Ultrasound-based steatosis grading system using 2D-attenuation imaging: An individual patient data meta-analysis with external validation.

BACKGROUND AND AIMS: Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. APPROACH AND RESULTS: A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references. CONCLUSIONS: ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.

Fat-containing hepatocellular carcinoma in patients with cirrhosis: proposal of a diagnostic modification regarding enhancement characteristics.

OBJECTIVES: The aim of this study was to develop and validate an algorithm for the non-invasive diagnosis of these fat-containing HCCs. METHODS: Eighty-four cirrhotic patients with 77 fat-containing HCCs and 11 non-HCC fat-containing nodules were retrospectively included. All MRIs were reviewed; nodule characteristics, European Association for the Study of the Liver (EASL) and LI-RADS classifications, and survival were collected. One of the major features of LI-RADS v2018 (non-rim-like arterial phase hyperenhancement [APHE]) was changed to include different enhancing patterns at arterial phase and a new fat-LI-RADS algorithm was created for fat-containing nodules in cirrhosis. Its diagnostic performance was evaluated in both a derivation and external validation cohort (external cohort including 58 fat-containing HCCs and 10 non-HCC fat nodules). Reproducibility of this new algorithm was assessed. RESULTS: In the derivation cohort, 54/77 (70.1%) fat-containing HCCs had APHE, 62/77 (80.5%) had enhancement compared to the nodule itself at arterial phase (APE), 43/77 (55.8%) had washout, and 20/77 (26.0%) had an enhancing capsule. EASL and LI-RADS had a sensitivity of 37.7% (29/77) and 36.4% (28/77), respectively, for the diagnosis of fat-containing HCC and both had a specificity of 100% (11/11). The new fat-LI-RADS algorithm increased sensitivity to 50.6% (39/77) without decreasing the specificity of 100% (11/11). The validation cohort confirmed the increased sensitivity, with a slight decrease in specificity. The concordance for the diagnosis of HCC for fat-LR5 was 85.3% (58/68). CONCLUSION: The new fat-LI-RADS algorithm proposed here significantly improves the performance of the non-invasive diagnosis of fat-containing HCC and thus could reduce the number of biopsies conducted for fat-containing HCCs. CLINICAL RELEVANCE STATEMENT: The European Association for the Study of the Liver and LI-RADS guidelines are poorly sensitive for the diagnosis of fat-containing HCC, mainly because of the low rate of arterial phase hyperenhancement (APHE) displayed by fat-containing HCC. Using all types of enhancement instead of APHE improves sensitivity of LI-RADS. KEY POINTS: • Fat-containing HCCs on MRI account for 7.5% of HCCs and have different imaging characteristics from non-fatty HCCs. • The European Association for the Study of the Liver and LI-RADS algorithms for the non-invasive diagnosis of HCC have low sensitivity for the diagnosis of fat-containing HCC with MRI (37.7% and 36.4%, respectively). • The new fat-LI-RADS, which includes a slight modification of the "arterial enhancement" criterion, improves the sensitivity for the diagnosis of fat-containing HCC using MRI, without degrading the specificity.

Defining textbook outcome for selective internal radiation therapy of hepatocellular carcinoma: an international expert study.

BACKGROUND: A textbook outcome (TO) is a composite indicator covering the entire intervention process in order to reflect the "ideal" intervention and be a surrogate for patient important outcomes. Selective internal radiation therapy (SIRT) is a complex multidisciplinary and multistep intervention facing the challenge of standardization. This expert opinion-based study aimed to define a TO for SIRT of hepatocellular carcinoma. METHODS: This study involved two steps: (1) the steering committee (4 interventional radiologists) first developed an extensive list of possible relevant items reflecting an optimal SIRT intervention based on a literature review and (2) then conducted an international and multidisciplinary survey which resulted in the final TO. This survey was online, from February to July 2021, and consisted three consecutive rounds with predefined settings. Experts were identified by contacting senior authors of randomized trials, large observational studies, or studies on quality improvement in SIRT. This study was strictly academic. RESULTS: A total of 50 items were included in the first round of the survey. A total of 29/40 experts (73%) responded, including 23 interventional radiologists (79%), three nuclear medicine physicians (10%), two hepatologists, and one oncologist, from 11 countries spanning three continents. The final TO consisted 11 parameters across six domains ("pre-intervention workup," "tumor targeting and dosimetry," "intervention," "post-90Y imaging," "length of hospital stay," and "complications"). Of these, all but one were applied in the institutions of > 80% of experts. CONCLUSIONS: This multidimensional indicator is a comprehensive standardization tool, suitable for routine care, clinical round, and research.

