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.

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis.

BACKGROUND: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. METHODS: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs ≥20 kPa; FIB-4: <1·3 vs 1·3 to ≤2·67 vs >2·67; NFS: <-1·455 vs -1·455 to ≤0·676 vs >0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226. FINDINGS: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62-0·81) for histology, 0·76 (0·70-0·83) for LSM-VCTE, 0·74 (0·64-0·82) for FIB-4, and 0·70 (0·63-0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression. INTERPRETATION: Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases. FUNDING: Innovative Medicines Initiative 2.

Large, multifocal or portal vein-invading hepatocellular carcinoma (HCC) downstaged by Y90 using personalized dosimetry: safety, pathological results and outcomes after surgery.

Background: Transarterial radioembolization (TARE) has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas (HCCs) with high rates of complete pathological necrosis (CPN) on liver explants. In patients with portal vein tumoral thrombus (PVTT), multifocal or large tumors, TARE has mainly a palliative role and surgery remains controversial in this poor-prognosis population. Personalized dosimetry recently proved to outperform standard dosimetry used in prior negative Y90 randomized-controlled trials. Methods: In this retrospective study, we evaluated safety, radiological and pathological response and outcomes in HCC patients with PVTT, multifocal or large tumors, who underwent surgery after downstaging using TARE with Y90-loaded glass microspheres with personalized dosimetry. Results: Between December 2015 and October 2021, 18 unresectable patients (14/18 with PVTT) had surgery (16 resections, 2 liver transplantations) 6.2 months (range, 2-14.6 months) after a single Y90 treatment. No 90-day mortality was reported. Objective modified response criteria in solid tumors (mRECIST) response were noted in all but one patient. Complete and extensive (50-99%) necrosis was observed in 36% and 45% of tumors, respectively. The post-treatment tumor-absorbed dose significantly differed depending on the extent of pathological necrosis (P=0.045). Median overall survival and progression-free survival (PFS) were respectively of 61.8 months [95% CI: 31.4 months-not reached (NR)] and 49.3 months (95% CI: 14 months-NR). PFS was longer in patients with complete imaging response [median NR (none recurred or died) vs. 21.5 months (95% CI: 10.1 months-NR), P<0.001] and in those with complete pathological response [median NR vs. 22.5 months (95% CI: 10.1 months-NR), P<0.001]. Conclusions: Y90 TARE using personalized dosimetry can provide high rates of imaging and pathological response in patients with PVTT, large or multifocal HCC. Subsequent surgery is safe and leads to outcomes far exceeding expectations in an otherwise poor prognosis population with no chance for cure. Trial Registration: Clinical trial number: NCT05045573.

Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes.

BACKGROUND AND AIMS: We evaluated the diagnostic accuracy of simple, noninvasive tests (NITs) in NAFLD patients with type 2 diabetes (T2D). METHODS AND RESULTS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score (NFS), aspartate aminotransferase-to-platelet ratio index, liver stiffness measurement (LSM) by vibration-controlled transient elastography, and AGILE 3+. The target conditions were advanced fibrosis, NASH, and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of noninvasive tests. individually or in sequential combination, was assessed by area under the receiver operating characteristic curve and by decision curve analysis. Comparison with 2278 NAFLD patients without T2D was also made. In NAFLD with T2D LSM and AGILE 3+ outperformed, both NFS and FIB-4 for advanced fibrosis (area under the receiver operating characteristic curve:LSM 0.82, AGILE 3+ 0.82, NFS 0.72, FIB-4 0.75, aspartate aminotransferase-to-platelet ratio index 0.68; p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%. The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40%-60% in necessary LSM tests. Decision curve analysis showed that all scores had a modest net benefit for ruling out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH (area under the receiver operating characteristic curve:LSM 0.79, AGILE 3+ 0.77, NFS 0.71, FIB-4 0.71; p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were suboptimal for diagnosing NASH. CONCLUSIONS: LSM and AGILE 3+ individually or in low availability settings in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.

Life expectancy of patients with hepatocellular carcinoma according to the upfront treatment: A nationwide analysis.

