Severe hepatic steatosis promotes increased liver stiffness in the early stages of metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: The predictors of progression from steatosis to more advanced stages of metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We evaluated the association between the quantity of hepatic steatosis and longitudinal changes in liver stiffness measurements (LSMs) using magnetic resonance elastography (MRE) in patients with MASLD. METHODS: We retrospectively analysed patients with MASLD who underwent at least two serial MRE and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) examinations at least 1 year apart. Fine-Gray competitive proportional hazard regression was used to identify LSM progression and regression factors. RESULTS: A total of 471 patients were enrolled. Factors linked to LSM progression were steatosis grade 3 (MRI-PDFF ≥17.1%, adjusted hazard ratio [aHR] 2.597; 95% confidence interval [CI] 1.483-4.547) and albumin-bilirubin grade 2 or 3 (aHR 2.790; 95% CI 1.284-6.091), while the only factor linked to LSM regression was % decrease rate of MRI-PDFF ≥5% (aHR 2.781; 95% CI 1.584-4.883). Steatosis grade 3 correlated with a higher incidence rate of LSM progression than steatosis grade 1 (MRI-PDFF <11.3%) in patients with LSM stage 0 (<2.5 kilopascal [kPa]), and a % annual decrease rate of MRI-PDFF ≥5% correlated with a higher incidence rate of LSM regression than that of MRI-PDFF >-5% and <5% in patients with LSM stage 1 or 2-4 (≥2.5 kPa). CONCLUSIONS: Severe hepatic steatosis was linked to significant LSM progression in patients with MASLD and low LSM (<2.5 kPa).

iATT liver fat quantification for steatosis grading by referring to MRI proton density fat fraction: a multicenter study.

BACKGROUND: Several preliminary reports have suggested the utility of ultrasound attenuation coefficient measurements based on B-mode ultrasound, such as iATT, for diagnosing steatotic liver disease. Nonetheless, evidence supporting such utility is lacking. This prospective study aimed to investigate whether iATT is highly concordant with magnetic resonance imaging (MRI)-based proton density fat fraction (MRI-PDFF) and could well distinguish between steatosis grades. METHODS: A cohort of 846 individuals underwent both iATT and MRI-PDFF assessments. Steatosis grade was defined as grade 0 with MRI-PDFF < 5.2%, grade 1 with 5.2% MRI-PDFF < 11.3%, grade 2 with 11.3% MRI-PDFF < 17.1%, and grade 3 with MRI-PDFF of 17.1%. The reproducibility of iATT and MRI-PDFF was evaluated using the Bland-Altman analysis and intraclass correlation coefficients, whereas the diagnostic performance of each steatosis grade was examined using receiver operating characteristic analysis. RESULTS: The Bland-Altman analysis indicated excellent reproducibility with minimal fixed bias between iATT and MRI-PDFF. The area under the curve for distinguishing steatosis grades 1, 2, and 3 were 0.887, 0.882, and 0.867, respectively. A skin-to-capsula distance of ≥ 25 mm was identified as the only significant factor causing the discrepancy. No interaction between MRI-logPDFF and MRE-LSM on iATT values was observed. CONCLUSIONS: Compared to MRI-PDFF, iATT showed excellent diagnostic accuracy in grading steatosis. iATT could be used as a diagnostic tool instead of MRI in clinical practice and trials. Trial registration This study was registered in the UMIN Clinical Trials Registry (UMIN000047411).

Diagnostic performance of shear wave measurement in the detection of hepatic fibrosis: A multicenter prospective study.