Diagnostic Performance of Attenuation to Stage Liver Steatosis with MRI Proton Density Fat Fraction as Reference: A Prospective Comparison of Three US Machines.

Background US tools to quantify liver fat content have recently been made clinically available by different vendors, but comparative data on their accuracy are lacking. Purpose To compare the diagnostic performances of the attenuation parameters of US machines from three different manufacturers (vendors 1, 2, and 3) in participants who underwent liver fat quantification with the MRI-derived proton density fat fraction (PDFF). Materials and Methods From July 2020 to June 2021, consecutive participants with chronic liver disease were enrolled in this prospective single-center study and underwent MRI PDFF quantification (reference standard) and US on the same day. US was performed with two different machines from among three vendors assessed. Areas under the receiver operating characteristic curve (AUCs) for the staging of liver steatosis (MRI PDFF: ≥5.5% for grade ≥S1 and ≥15.5% for grade ≥S2) were calculated in test and validation samples and then compared between vendors in the study sample. Results A total of 534 participants (mean age, 60 years ± 13 [SD]; 320 men) were evaluated. Failure of measurements occurred in less than 1% of participants for all vendors. Correlation coefficients with the MRI PDFF were 0.71, 0.73, and 0.54 for the attenuation coefficients of vendors 1, 2, and 3, respectively. In the test sample, AUCs for diagnosis of steatosis grade S1 and higher and grade S2 and higher were 0.89 and 0.93 for vendor 1 attenuation, 0.88 and 0.92 for vendor 2 attenuation, and 0.79 and 0.79 for vendor 3 attenuation, respectively. In the validation sample, a threshold value of 0.65 for vendor 1 and 0.66 for vendor 2 yielded sensitivity of 77% and 84% and specificity of 78% and 85%, respectively, for diagnosis of grade S1 and higher. Vendor 2 attenuation had greater AUCs than vendor 3 attenuation (P = .001 and P = .003) for diagnosis of grade S1 and higher and grade S2 and higher, respectively, and vender 2 had greater AUCs for attenuation than vendor 1 for diagnosis of grade S2 and higher (P = .04). For all vendors, attenuation was not associated with liver stiffness (correlation coefficients <0.05). Conclusion To stage liver steatosis, attenuation coefficient accuracy varied among US devices across vendors when using MRI proton density fat fraction quantification as the reference standard, with some demonstrating excellent diagnostic performance and similar cutoff values. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Dubinsky in this issue.

Transient Versus Two-Dimensional Shear-Wave Elastography in a Multistep Strategy to Detect Advanced Fibrosis in NAFLD.

BACKGROUND AND AIMS: The combination of laboratory and elastography tests allows the accurate diagnosis of advanced liver fibrosis in patients with NAFLD. In this study, we compared the diagnostic performances of a two-step strategy (laboratory tests and vibration-controlled transient elastography [VCTE] or two-dimensional shear-wave elastography with SuperSonic Imagine [2D-SWE-SSI]) and the added value of a three-step strategy (laboratory tests and two elastography methods). APPROACH AND RESULTS: From a prospective registry, we retrospectively selected 577 consecutive patients with suspicion of NAFLD who underwent laboratory tests to calculate the Fibrosis-4 (FIB-4) score, liver stiffness evaluation by VCTE (M and XL probes) and 2D-SWE-SSI, and liver biopsy. The diagnostic performances and need for liver biopsy in unclassified patients for the diagnosis of advanced fibrosis (F ≥ 3) in multistep strategies were compared. The area under the curve of FIB-4, VCTE, and 2D-SWE-SSI was 0.74, 0.82, and 0.88, respectively. Using the same thresholds, the FIB-4/2D-SWE-SSI and FIB-4/VCTE diagnostic performances were comparable (sensitivity, 71.4% and 66%; specificity, 91.4% and 91.5%; and accuracy, 83.7% and 81.4%; all P = not significant). Conversely, more patients required liver biopsy after 2D-SWE-SSI (24.6% versus 15.3%, P < 0.001). Performing a second elastography technique in patients with unreliable or gray zone (between 8 and 10 kPa) results greatly decreased the need for liver biopsy (42/577, 7.3%). The diagnostic performances (accuracy, sensitivity, and specificity) of FIB-4/2D-SWE-SSI/VCTE and FIB-4/VCTE/2D-SWE-SSI were comparable (81.1%, 71.5%, and 87.9% versus 81.3%, 69.7%, and 89.5%, respectively; all P = not significant). CONCLUSIONS: Using the same cutoff values, 2D-SWE-SSI is as accurate as VCTE for advanced liver fibrosis diagnosis in NAFLD. The three-step strategy in selected patients strongly decreased the need for liver biopsy while maintaining excellent accuracy.