PURPOSE: The purpose of this study was to update the life expectancy of patients with hepatocellular carcinoma (HCC) in an exhaustive nationwide population according to the upfront treatment performed. MATERIALS AND METHODS: From the French Program for the Medicalization of Information System database, all patients older than 18 years diagnosed with a de novo HCC from January 2011 to December 2018 were retrospectively selected. Five-year survival rates (95% confidence intervals [CI]) were computed according to the first surgical or interventional radiology procedures performed. RESULTS: A total of 63,996 patients (80% men) with a median age of 68 years (Q1, Q3: 61, 77) were selected, including 24,007 patients who underwent at least one procedure (5-year survival of 45.5%; (95% CI: 44.8-46.2), and 39,989 with none (5-year survival, 9.6%; (95% CI: 9.3-10.0). Only 20.5% (13,101/63,996) of patients could undergo an upfront curative procedure. Liver transplantation achieved the best outcome, whether performed upfront (n = 791; 5-year survival, 79.0% [95% CI: 76.1-82.1]) or during subsequent steps (n = 2217; 5-year survival 80.9% [95% CI: 79.2-82.7]). Tumor ablation (n = 5306), open resection (n = 5171), and minimally-invasive resection (n = 1833) achieved 5-year survival rates of 53.8% (95% CI: 52.3-55.4), 54.1% (95% CI: 52.6-55.6), and 66.2% (95% CI: 63.7-68.7), respectively, with more patients with cirrhosis and subsequent procedures in the tumor ablation group. Patients with upfront transarterial (chemo)embolization (n = 10,247) and selective internal radiation therapy (n = 659) had 5-year survival rates of 31.3% (95% CI: 30.3-32.4) and 18.5% (95% CI: 15.2-22.5). CONCLUSION: While HCC remains mostly diagnosed at an advanced stage associated with a poor prognosis, all the curative options provide 5-year survival rates above 50%.

Imaging of Pancreatic Ductal Adenocarcinoma: An Update on Recent Advances.

Pancreatic ductal carcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. Computed tomography (CT) remains the primary imaging modality for diagnosis of PDAC. However, CT has limitations for early pancreatic tumor detection and tumor characterization so that it is currently challenged by magnetic resonance imaging. More recently, a particular attention has been given to radiomics for the characterization of pancreatic lesions using extraction and analysis of quantitative imaging features. In addition, radiomics has currently many applications that are developed in conjunction with artificial intelligence (AI) with the aim of better characterizing pancreatic lesions and providing a more precise assessment of tumor burden. This review article sums up recent advances in imaging of PDAC in the field of image/data acquisition, tumor detection, tumor characterization, treatment response evaluation, and preoperative planning. In addition, current applications of radiomics and AI in the field of PDAC are discussed.

Inter-platform Variability of Liver Elastography: Pairwise Comparisons of Four Devices.

This study was aimed at determining whether liver stiffness measurements by 2-D shear wave elastography using GE's (2D-SWE-GE) and Canon's (2D-SWE-Canon) newest apparatus and vibration-controlled transient elastography (VCTE) share the same distribution of values compared with Hologic Supersonic Imagine (2D-SWE-SSI). In participants with chronic liver disease recruited in two university centers from August 2020 to February 2021, liver stiffness was measured the same day by the same operator with 2D-SWE-SSI plus one of the following devices: 2D-SWE-GE (n = 314), 2D-SWE-Canon (n = 311), and VCTE-M probe (n = 812). VCTE-M and 2D-SWE-SSI values shared the highest correlation and concordance coefficients (0.933 and 0.920, respectively) and a coefficient of variation below 20%, whatever the range of values. 2D-SWE-GE had the lowest variations, with 2D-SWE-SSI values below 13 kPa. However, both 2D-SWE-GE and 2D-SWE-Canon exhibited a frank underestimation of the high percentiles' 2D-SWE-SSI values with coefficients of variation of -21.7% and -25.8% from 13- to 17-kPa values, and -44.3% and -32.4% from 17-kPa values, respectively. In conclusion, knowledge of the vendor-specific distribution of values is mandatory for interpreting results obtained with different machines. If all four techniques behave closely in low values allowing excluding advanced chronic liver diseases in larger populations, discrepancies are observed in high percentile values.