AIM: This study aimed to establish the shear wave measurement (SWM) cut-off value for each fibrosis stage using magnetic resonance (MR) elastography values as a reference standard. METHODS: We prospectively analyzed 594 patients with chronic liver disease who underwent SWM and MR elastography. Correlation coefficients (were analyzed, and the diagnostic value was evaluated by the area under the receiver operating characteristic curve. Liver stiffness was categorized by MR elastography as F0 (<2.61 kPa), F1 (≥2.61 kPa, <2.97 kPa, any fibrosis), F2 (≥2.97 kPa, <3.62 kPa, significant fibrosis), F3 (≥3.62 kPa, <4.62 kPa, advanced fibrosis), or F4 (≥4.62 kPa, cirrhosis). RESULTS: The median SWM values increased significantly with increasing fibrosis stage (p < 0.001). The correlation coefficient between SWM and MR elastography values was 0.793 (95% confidence interval 0.761-0.821). The correlation coefficients between SWM and MR elastography values significantly decreased with increasing body mass index and skin-capsular distance; skin-capsular distance values were associated with significant differences in sensitivity, specificity, accuracy, or positive predictive value, whereas body mass index values were not. The best cut-off values for any fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis were 6.18, 7.09, 8.05, and 10.89 kPa, respectively. CONCLUSIONS: This multicenter study in a large number of patients established SWM cut-off values for different degrees of fibrosis in chronic liver diseases using MR elastography as a reference standard. It is expected that these cut-off values will be applied to liver diseases in the future.

Advanced fibrosis leads to overestimation of steatosis with quantitative ultrasound in individuals without hepatic steatosis.

PURPOSE: The effect of hepatic fibrosis stage on quantitative ultrasound based on the attenuation coefficient (AC) for liver lipid quantification is controversial. The objective of this study was to determine how the degree of fibrosis assessed by magnetic resonance (MR) elastography affects AC based on the ultrasound-guided attenuation parameter according to the grade of hepatic steatosis, using magnetic resonance imaging (MRI)-derived proton density fat fraction (MRIderived PDFF) as the reference standard. METHODS: Between February 2020 and April 2021, 982 patients with chronic liver disease who underwent AC and MRI-derived PDFF measurement as well as MR elastography were enrolled. Multiple regression was used to investigate whether AC was affected by the degree of liver stiffness. RESULTS: AC increased as liver stiffness progressed in 344 patients without hepatic steatosis (P=0.009). In multivariable analysis, AC was positively correlated with skin-capsule distance (P<0.001), MR elastography value (P=0.037), and MRI-derived PDFF (P<0.001) in patients without hepatic steatosis. In 52 of 982 patients (5%), the correlation between AC and MRIderived PDFF fell outside the 95% confidence interval for the regression line slope. Patients with MRI-derived PDFF lower than their AC (n=36) had higher fibrosis-4 scores, albumin-bilirubin scores, and MR elastography values than patients with MRI-derived PDFF greater than their AC (n=16; P=0.018, P=0.001, and P=0.011, respectively). CONCLUSION: AC is affected by liver fibrosis (MR elastography value ≥6.7 kPa) only in patients without hepatic steatosis (MRI-derived PDFF <5.2%). These values should be interpreted with caution in patients with advanced liver fibrosis.

A comparative study of hepatic steatosis using two different qualitative ultrasound techniques measured based on magnetic resonance imaging-derived proton density fat fraction.

AIM: This study aimed to evaluate the diagnostic performance of attenuation measurement (ATT; dual-frequency method) and improved algorithm of ATT (iATT; reference method) for the assessment of hepatic steatosis using magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) as the reference standard. METHODS: We prospectively analyzed 427 patients with chronic liver disease who underwent ATT, iATT, or MRI-derived PDFF. Correlation coefficients were analyzed, and diagnostic values were evaluated by area under the receiver operating characteristic curve (AUROC). The steatosis grade was categorized as S0 (<5.2%), S1 (≥5.2%, <11.3%), S2 (≥11.3%, <17.1%), and S3 (≥17.1%) according to MRI-derived PDFF values. RESULTS: The median ATT and iATT values were 0.61 dB/cm/MHz (interquartile range 0.55-0.67 dB/cm/MHz) and 0.66 dB/cm/MHz (interquartile range 0.57-0.77 dB/cm/MHz). ATT and iATT values increased significantly as the steatosis grade increased in the order S0, S1, S2, and S3 (p < 0.001). The correlation coefficients between ATT or iATT values and MRI-derived PDFF values were 0.533 (95% confidence interval [CI] 0.477-0.610) and 0.803 (95% CI 0.766-0.834), with a significant difference between them (p < 0.001). For the detection of hepatic steatosis of ≥S1, ≥S2, and ≥S3, iATT yielded AUROCs of 0.926 (95% CI 0.901-0.951), 0.913 (95% CI 0.885-0.941), and 0.902 (95% CI 0.869-0.935), with significantly higher AUROC values than for ATT (p < 0.001, p < 0.001, p = 0.001). CONCLUSION: iATT showed excellent diagnostic performance for hepatic steatosis, and was strongly correlated with MRI-derived PDFF, with AUROCs of ≥0.900.