Development and validation of a composite score to predict severe forms of ischemic colitis.

OBJECTIVE: To develop a simple scoring system in order to predict the risk of severe (death and/or surgery) ischemic colitis METHODS: In this retrospective study, 205 patients diagnosed with ischemic colitis in a tertiary hospital were consecutively included over a 6-year period. The study sample was sequentially divided into a training cohort (n = 103) and a validation cohort (n = 102). In the training cohort, multivariable analysis was used to identify clinical, biological, and CT variables associated with poor outcome and to build a risk scoring system. The discriminative ability of the score (sensitivity, specificity, positive predictive value, negative predictive value) was estimated in the two cohorts to externally validate the score, and a receiver operating characteristic curve was established to estimate the area under the curve of the score. Bootstrapping was used to validate the score internally. RESULTS: In the training cohort, four independent variables were associated with unfavorable outcome: hemodynamic instability (2 pts), involvement of the small bowel (1 pt), paper-thin wall pattern (3 pts), no stratified enhancement pattern (1 pt). The score was used to categorize patients into low risk (score: 0, 1), high risk (score: 2-3), and very high risk (score: 4-7) groups with sensitivity and specificity of 97% and 67%, respectively, and a good discriminating capability, with a C-statistic of 0.94. Internal and external validation showed good discrimination capability (C-statistics of 0.9 and 0.84, respectively). CONCLUSION: A simple risk score can stratify patients into three distinct prognosis groups, which can optimize patient management. CLINICAL TRIAL NUMBER: NCT04662268 KEY POINTS: • Simple scoring system predicting the risk of severe ischemic colitis • First study to include CT findings to the clinical and biological data used to determine a severity score.

Liver surface nodularity on non-contrast MRI identifies advanced fibrosis in patients with NAFLD.

OBJECTIVES: To evaluate the diagnostic performance of liver surface nodularity (LSN) for the assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: We retrospectively analysed patients with pathologically proven NAFLD who underwent liver MRI. Demographic, clinical, and laboratory data (including FIB-4 scores) were gathered. The SAF score was used to assess NAFLD. MRI-proton density fat fraction (PDFF) and LSN were determined on pre-contrast MR sequences. ROC curve analysis was performed to evaluate the diagnostic performance of MRI-LSN for the diagnosis of advanced (F3-F4) liver fibrosis. RESULTS: The final population included 142 patients. Sixty-seven (47%) patients had non-alcoholic steatohepatitis (NASH), and 52 (37%) had advanced fibrosis. The median MRI-PDFF increased with the grades of steatosis: 8.1%, 18.1%, and 31% in S1, S2, and S3 patients, respectively (p < 0.001). The area under the ROC curve (AUC) of MRI-LSN ≥ 2.50 was 0.838 (95%CI 0.767-0.894, sensitivity 67.3%, specificity 88.9%, positive and negative predictive values 77.8% and 82.5%, respectively) for the diagnosis of advanced fibrosis. Combining FIB-4 and MRI-LSN correctly classified 103/142 (73%) patients. This was validated in an external cohort of 75 patients. CONCLUSIONS: MRI-LSN has good diagnostic performance in diagnosis of advanced fibrosis in NAFLD patients. A combination of FIB-4 and MRI-LSN derived from pre-contrast MRI could be helpful to detect advanced fibrosis. KEY POINTS: • MRI-LSN ≥ 2.5 was accurate for the diagnosis of advanced hepatic fibrosis in NAFLD patients. • The combination of FIB-4 and MRI-LSN improved the detection of advanced fibrosis. • MRI-LSN can be easily derived by unenhanced MRI sequences that are routinely acquired.

Progression of AFP SCORE is a Preoperative Predictive Factor of Microvascular Invasion in Selected Patients Meeting Liver Transplantation Criteria for Hepatocellular Carcinoma.

