE and EMBASE databases through January 03, 2023 were searched for studies reporting the performance of LR-5 and combined LR-4/5 for HCC diagnosis, using CT/MRI LI-RADS version 2014, 2017, or 2018. A bivariate random-effects model was used to calculate the pooled per-observation diagnostic performance. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material.

Sixty-nine studies (15,108 observations, 9928 (65.7%) HCCs) were included. Compared to LR-5, combined LR-4/5 showed significantly higher pooled sensitivity (83.0% (95% CI [80.3-85.8%]) vs 65.7% (95% CI [62.4-69.1%]); p < 0.001), lower pooled specificity (75.0% (95% CI [70.5-79.6%]) vs 91.7% (95% CI [90.2-93.1%]); p < 0.001), lower pooled positive likelihood ratio (3.60 (95% CI [3.06-4.23]) vs 6.18 (95% CI [5.35-7.14]); p < 0.001), and lower pooled negative likelihood ratio (0.22 (95% CI [0.19-0.25]) vs 0.38 (95% CI [0.35-0.41]) vs; p < 0.001). Similar results were seen in all subgroups.

Our meta-analysis showed that combining LR-4 and LR-5 would increase sensitivity but decrease specificity, positive likelihood ratio, and negative likelihood ratio. These findings may inform management guidelines and individualized management.

This meta-analysis estimated the magnitude of changes in the sensitivity and specificity of imaging criteria when LI-RADS categories 4 and 5 were combined; these findings can inform management guidelines and individualized management.

There is no single worldwide reporting system for liver imaging, partly due to regional needs. Combining LI-RADS categories 4 and 5 increased sensitivity and decreased specificity and positive and negative likelihood ratios. Changes in the sensitivity and specificity of imaging criteria can inform management guidelines and individualized management.

Indeterminate liver nodules (ILNs) are frequently encountered on diagnostic imaging after positive hepatocellular carcinoma (HCC) surveillance results, but their natural history remains unclear.

We conducted a multicenter retrospective cohort study among patients with ≥1 newly detected LI-RADS 3 (LR-3) lesion ≥1 cm or LI-RADS 4 (LR-4) lesion of any size (per LI-RADS v2018) between January 2018 and December 2019. Patients were followed with repeat imaging at each site per institutional standard of care. Multivariable Fine-Gray models were used to evaluate associations between potential risk factors and patient-level time-to-HCC diagnosis, with death and liver transplantation as competing risks.

Of 307 patients with ILNs, 208 had LR-3 lesions, 83 had LR-4 lesions, and 16 had both LR-3 and LR-4 lesions. HCC incidence rates for patients with LR-3 and LR-4 lesions were 110 (95% CI 70-150) and 420 (95% CI 310-560) per 1,000 person-year, respectively. In multivariable analysis, incident HCC among patients with LR-3 lesions was associated with older age, thrombocytopenia (platelet count ≤150 ×10 9 /L), and elevated serum alpha-fetoprotein levels. Among those with LR-4 lesions, incident HCC was associated with a maximum lesion diameter >1 cm. Although most patients had follow-up computed tomography or magnetic resonance imaging, 13.7% had no follow-up imaging and another 14.3% had follow-up ultrasound only.

ILNs have a high but variable risk of HCC, with 4-fold higher risk in patients with LR-4 lesions than those with LR-3 lesions, highlighting a need for accurate risk stratification tools and close follow-up in this population.