Intra-individual comparison of liver stiffness measurements by magnetic resonance elastography and two-dimensional shear-wave elastography in 888 patients.

PURPOSE: Quantitative elastography methods, such as ultrasound two-dimensional shear-wave elastography (2D-SWE) and magnetic resonance elastography (MRE), are used to diagnose liver fibrosis. The present study compared liver stiffness determined by 2D-SWE and MRE within individuals and analyzed the degree of agreement between the two techniques. METHODS: In total, 888 patients who underwent 2D-SWE and MRE were analyzed. Bland-Altman analysis was performed after both types of measurements were log-transformed to a normal distribution and converted to a common set of units using linear regression analysis for differing scales. The expected limit of agreement (LoA) was defined as the square root of the sum of the squares of 2D-SWE and MRE precision. The percentage difference was expressed as (2D-SWEMRE)/ mean of the two methods×100. RESULTS: A Bland-Altman plot showed that the bias and upper and lower LoAs (ULoA and LLoA) were 0.0002 (95% confidence interval [CI], -0.0057 to 0.0061), 0.1747 (95% CI, 0.1646 to 0.1847), and -0.1743 (95% CI, -0.1843 to -0.1642), respectively. In terms of percentage difference, the mean, ULoA, and LLoA were -0.5944%, 19.8950%, and -21.0838%, respectively. The calculated expected LoA was 17.1178% (95% CI, 16.6353% to 17.6002%), and 789 of 888 patients (88.9%) had a percentage difference within the expected LoA. The intraclass correlation coefficient of the two methods indicated an almost perfect correlation (0.8231; 95% CI, 0.8006 to 0.8432; P<0.001). CONCLUSION: Bland-Altman analysis demonstrated that 2D-SWE and MRE were interchangeable within a clinically acceptable range.

Combined ultrasound and magnetic resonance elastography predict hepatocellular carcinoma after hepatitis C virus eradication.

AIM: Elastography is an established, noninvasive method for measuring liver stiffness using to 2-D shear-wave elastography (2D-SWE) or magnetic resonance elastography (MRE). The aim of this study was to determine the usefulness of combined measurement using 2D-SWE and MRE to stratify the risk of developing hepatocellular carcinoma (HCC) in patients who achieved hepatitis C virus eradication. METHODS: Five hundred and twenty-five patients who underwent 2D-SWE and MRE before antiviral therapy and who achieved eradication were enrolled. The optimal 2D-SWE and MRE cutoff values were determined using time-dependent receiver operating characteristic (ROC) curves for predicting HCC development. Inverse probability of treatment weighting (IPTW) and a Cox proportional hazards model were used to adjust the cumulative incidence rate of HCC development for potential imbalances. RESULTS: Time-dependent ROC analysis showed that the optimal cut-off values of 2D-SWE and MRE for predicting HCC development were 11.7 and 4.5 kPa, respectively. The IPTW-adjusted cumulative incidence rate of HCC development in patients with both an 2D-SWE value ≥ 11.7 kPa and an MRE value ≥ 4.5 kPa had a higher hazard ratio (28.080; 95% confidence interval, 5.527-132.600; p < 0.001) than those with either an 2D-SWE value < 11.7 kPa or an MRE value < 4.5 kPa. CONCLUSIONS: The combined measurement of 2D-SWE and MRE was very effective for identifying patients at high risk of HCC development. US-based elastography should be performed first, and if the 2D-SWE value is high, MRE should then be carried out to confirm the degree of liver stiffness.

Liver Stiffness Measurements by 2D Shear-Wave Elastography: Effect of Steatosis on Fibrosis Evaluation.