Non-transplantable recurrence after percutaneous thermal ablation of ≤3-cm HCC: Predictors and implications for treatment allocation.

Percutaneous thermal ablation (PTA), resection, and liver transplantation are the standard curative options for hepatocellular carcinoma (HCC). Liver transplantation yields the best long-term outcomes but is limited by graft shortage. Thus, patients with ≤3-cm HCC are primarily treated by PTA even though recurrence is frequent and may occur outside transplant criteria. Data on non-transplantable recurrence (NTR) following PTA are lacking, however. We therefore investigated the incidence and predictors of NTR among 213 potentially transplantable patients (cirrhosis, 93%; Child-Pugh A, 98.6%; alcohol-related disease, 62%) with ≤3-cm HCC(s) treated by PTA, to stratify them according to their NTR risk and to improve treatment allocation. During follow-up (median: 41.2 months), NTR occurred in 18.3% (alpha-fetoprotein [AFP] model) and 23% (Milan) patients. NTR prediction with competing-risk analysis and internal validation revealed AFP > 100 ng/ml (subdistribution hazard ratio: 7.28; p < 0.001) and prior HCC (subdistribution hazard ratio: 3.77; p = 0.002) as independent predictors (Harrell's C: 0.76). Based on this model using the AFP score (equally predictive within Milan criteria), patients were stratified into three NTR risk categories: HCC-naïve with AFP < 100 ng/ml (low risk, n = 108 of 213), non-HCC naïve with AFP < 100 ng/ml (intermediate risk, n = 92 of 213), AFP ≥ 100 ng/ml (high risk, n = 13 of 213), among whom 9.3% (3.7% [Milan]), 22.8% (25% [Milan]), and 61.5% (38/5% [Milan]) presented NTR (p < 0.001). Median recurrence-free survival was 4.6, 14.5, and 43.4 months, respectively, in high-risk, intermediate-risk, and low-risk categories (p < 0.001). Median overall survival, which was 19.1 months in high-risk patients, was not reached otherwise (p < 0.001). Conclusion: Overall, PTA of ≤3-cm HCC incurs a low NTR risk. Simple and noninvasive predictors (HCC naivety, AFP) accurately stratified patients' risk of NTR, and should help to improve treatment allocation. Patients with AFP ≥ 100 ng/ml have a high risk of NTR, poor recurrence-free survival, and overall survival. Further studies evaluating preemptive transplantation or adjuvant/neoadjuvant strategies are highly needed in this small patient subset.

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.

Software-based assessment of tumor margins after percutaneous thermal ablation of liver tumors: A systematic review.

PURPOSE: The purpose of this study was to make a systematic review of clinical studies evaluating software-based tumor margin assessment after percutaneous thermoablation (PTA) of liver tumors. MATERIALS AND METHODS: A systematic literature search was performed through Pubmed/MEDLINE, Embase and the Cochrane Library. Original studies published in English that reported on software-based assessment of ablation margins (AM) following PTA of liver tumors were selected. Studies were analyzed with respect to design, number of patients and tumors, tumor type, PTA technique, tumor size, target registration error, study outcome(s) (subtypes: feasibility, comparative, clinical impact, predictive or survival), and follow-up period. RESULTS: Twenty-nine articles (one multi-center and two prospective studies) were included. The majority were feasibility (26/29, 89.7%) or predictive (23/29, 79.3%) studies. AM was a risk factor of local tumor progression (LTP) in 25 studies (25/29, 86.2%). In nine studies (9/29, 31%) visual assessment overestimated AM compared with software-aided assessment. LTP occurred at the location of the thinnest margin in nine studies (9/29, 31%). Time for registration and analysis was heterogeneously reported, ranging between 5-30 min. Mean target registration error was reported in seven studies (7/29, 24.1%) at 1.62 mm (range: 1.20-2.23 mm). Inter-operator reproducibility was high (kappa range: 0.686-1). Ascites, liver deformation and inconspicuous tumor were major factors of co-registration error. CONCLUSION: Available studies present a low level of evidence overall, since most of them are feasibility, retrospective and single-center studies.