Microvascular invasion (MVI) is one of the main prognostic factors of hepatocellular carcinoma (HCC) after liver transplantation (LT), but its occurrence is unpredictable before surgery. The alpha fetoprotein (AFP) model (composite score including size, number, AFP), currently used in France, defines the selection criteria for LT. This study's aim was to evaluate the preoperative predictive value of AFP SCORE progression on MVI and overall survival during the waiting period for LT. Data regarding LT recipients for HCC from 2007 to 2015 were retrospectively collected from a single institutional database. Among 159 collected cases, 34 patients progressed according to AFP SCORE from diagnosis until LT. MVI was shown to be an independent histopathological prognostic factor according to Cox regression and competing risk analysis in our cohort. AFP SCORE progression was the only preoperative predictive factor of MVI (OR = 10.79 [2.35-49.4]; p 0.002). The 5-year overall survival in the progression and no progression groups was 63.9% vs. 86.3%, respectively (p = 0.001). Cumulative incidence of HCC recurrence was significantly different between the progression and no progression groups (Sub-HR = 4.89 [CI 2-11.98]). In selected patients, the progression of AFP SCORE during the waiting period can be a useful preoperative tool to predict MVI.

Adverse events, short- and long-term outcomes of extra corporeal liver therapy in the intensive care unit: 16 years experience with MARS® in a single center.

BACKGROUND: Molecular Adsorbent Recirculating System (MARS®) is a non-biological artificial liver device. The benefit risk ratio between uncertain clinical effects and potential adverse events remains difficult to assess. We sought to describe adverse events related to MARS® therapy as well as biological and clinical effects. METHODS: All intensive care unit (ICU) admissions to whom MARS® therapy was prescribed from March 2005 to August 2021 were consecutively and prospectively included. The main endpoint was the incidence of adverse events related to MARS® therapy. Secondary endpoints were the biological and clinical effects of MARS® therapy. RESULTS: We reported 180 admissions treated with MARS® therapy. Among the 180 admissions, 56 (31.1%) were for acute-on-chronic liver failure, 32 (17.8%) for acute liver failure, 28 (15.5%) for post-surgery liver failure, 52 (28.9%) for pruritus and 12 (6.7%) for drug intoxication. At least one adverse event occurred in 95 (52.8%) admissions. Thrombocytopenia was the most frequent adverse event which was recorded in 55 admissions (30.6%). Overall, platelets count was 131 (± 95) × 109/L before and 106 (± 72) × 109/L after MARS® therapy (p < .001). After MARS® therapy, total bilirubin was significantly decreased in all groups (p < 0.05). Hepatic encephalopathy significantly improved in both the acute-on-chronic and in the acute liver failure group (p = 0.01). In the pruritus group, pruritus intensity score was significantly decreased after MARS® therapy (p < 0.01). CONCLUSION: In this large cohort of patients treated with MARS® therapy we report frequent adverse events. Thrombocytopenia was the most frequent adverse event. In all applications significant clinical and biological improvements were shown with MARS® therapy.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab.

PURPOSE: The objective of this study was to build and validate a radiomic signature to predict early a poor outcome using baseline and 2-month evaluation CT and to compare it to the RECIST1·1 and morphological criteria defined by changes in homogeneity and borders. METHODS: This study is an ancillary study from the PRODIGE-9 multicentre prospective study for which 491 patients with metastatic colorectal cancer (mCRC) treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab had been analysed. In 230 patients, computed texture analysis was performed on the dominant liver lesion (DLL) at baseline and 2 months after chemotherapy. RECIST1·1 evaluation was performed at 6 months. A radiomic signature (Survival PrEdiction in patients treated by FOLFIRI and bevacizumab for mCRC using contrast-enhanced CT TextuRe Analysis (SPECTRA) Score) combining the significant predictive features was built using multivariable Cox analysis in 120 patients, then locked, and validated in 110 patients. Overall survival (OS) was estimated with the Kaplan-Meier method and compared between groups with the logrank test. An external validation was performed in another cohort of 40 patients from the PRODIGE 20 Trial. RESULTS: In the training cohort, the significant predictive features for OS were: decrease in sum of the target liver lesions (STL), (adjusted hasard-ratio(aHR)=13·7, p=1·93×10-7), decrease in kurtosis (ssf=4) (aHR=1·08, p=0·001) and high baseline density of DLL, (aHR=0·98, p<0·001). Patients with a SPECTRA Score >0·02 had a lower OS in the training cohort (p<0·0001), in the validation cohort (p<0·0008) and in the external validation cohort (p=0·0027). SPECTRA Score at 2 months had the same prognostic value as RECIST at 6 months, while non-response according to RECIST1·1 at 2 months was not associated with a lower OS in the validation cohort (p=0·238). Morphological response was not associated with OS (p=0·41). CONCLUSION: A radiomic signature (combining decrease in STL, density and computed texture analysis of the DLL) at baseline and 2-month CT was able to predict OS, and identify good responders better than RECIST1.1 criteria in patients with mCRC treated by FOLFIRI and bevacizumab as a first-line treatment. This tool should now be validated by further prospective studies. TRIAL REGISTRATION: Clinicaltrial.gov identifier of the PRODIGE 9 study: NCT00952029.Clinicaltrial.gov identifier of the PRODIGE 20 study: NCT01900717.