BACKGROUND. Hepatic steatosis has been found not to affect liver stiffness measurements (LSM) from MR elastography (MRE). However, the effect of steatosis on LSM from 2D shear-wave elastography (SWE) remains controversial. OBJECTIVE. The purpose of this study was to evaluate the effect of hepatic steatosis on the diagnostic performance of LSM from 2D SWE (LSM2D SWE) for evaluation of liver fibrosis with LSM from MRE (LSMMRE) as the reference standard. METHODS. This retrospective study included 888 patients (442 women, 446 men; median age, 67 years) with chronic liver disease who underwent LSM by both 2D SWE and MRE within a 3-month window. Steatosis was also assessed on ultrasound examinations by ultrasound-guided attenuation parameter (UGAP) and on MRI examinations by proton density fat fraction (PDFF). Fibrosis stages and steatosis grades were classified according to previously established thresholds. The effect of steatosis on LSM2D SWE was evaluated by Kruskal-Wallis tests with post hoc tests and ROC analysis. RESULTS. LSM2D SWE were significantly higher in patients with severe steatosis than those without steatosis by MRI PDFF among patients with F0 fibrosis (5.5 kPa [IQR, 4.7-6.0 kPa] vs 4.7 kPa [IQR, 4.2-5.5 kPa], p = .009) and F1 fibrosis (6.3 kPa [IQR, 6.0-7.2 kPa] vs 5.9 kPa [IQR, 5.0-6.6 kPa], p = .009). LSM2D SWE were significantly higher in patients with severe steatosis than those without steatosis by UGAP among patients with F1 fibrosis (6.6 kPa [IQR, 5.9-7.3 kPa] vs 5.9 kPa [IQR, 5.1-6.5 kPa], p = .008). Otherwise, LSM2D SWE did not vary significantly across steatosis grades at a given fibrosis stage (all p > .05). Sensitivity and specificity for ≥ F1 fibrosis were 63.8% and 91.5% in patients without versus 60.4% and 80.9% in patients with severe steatosis by MRI PDFF and were 62.4% and 91.5% in patients without versus 72.1% and 78.3% in patients with severe steatosis by UGAP. CONCLUSION. Severe hepatic steatosis may result in overestimation of LSM2D SWE in patients without or with mild steatosis, reducing the specificity of liver fibrosis detection. CLINICAL IMPACT. Assessment of UGAP at 2D SWE may help identify patients in whom LSM2D SWE should be assessed with caution. In patients with no or mild steatosis by 2D SWE and severe steatosis by UGAP, MRE helps provide a more reliable measure of liver fibrosis.

Intra-individual Comparisons of the Ultrasound-Guided Attenuation Parameter and the Magnetic Resonance Imaging-Based Proton Density Fat Fraction Using Bias and Precision Statistics.

Ultrasound-based techniques using the attenuation coefficient, including the ultrasound-guided attenuation parameter (UGAP), have been developed for the quantification of hepatic steatosis. The magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) is considered to be more accurate than liver biopsy for liver fat quantification. The aim of this study was to perform intra-individual comparisons of UGAP and MRI-PDFF for determining hepatic steatosis grade. The study enrolled 309 patients who underwent UGAP and MRI-PDFF measurements. Bland-Altman analysis was conducted after transforming MRI-PDFF values to a normal distribution and converted to a common set of units using linear regression analysis for differing scales. The expected limits of agreement (LOA) was defined as the square root of the sum of the squares of UGAP and MRI-PDFF precision. A Bland-Altman plot revealed that the bias and upper and lower LOAs (ULOA and LLOA) were -0.0047, 0.1160 and -0.1255, respectively. The percentage difference indicated that the mean, ULOA and LLOA were -1.1434%, 18.1723% and -20.4590%, respectively. The calculated expected LOA was 18.5449%, and 283 of 309 patients (91.6%) had a percentage difference within 18.5449%. Bland-Altman analysis revealed that UGAP and MRI-PDFF were interchangeable within a clinically acceptable range.

Prediction of Hepatocellular Carcinoma by Liver Stiffness Measurements Using Magnetic Resonance Elastography After Eradicating Hepatitis C Virus.