Reliability Criteria of Two-Dimensional Shear Wave Elastography: Analysis of 4277 Measurements in 788 Patients.

BACKGROUND & AIMS: Two-dimensional shear wave elastography (2D-SWE) is an accurate method for the non-invasive evaluation of liver fibrosis. We aimed to determine the reliability criteria and the number of necessary reliable measurements for 2D-SWE. METHODS: 788 patients with chronic liver disease underwent liver biopsy and 2D-SWE examination in three centers. The 4277 2D-SWE measurements performed were 2:1 randomly divided into derivation (n = 2851) and validation (n = 1426) sets. Reliability criteria for a 2D-SWE measurement were defined in the derivation set from the intrinsic characteristics given by the device (mean liver stiffness, standard deviation, diameter of the region of interest), with further evaluation in the validation set. RESULTS: In the whole population of 4277 measurements, AUROC for bridging fibrosis was 0.825 ± 0.006 and AUROC for cirrhosis was 0.880 ± 0.006. Mean stiffness and coefficient of variation (CV) were independent predictors of bridging fibrosis or cirrhosis. From these two parameters, new criteria were derived to define a reliable 2D-SWE measurement: stiffness <8.8 kPa, or stiffness between 8.8-11.9 kPa with CV <0.25, or stiffness ≥12.0 kPa with CV <0.10. In the validation set, AUROC for bridging fibrosis was 0.830 ± 0.013 in reliable measurements vs 0.667 ± 0.031 in unreliable measurements (P < .001). AUROC for cirrhosis was 0.918±0.014 vs 0.714 ± 0.027, respectively (P < .001). The best diagnostic accuracy for a 2D-SWE examination was achieved from three reliable measurements. CONCLUSIONS: Reliability of a 2D-SWE measurement relies on the coefficient of variation and the liver stiffness level. A 2D-SWE examination should include three reliable measurements according to our new criteria.

Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease.

OBJECTIVE: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients. DESIGN: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation. RESULTS: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM. CONCLUSION: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.

Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis.

OBJECTIVE: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. DESIGN: Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. RESULTS: Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy. CONCLUSION: Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.

Non-invasive diagnosis and follow-up of portal hypertension.

Compensated advanced chronic liver disease (cACLD) describes the spectrum of advanced fibrosis/cirrhosis in asymptomatic patients at risk of developing clinically significant portal hypertension (CSPH, defined by a hepatic venous pressure gradient (HVPG) ≥10 mmHg). Patients with cACLD are at high risk of liver-related morbidity and mortality. In patients at risk of chronic liver disease, cACLD is strongly suggested by a liver stiffness (LSM) value >15 kPa or clinical/biological/radiological signs of portal hypertension, and ruled out by LSM <10 kPa, or Fibrotest® ≤0.58, or Fibrometer® ≤0.786. Patients with chronic liver disease (excluding vascular diseases) with a LSM <10 kPa are at low risk of developing portal hypertension complications. The presence of CSPH can be strongly suspected when LSM is ≥20 kPa. In a patient without clinical, endoscopic or radiological features of portal hypertension, measurement of the HVPG is recommended before major liver or intra-abdominal surgery, before extra-hepatic transplantation and in patients with unexplained ascites. Endoscopic screening for oesophageal varices can be avoided in patients with LSM <20 kPa and a platelet count >150 G/L (favourable Baveno VI criteria) at the time of diagnosis. There is no non-invasive method alternative for oeso-gastroduodenal endoscopy in patients with unfavourable Baveno criteria (liver stiffness ≥20 kPa or platelet count ≤50 G/l). Platelet count and liver stiffness measurements must be performed once a year in patients with cACLD with favourable Baveno VI criteria at the time of diagnosis. A screening oeso-gastroduodenal endoscopy is recommended if Baveno VI criteria become unfavourable.

99mTc-mebrofenin hepatobiliary scintigraphy and volume metrics before liver preparation: correlations and discrepancies in non-cirrhotic patients.