Comparison of extracellular and hepatobiliary MR contrast agents for the diagnosis of small HCCs.

BACKGROUND & AIMS: The aim of this study was to use a head-to-head nodule comparison to compare the performance of extracellular contrast agent MRI (ECA-MRI) with that of hepatobiliary contrast agent MRI (HBA-MRI) for the non-invasive diagnosis of small hepatocellular carcinomas (HCCs). METHODS: Between August 2014 and October 2017, 171 patients with cirrhosis, each with 1 to 3 nodules measuring 1-3 cm, were enrolled across 8 centers. All patients underwent both an ECA-MRI and an HBA-MRI within a month. A non-invasive diagnosis of HCC was made when a nodule exhibited arterial phase hyper-enhancement (APHE) with washout at the portal venous phase (PVP) and/or delayed phase (DP) for ECA-MRI, or the PVP and/or HB phase (HBP) for HBA-MRI. The gold standard was defined by using a previously published composite algorithm. RESULTS: A total of 225 nodules, of which 153 were HCCs and 72 were not, were included. The sensitivites of both MRI techniques were similar. Specificity was 83.3% (95% CI 72.7-91.1) for ECA-MRI and 68.1% (95% CI 56.0-78.6) for HBA-MRI. In terms of HCC diagnosis on ECA-MRI, 138 nodules had APHE, 84 had washout at PVP, and 104 at DP; on HBA-MRI, 128 nodules had APHE, 71 had washout at PVP, and 99 at HBP. For nodules 2-3 cm in size, sensitivity and specificity were similar between the 2 approaches. For nodules 1-2 cm in size, specificity dropped to 66.1% (95% CI 52.2-78.2) for HBA-MRI vs. 85.7% (95% CI 73.8-93.6) for ECA-MRI. CONCLUSIONS: HBA-MRI specificity is lower than that of ECA-MRI for diagnosing small HCCs in patients with cirrhosis. These results raise the question of the proper use of HBA-MRI in algorithms for the non-invasive diagnosis of small HCCs. LAY SUMMARY: There are 2 magnetic resonance imaging (MRI)-based approaches available for the non-invasive diagnosis of hepatocellular carcinoma (HCC), using either extracellular or hepatobiliary contrast agents. The current results showed that the sensitivity of MRI with hepatobiliary contrast agents was similar to that with extracellular contrast agents, but the specificity was lower. Thus, hepatobiliary contrast agent-based MRI, although detailed in international guidelines, should be used with caution for the non-invasive diagnosis of HCC. CLINICAL TRIAL NUMBER: NCT00848952.

Agreement Between 2-Dimensional Shear Wave and Transient Elastography Values for Diagnosis of Advanced Chronic Liver Disease.