INTRODUCTION: Liver fibrosis stage is one of the most important factors in stratifying the risk of developing hepatocellular carcinoma (HCC). We evaluated the usefulness of liver stiffness measured by magnetic resonance elastography (MRE) to stratify the risk of developing HCC in patients who underwent MRE before receiving direct-acting antivirals (DAAs) and subsequently achieved sustained virological response (SVR). METHODS: A total of 537 consecutive patients with persistent hepatitis C virus who underwent initial MRE before DAA therapy and achieved SVR were enrolled. Factors associated with HCC development were analyzed by univariate and multivariate Cox proportional hazards models. RESULTS: Albumin-bilirubin score ≥ -2.60 (adjusted hazard ratio [aHR] 6.303), fibrosis-4 (FIB-4) score >3.25 (aHR 7.676), and MRE value ≥4.5 kPa (aHR 13.190) were associated with HCC development according to a univariate Cox proportional hazards model. A multivariate Cox proportional hazards model showed that an MRE value ≥4.5 kPa (aHR 7.301) was the only factor independently associated with HCC development. Even in patients with an FIB-4 score >3.25, the cumulative incidence rate of HCC development in those with an MRE value <4.5 kPa was significantly lower than that in patients with an MRE value ≥4.5 kPa. DISCUSSION: Liver stiffness measured by MRE before DAA therapy was an excellent marker for predicting subsequent HCC development in patients with hepatitis C virus infection who achieved SVR. The same results were observed in patients with high FIB-4 scores.

Attenuation imaging based on ultrasound technology for assessment of hepatic steatosis: A comparison with magnetic resonance imaging-determined proton density fat fraction.

AIM: A new method has recently been developed for diagnosing hepatic steatosis based on attenuation measurement using ultrasound. We investigated the ability of attenuation imaging (ATI) to detect steatosis that was identified by proton density fat fraction (PDFF) on magnetic resonance imaging (MRI) in patients with chronic liver disease. METHODS: A total of 119 patients with chronic liver disease (non-B, non-C) were analyzed. The relationship between ATI values and steatosis grades determined by PDFF was evaluated. Additionally, the diagnostic ability of ATI was evaluated using receiver operating characteristic curve analysis, and the correlation between ATI values and PDFF values was determined. RESULTS: The ATI values of steatosis grades 0, 1, 2, and 3 were 0.55, 0.61, 0.74, and 0.84 dB/cm/MHz, respectively (P < 0.001). There was a statistically significant trend of higher ATI values with higher steatosis grades (P < 0.001). The correlation coefficient (r) between PDFF values and ATI values was 0.70 (95% confidence interval [CI] 0.59-0.78; P < 0.001), corresponding to a strong relationship. The diagnostic ability of ATI for steatosis grades ≥1, ≥2, and 3, as determined by PDFF, were 0.81 (95% CI 0.73-0.89), 0.87 (95% CI 0.79-0.96), and 0.94 (95% CI 0.89-0.98), respectively. The r between PDFF values and ATI values was 0.49 (95% CI 0.31-0.63; P < 0.001) for patients with mild or no steatosis (grade ≤1), and 0.75 (95% CI 0.57-0.86; P < 0.001) for obese patients (body mass index ≥25 kg/m2 ). CONCLUSION: ATI values had an excellent diagnostic ability to detect hepatic steatosis.

Impact of the introduction of direct-acting anti-viral drugs on hepatocarcinogenesis: a prospective serial follow-up MRI study.