BACKGROUND: Accurate identification of insufficient future liver remnant (FLR) is required to select patients for liver preparation and limit the risk of post-hepatectomy liver failure (PHLF). The objective of this study was to investigate the correlations and discrepancies between the most-commonly used FLR volume metrics and 99mTc-mebrofenin hepatobiliary scintigraphy (HBS). METHODS: In 101 non-cirrhotic patients who underwent HBS before major hepatectomy, we retrospectively analyzed the correlations and discrepancies between FLR function and FLR volume metrics: actual percentage (FLRV%), standardized to body surface area (FLRV%BSA) and weight (FLRV%weight), and FLR to body weight ratio (FLRV-BWR). RESULTS: Among 67 patients with FLR function ≥2.69%/min/m2, PHLF was observed in none and 13 patients according to respectively 50-50 and ISGLS criteria. FLRV%, FLRV%BSA, FLRV%weight and FLRV-BWR significantly correlated with FLR function (P<0.001), with Spearman's correlation coefficients of 0.680, 0.704, 0.698, and 0.711, respectively. No difference was observed between the areas under the curve of FLRV%, FLRV%BSA, FLRV%weight and FLR-BWR (all P=ns). Overall, the percentages of patients misclassified by FLRV%, FLRV%BSA, FLRV%weight (thresholds: 30%) and FLR-BWR (threshold: 0.5) versus FLR function (threshold: 2.69%/min/m2) were 23.8% (95% CI: 15.9-33.3%), 18.8% (95% CI: 11.7-27.8%), 17.8% (95% CI: 11-26.7%), and 31.7% (95% CI: 22.8-41.7%), respectively. FLR volume metrics wrongly classified 1-13.9% of patients with sufficient FLR function (i.e., ≥2.69%/min/m2), and 9.9-30.7% of patients with insufficient FLR function. FLRV-BWR was the most and the least reliable measure to identify patients with sufficient and insufficient FLR function, respectively. CONCLUSIONS: Despite significant correlations, the discrepancy rates between FLR volume and function metrics speaks in favor of implementing 99mTc-mebrofenin HBS in the work-up before liver preparation.

Hepatobiliary Scintigraphy and Glass 90Y Radioembolization with Personalized Dosimetry: Dynamic Changes in Treated and Nontreated Liver.

BACKGROUND: The functional changes that occur over time in the liver following 90Y-radioembolization (RE) using personalized dosimetry (PD) remain to be investigated. METHODS: November 2016-October 2019: we retrospectively included hepatocellular carcinoma (HCC) patients treated by 90Y-glass RE using PD, who underwent hepatobiliary scintigraphy (HBS) at baseline and at 15 days, 1, 2, 3, and 6 months after RE. RESULTS: There were 16 patients with unilobar disease (100%) included, and 64 HBS were performed. Whole liver function significantly decreased over time. The loss was maximal at 2 weeks: -32% (p = 0.002) and remained below baseline at 1 (-15%; p = 0.002), 2 (-25%; p < 0.001), and 3 months (-16%; p = 0.027). No radioembolization-induced liver disease was observed. Treated liver function strongly decreased to reach -64% (p < 0.001) at 2 months. Nontreated liver function decreased at 2 weeks (-21%; p = 0.027) and remained below baseline before reaching +20% (p = 0.002) and +59% (p < 0.001) at 3 and 6 months, respectively. Volumetric and functional changes exhibited parallel evolutions in the treated livers (p = 0.01) but independent evolutions in the nontreated livers (p = 0.08). CONCLUSION: RE using PD induces significant regional changes in liver function over time. As early as 15 days following RE, both the treated and nontreated livers showed a decreased function. Nontreated liver function recovered after 3 months and greatly increased afterwards.

Uni-, Bi- or Trifocal Hepatocellular Carcinoma in Western Patients: Recurrence and Survival after Percutaneous Thermal Ablation.