BACKGROUND & AIMS: Inter-platform variation in liver stiffness evaluation (LSE) could hinder dissemination and clinical implementation of new ultrasound methods. We aimed to determine whether measurements of liver stiffness by bi-dimensional shear wave elastography (2D-SWE) with a Supersonic Imagine apparatus are comparable to those made by vibration-controlled transient elastography (VCTE). METHODS: We collected data from 1219 consecutive patients with chronic liver disease who underwent LSE by VCTE and 2D-SWE (performed by blinded operators), on the same day, at a single center in France from September 2011 through June 2019. We assessed the ability of liver stiffness value distributions and 2D-SWE performances to identify patients with compensated advanced chronic liver disease (cACLD) according to the Baveno VI criteria, based on VCTE cut-off values. RESULTS: VCTE and 2D-SWE values correlated (Pearson's correlation coefficient, 0.882; P < .0001; Lin concordance coefficient, 0.846; P < .0001). The median stiffness values were 6.7 kPa with VCTE (interquartile range, 4.8-11.6 kPa) and 7.1 kPa with 2D-SWE (interquartile range, 5.4-11.1 kPa) (P = .736). 2D-SWE values were slightly higher in the low percentiles and lower in the high percentiles; the best match with VCTE values were at approximately 7-9 kPa. The area under the curve of 2D-SWE for identifying of VCTE values below 10 was 0.964 (95% CI, 0.952-0.976) and for VCTE values above 15 kPa was 0.976 (95% CI, 0.963-0.988), with Youden index-associated cut-off values of 9.5 and 13kPa and best accuracy cut-off values of 10 kPa and 14 kPa, respectively. A 2D-SWE cut-off value of 10 kPa detected VCTE values below 10k Pa with 92% sensitivity, 87% specificity, and 91% accuracy. CONCLUSIONS: Measurement of liver stiffness by VCTE or 2D-SWE produces comparable results. 2D-SWE accurately identifies patients with cACLD according to the Baveno VI criteria based on VCTE cut-off values. A 10 kPa 2D-SWE cut-off value can be used to rule out cACLD.

Study protocol of the HYPER-LIV01 trial: a multicenter phase II, prospective and randomized study comparing simultaneous portal and hepatic vein embolization to portal vein embolization for hypertrophy of the future liver remnant before major hepatectomy for colo-rectal liver metastases.

BACKGROUND: In patients undergoing major liver resection, portal vein embolization (PVE) has been widely used to induce hypertrophy of the non-embolized liver in order to prevent post-hepatectomy liver failure. PVE is a safe and effective procedure, but does not always lead to sufficient hypertrophy of the future liver remnant (FLR). Hepatic vein(s) embolization has been proposed to improve FLR regeneration when insufficient after PVE. The sequential right hepatic vein embolization (HVE) after right PVE demonstrated an incremental effect on the FLR but it implies two different procedures with no time gain as compared to PVE alone. We have developed the so-called liver venous deprivation (LVD), a combination of PVE and HVE during the same intervention, to optimize the phase of liver preparation before surgery. The main objective of this randomized phase II trial is to compare the percentage of change in FLR volume at 3 weeks after LVD or PVE. METHODS: Patients eligible to this multicenter prospective randomized phase II study are subjects aged from 18 years old suffering from colo-rectal liver metastases considered as resectable and with non-cirrhotic liver parenchyma. The primary objective is the percentage of change in FLR volume at 3 weeks after LVD or PVE using MRI or CT-Scan. Secondary objectives are assessment of tolerance, post-operative morbidity and mortality, post-hepatectomy liver failure, rate of non-respectability due to insufficient FLR or tumor progression, per-operative difficulties, blood loss, R0 resection rate, post-operative liver volume and overall survival. Objectives of translational research studies are evaluation of pre- and post-operative liver function and determination of biomarkers predictive of liver hypertrophy. Sixty-four patients will be included (randomization ratio 1:1) to detect a difference of 12% at 21 days in FLR volumes between PVE and LVD. DISCUSSION: Adding HVE to PVE during the same procedure is an innovative and promising approach that may lead to a rapid and major increase in volume and function of the FLR, thereby increasing the rate of resectable patients and limiting the risk of patient's drop-out. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov on 15th February 2019 (NCT03841305).

Quantification of liver fat content in liver and primary liver lesions using triple-echo-gradient-echo MRI.