BACKGROUND: We conducted a prospective study using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) to determine whether sustained virological response (SVR) by direct-acting anti-viral (DAA) drugs suppresses hepatocarcinogenesis in patients with hepatitis C virus (HCV) infection. AIM: To use serial Gd-EOB-MRI to assess the impact of DAAs on hepatocarcinogenesis. METHODS: Between February 2008 and December 2018, 1083 consecutive patients with HCV infection underwent Gd-EOB-MRI. Of these, 719 patients were enrolled, including 210 patients in the 'Non-DAA group', who did not receive DAAs before the introduction of DAAs, and 509 patients in the 'DAA group', who achieved SVR after the introduction of DDAs. Factors associated with hepatocarcinogenesis were analysed by a Cox proportional hazard model. In addition, hepatocarcinogenesis was classified into two types, 'multistep' and 'de novo', on the basis of Gd-EOB-MRI findings. Factors associated with each type were analysed by Fine and Gray proportional hazards models. RESULTS: Hepatocarcinogenesis was observed in 67 of 719 (9.3%) patients. Factors associated with hepatocarcinogenesis were male gender, albumin-bilirubin (ALBI) grade 2 or 3, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) ≥5%, the presence of nonhypervascular hypointense nodules (NHHNs) and Non-DAA group. Of 67 patients, multistep hepatocarcinogenesis occurred in 58 patients (86.6%) and de novo hepatocarcinogenesis occurred in nine patients (13.4%). Factors associated with multistep hepatocarcinogenesis were male gender and Non-DAA group. CONCLUSION: The eradication of HCV by DAA therapy reduces multistep hepatocarcinogenesis.

Liver stiffness does not affect ultrasound-guided attenuation coefficient measurement in the evaluation of hepatic steatosis.

AIM: Recently, a new method has been developed to diagnose hepatic steatosis with attenuation coefficients based on the ultrasound-guided attenuation parameter (UGAP). We investigated whether fibrosis identified by hepatic stiffness measurements based on magnetic resonance elastography (MRE) affects attenuation coefficient measurement using UGAP for the evaluation of hepatic steatosis. METHODS: A total of 608 patients with chronic liver disease were analyzed. Correlations between magnetic resonance imaging-determined proton density fat fraction (PDFF) or MRE value and attenuation coefficients were evaluated. In addition, the interaction between hepatic fibrosis and the attenuation coefficient was analyzed. RESULTS: The correlation coefficient (r) between PDFF values and attenuation coefficient values was 0.724, indicating a strong relationship. Conversely, the r between MRE values and attenuation coefficient values was -0.187, indicating almost no relationship. In the multiple regression assessment of the effect of PDFF and MRE on the attenuation coefficient based on UGAP, the P-values for PDFF, MRE, and PDFF × MRE were < 0.001, 0.277, and 0.903, respectively. In patients with non-alcoholic fatty liver disease (n = 169), the r between PDFF values and attenuation coefficient values was 0.695, indicating a moderate relationship. Conversely, the r between MRE values and attenuation coefficient values was -0.068, indicating almost no relationship. In the multiple regression assessment of the effect of PDFF and MRE on the attenuation coefficient based on UGAP, the P-values for PDFF, MRE, and PDFF × MRE were <0.001, 0.948, and 0.706, respectively. CONCLUSION: UGAP-determined attenuation coefficient was weakly affected by liver stiffness, an indicator of hepatic fibrosis.

Diagnostic accuracy for macroscopic classification of nodular hepatocellular carcinoma: comparison of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and angiography-assisted computed tomography.

BACKGROUND: The macroscopic type of hepatocellular carcinoma (HCC) is a predictor of prognosis. We clarified the diagnostic value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in the macroscopic classification of nodular hepatocellular carcinoma (HCC) as compared to angiography-assisted computed tomography (CT). METHODS: A total of 71 surgically resected nodular HCCs with a maximum diameter of ≤5 cm were investigated. HCCs were evaluated preoperatively using Gd-EOB-DTPA-enhanced MRI and angiography-assisted CT. HCCs were pathologically classified as simple nodular (SN), SN with extranodular growth (SN-EG), or confluent multinodular (CMN). SN-EG and CMN were grouped as non-SN. Five readers independently reviewed the images using a five-point scale. We examined the accuracy of both imaging modalities in differentiating between SN and non-SN HCC. RESULTS: Overall, the area under the receiver operating characteristic curve (A z ) for the diagnosis of non-SN did not differ between Gd-EOB-DTPA-enhanced MRI and angiography-assisted CT [0.879 (95% confidence interval (CI), 0.779-0.937) and 0.845 (95% CI, 0.723-0.919), respectively]. For HCCs >2 cm, the A z for Gd-EOB-DTPA-enhanced MRI was greater than 0.9. The sensitivity, specificity, and accuracy of Gd-EOB-DTPA-enhanced MRI for identifying non-SN were equal to or higher than values with angiography-assisted CT in all three categories (all tumors, ≤2 cm, and >2 cm), but the differences were not statistically significant. CONCLUSIONS: Using Gd-EOB-DTPA-enhanced MRI to assess the macroscopic findings in nodular HCC was equal or superior to using angiography-assisted CT.