Multifocality is usually reported as a pejorative factor after percutaneous thermal ablation (PTA) of HCC but little is known in Western series. Recurrence and survival were extracted from a prospective database of all patients who underwent PTA for ≤3 cm HCC. From January 2015 to April 2020, we analyzed 281 patients with unifocal (n = 216), bifocal (n = 46) and trifocal (n = 16) HCC. PTA of bi- and trifocal HCC resulted in a high risk of very early (<6 months) distant recurrence (38.8% and 50%, respectively). Median RFS was 23.3 months (95% CI:18.6-30.4), 7.7 months (95% CI:5.1-11.43, p = 0.002) and 5.2 months (95% CI:3-12.3, p = 0.015), respectively, for uni-, bi- and trifocal HCC groups. In a multivariate analysis, both bifocal (HR = 2.46, p < 0.001) and trifocal (HR = 2.70, p = 0.021) vs. unifocal HCC independently predicted shorter RFS. Median OS in trifocal HCC group was 30.3 months (95 CI:19.3-not reached). Trifocal vs. unifocal HCC independently predicted shorter OS (HR = 3.30, p = 0.008), whereas bifocal vs. unifocal HCC did not (p = 0.27). Naïve patient (HR = 0.42, p = 0.007), AFP > 100 ng/mL (HR = 3.03, p = 0.008), MELD > 9 (HR = 2.84, p = 0.001) and steatotic HCC (HR = 0.12, p = 0.038) were also independent predictors of OS. In conclusion, multifocal HCCs in a Western population have a dramatically increased risk of distant recurrence. OS after PTA of trifocal HCC is significantly below what was expected after a curative treatment.

Small Steatotic HCC: A Radiological Variant Associated With Improved Outcome After Ablation.

Percutaneous thermal ablation is a validated treatment option for small hepatocellular carcinoma (HCC). Steatotic HCC can be reliably detected by magnetic resonance imaging. To determine the clinical relevance of this radiological variant, we included 235 patients (cirrhosis in 92.3%, classified Child-Pugh A in 97%) from a prospective database on percutaneous thermal ablation for <3 cm HCC. Among these patients, 52 (22.1%) had at least one steatotic HCC nodule. Nonalcoholic steatohepatitis was more frequent in patients with than without steatotic HCC (P = 0.057), whereas body mass index, diabetes mellitus, liver steatosis, and liver fat content did not differ between groups. Liver disease was less advanced in patients with than without steatotic HCC: lower total bilirubin ( - 2.1 µmol/L; P = 0.035), higher albumin (+0.8 g/L; P = 0.035), and lower Model for End-Stage Liver Disease score (-0.8; P = 0.014). Tumor phenotype was less aggressive in patients with steatotic HCC: lower alpha-fetoprotein (AFP) concentration (P = 0.019), less frequent AFP > 100 ng/mL (P = 0.045), and multifocality (P = 0.015). During the follow-up (median: 28.3 months), overall mortality (3.8% vs. 23.5%; P = 0.001) and HCC-specific mortality (0.0% vs. 14.2%; P = 0.002) rates were lower in patients with steatotic HCC. Early (<2 years) recurrence was also less frequent (32.7% vs. 49.2%; P = 0.041). The mean time to intrahepatic distant recurrence (16.4 vs. 9 months, P = 0.006) and the median time to recurrence and recurrence-free survival (32.4 vs. 18.6 months, P = 0.024 and 30.4 vs. 16.4 months, P = 0.018) were longer in patients with steatotic versus nonsteatotic HCC. The 3-year overall survival was 94.4% and 70.9% in steatotic and nonsteatotic HCC (P = 0.008). In multivariate analysis, steatotic HCC (hazard ratio = 0.12; P = 0.039) and AFP (HR=1.002; P < 0.001) independently predicted overall survival. Conclusion: Small steatotic HCC detected by magnetic resonance imaging is associated with a less aggressive tumor phenotype. In patients with such radiological variant, percutaneous thermal ablation results in improved outcome.

Artificial intelligence: a critical review of current applications in pancreatic imaging.

The applications of artificial intelligence (AI), including machine learning and deep learning, in the field of pancreatic disease imaging are rapidly expanding. AI can be used for the detection of pancreatic ductal adenocarcinoma and other pancreatic tumors but also for pancreatic lesion characterization. In this review, the basic of radiomics, recent developments and current results of AI in the field of pancreatic tumors are presented. Limitations and future perspectives of AI are discussed.