OBJECTIVES: To quantify and compare the fat fraction of background liver and primary liver lesions using a triple-echo-gradient-echo sequence. M&M: This IRB-approved study included 128 consecutive patients who underwent a liver MRI for lesion characterization. Fat fraction from the whole lesion volume and the normal liver parenchyma were computed from triple-echo (consecutive in-phase, opposed-phase, in-phase echo times) sequence. RESULTS: Forty-seven hepatocellular carcinoma (HCCs), 25 hepatocellular adenomas (HCAs), and 56 focal nodular hyperplasia (FNH) were included. The mean intralesional fat fraction for various lesions was 7.1% (range, 0.5-23.6; SD, 5.6) for HCAs, 5.7% (range, 0.8-14; SD, 2.9) for HCCs, and 2.3% (range, 0.8-10.3; SD, 1.9) for FNHs (p = 0.6 for HCCs vs HCA, p < 0.001 for FNH vs HCCs or HCA). A fat fraction threshold of 2.7% enabled distinction between HCA and FNH with a sensitivity of 80% and a specificity of 77%. The mean normal liver parenchyma fat fraction was lower than the intralesional fat fraction in the HCC group (p = 0.04) and higher in the FNH group (p = 0.001), but not significantly different in the HCA group (p = 0.51). CONCLUSION: Triple-echo-gradient-echo is a feasible technique to quantify fat fraction of background liver and primary liver lesions. Intralesional fat fraction obtained from lesion whole volume is greater for HCCs and HCA compared to FNH. When trying to distinguish FNH and HCA, an intralesional fat fraction < 2.7% may orient toward the diagnosis of FNH. KEY POINTS: • Triple-echo technique is feasible to quantify intralesional fat fraction of primary liver lesions. • Whole volume intralesional fat fraction is greater for HCCs and HCA compared to FNH. • An intralesional fat fraction < 2.7% may orient toward the diagnosis of FNH.

Learning curve of liver stiffness measurement using a new hybrid machine composed of transient elastography interfaced with ultrasound.

OBJECTIVES: To assess the learning curve for performing reliable liver stiffness measurements using a new hybrid machine composed of transient elastography (TE) interfaced with an ultrasound device for radiographers and radiologists with different levels of expertise in ultrasound imaging. METHODS: Ten novice operators who had never performed TE measurements were prospectively evaluated from April to October 2018: senior radiologists, young radiologists, fellows, radiographers, and residents, with different levels of experience in abdominal ultrasound imaging. All operators had a short theoretical training followed by a training session under supervision in three patients. Then, each operator had to perform TE in 50 consecutive patients with chronic liver disease, using beforehand ultrasound examination to select measurement area in the right liver lobe, and if needed, the XL probe. Percentages of failures and reliable measurements were compared. RESULTS: The rates of failures of measurements, poorly reliable, reliable, and very reliable results, were of 4.2% (21/500), 2.4% (12/500), 47.6% (238/500), and 45.8% (229/500), respectively. The rates of reliable plus very reliable results were excellent, ranging from 91 to 96% among all the subgroups. The rates of very reliable, reliable, and unreliable results did not differ between operator subgroups and especially between junior radiologists, senior radiologists, and radiographers. No breaking point was observed in the interquartile range/median values over time. CONCLUSION: TE interfaced with ultrasound in this hybrid machine presents no learning curve effect. After a short initial training session, a novice observer is able to perform high rates of reliable and very reliable TE measurements. KEY POINTS: • When performing liver stiffness measurements using a new hybrid machine composed of transient elastography interfaced with ultrasound, the rate of failures of measurements is very low, below 5%. • After a short training session and using ultrasound planning, a novice operator, whatever its expertise in ultrasound imaging, is capable of performing high rates of reliable and very reliable measurements. • No learning curve is needed for performing reliable liver stiffness measurements using this new hybrid machine.

Improving the Safety of Major Resection for Hepatobiliary Malignancy: Portal Vein Embolization and Recent Innovations in Liver Regeneration Strategies.

PURPOSE OF REVIEW: For three decades, portal vein embolization (PVE) has been the "gold-standard" strategy to hypertrophy the anticipated future liver remnant (FLR) in advance of major hepatectomy. During this time, CT volumetry was the most common method to preoperatively assess FLR quality and function and used to determine which patients are appropriate surgical candidates. This review provides the most up-to-date methods for preoperatively assessing the anticipated FLR and summarizes data from the currently available strategies used to induce FLR hypertrophy before surgery for hepatobiliary malignancy. RECENT FINDINGS: Functional and physiological imaging is increasingly replacing standard CT volumetry as the method of choice for preoperative FLR assessment. PVE, associating liver partition and portal vein ligation, radiation lobectomy, and liver venous deprivation are all currently available techniques to hypertrophy the FLR. Each strategy has pros and cons based on tumor type, extent of resection, presence or absence of underlying liver disease, age, performance status, complication rates, and other factors. Numerous strategies can lead to FLR hypertrophy and improve the safety of major hepatectomy. Which is best has yet to be determined.

Intra-arterial idarubicin_lipiodol without embolization can provide prolonged complete response in hepatocellular carcinoma: A case report.

Hepatocellular carcinoma is the fourth leading cause of cancer death. For unresectable intermediate-stage hepatocellular carcinoma, the standard treatment is transarterial chemoembolization. To date, the overall survival at three years remains low, and there is currently no consensus about the best anticancer agent and optimal treatment regimen. We report the case of a hepatocellular carcinoma patient with a vascular contraindication to embolization who achieved a complete response after four intra-arterial infusions of idarubicin emulsified with lipiodol. The patient maintained his response over a three-year period without any hepatocellular carcinoma treatment, demonstrating the major role of the anticancer agent in the efficacy of transarterial therapies for intermediate-stage hepatocellular carcinoma.

Idarubicin-loaded Beads for Chemoembolization of Hepatocellular Carcinoma: The IDASPHERE II Single-Arm Phase II Trial.

Background A prior in vitro study showed that idarubicin was the most cytotoxic agent for hepatocellular carcinoma (HCC) cell lines. Idarubicin-loaded beads for transarterial chemoembolization (TACE) were previously evaluated for the appropriate dose in a phase I dose-escalation study. Purpose To evaluate objective response rate (ORR), safety, and survival after TACE by using idarubicin-loaded beads for unresectable HCC. Materials and Methods This prospective single-arm phase II study was conducted between January 2015 and January 2017. Participants with unresectable HCC were included in the trial and underwent TACE with idarubicin-eluting beads. The primary end point was 6-month ORR assessed with independent central review by using modified Response Evaluation Criteria in Solid Tumors. Secondary end points were best ORR during the first 6 months, overall survival, progression-free survival, time to progression, and safety. A two-stage Fleming statistical design was used. Results Forty-six study participants (mean age, 71.2 years ± 10.2; six women and 40 men) were included; 44 participants underwent at least one TACE session. The 6-month ORR was 52% (23 of 44). The best ORR achieved was 68% (30 of 44). Fourteen of 44 (32%) participants underwent a curative treatment after TACE. Median progression-free survival, time to progression, and overall survival were 6.6 months, 9.5 months, and 18.6 months, respectively. TACE was discontinued for toxicity in four of 44 (9%) participants. The most frequent grade 3-4 adverse events were elevated aspartate aminotransferase (14 of 44, 32%), elevated γ-glutamyl transpeptidase (eight of 44, 18%), hyperbilirubinemia (seven of 44, 16%), elevated alanine aminotransferase (seven of 44, 16%), and pain (seven of 44, 16%). Conclusion Idarubicin-eluting beads showed a good safety profile and promising objective response rate and time to progression when used as part of a transarterial chemoembolization regimen for unresectable hepatocellular carcinoma. © RSNA, 2019 See also the editorial by Padia in this issue.

Macrotrabecular-massive hepatocellular carcinoma: A distinctive histological subtype with clinical relevance.

We recently identified a histological subtype of hepatocellular carcinoma (HCC), designated as "macrotrabecular-massive" (MTM-HCC) and associated with specific molecular features. In order to assess the clinical relevance of this variant, we investigated its prognostic value in two large series of patients with HCC treated by either surgical resection or radiofrequency ablation (RFA). We retrospectively included 237 HCC surgical samples and 284 HCC liver biopsies from patients treated by surgical resection and RFA, respectively. Histological slides were reviewed by pathologists specialized in liver disease, and the MTM-HCC subtype was defined by the presence of a predominant (>50%) macrotrabecular architecture (more than six cells thick). The main clinical and biological features were recorded at baseline. Clinical endpoints were early and overall recurrence. The MTM-HCC subtype was identified in 12% of the whole cohort (16% of surgically resected samples, 8.5% of liver biopsy samples). It was associated at baseline with known poor prognostic factors (tumor size, alpha-fetoprotein level, satellite nodules, and vascular invasion). Multivariate analysis showed that MTM-HCC subtype was an independent predictor of early and overall recurrence (surgical series: hazard ratio, 3.03; 95% confidence interval, 1.38-6.65; P = 0.006; and 2.76; 1.63-4.67; P < 0.001; RFA series: 2.37; 1.36-4.13; P = 0.002; and 2.19; 1.35-3.54; P = 0.001, respectively). Its prognostic value was retained even after patient stratification according to common clinical, biological, and pathological features of aggressiveness. No other baseline parameter was independently associated with recurrence in the RFA series. CONCLUSION: The MTM-HCC subtype, reliably observed in 12% of patients eligible for curative treatment, represents an aggressive form of HCC that may require more specific therapeutic strategies. (Hepatology 2018;68:103-112).