Evolution of hypointense hepatocellular nodules observed only in the hepatobiliary phase of gadoxetate disodium-enhanced MRI.

OBJECTIVE: We sought to determine whether hypointense hepatocellular nodules observed in the hepatobiliary phase of MRI enhanced with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (gadoxetate disodium) progress to hypervascular hepatocellular carcinoma. MATERIALS AND METHODS: Gadoxetate disodium-enhanced MRI was repeated for 30 patients with 49 nodules determined to be hypointense in the hepatobiliary phase but nonenhancing in the arterial phase of dynamic MRI. The correlation between characteristics of hypointense nodules with slightly or markedly low signal intensity relative to surrounding liver parenchyma and their progression to hypervascular hepatocellular carcinoma was analyzed in cirrhotic livers. All patients underwent angiography-assisted CT before MRI. The rate of progression to classic hepatocellular carcinoma was calculated by the Kaplan-Meier method. RESULTS: The overall 6- and 12-month cumulative incidences of vascularization were 27.6% and 43.5%. The 6- and 12-month cumulative incidences of vascularized nodules with a maximum diameter 15 mm or greater were 43.3% and 77.3% and a maximum diameter less than 15 mm were 16.9% and 16.9%. The difference between these incidences was significant (p = 0.0147). CONCLUSION: Hypointense nodules with a maximum diameter of at least 15 mm often become hypervascular. Therefore, patients with hypointense nodules characterized by a maximum diameter of 15 mm or greater should be observed carefully because of the high incidence of vascularization.

Evaluation of pathological features of hepatocellular carcinoma by contrast-enhanced ultrasonography: comparison with pathology on resected specimen.

Features of hepatocellular carcinoma (HCC) observed by contrast-enhanced ultrasonography (CEUS) were compared to pathological features of corresponding resected HCC specimens, to evaluate the ability of CEUS to depict the pathological features of HCC. We investigated 50 HCC nodules that were treated by surgical resection. All nodules had been examined by CEUS with intravenous contrast agent (Levovist) before surgery. CEUS findings were divided into three phases for evaluation and classification of enhancement patterns: two vascular phases (arterial phase and portal venous phase) and the delayed phase. Pathological examination focused on differentiation and on the presence or absence of a tumor capsule, intratumoral septum, and intratumoral necrosis. All 21 nodules that showed a linear or annular vessel around the tumor margin in the arterial phase had capsular formation. Of the 27 nodules that showed heterogeneous perfusion in the portal venous phase, 21 (77.8%) had an intratumoral septum and 23 (85.2%) showed intratumoral necrosis. All nodules that were depicted as a defect with an unclear margin in the delayed phase were well-differentiated HCCs, whereas all nodules that were depicted as a defect with a clear margin were moderately or poorly differentiated HCCs. From our observations, the arterial, portal venous, and delayed phases of CEUS could reflect different pathological aspects of HCC. Some pathological characteristics of HCC might be evaluated preoperatively and non-invasively, by means of combined analysis of three phases of CEUS findings.

Comparison of IV contrast-enhanced sonography and histopathology of pancreatic cancer.

OBJECTIVE: We compared contrast-enhanced sonography findings with pathologic findings in pancreatic cancer to evaluate the ability of contrast-enhanced sonography to depict the pathologic changes associated with pancreatic cancer. SUBJECTS AND METHODS: Thirty-four patients with pancreatic cancer who underwent surgery were investigated. Sonography was performed with contrast material (Levovist) for all patients before surgery. Pathologic findings were evaluated on the basis of the resected cancer specimens. We compared contrast-enhanced sonography findings with pathologic findings. RESULTS: All tumors that were hyperechoic on contrast-enhanced sonography were papillary adenocarcinoma, and all tumors that were hypoechoic on contrast-enhanced sonography were ductal adenocarcinoma. Among ductal adenocarcinomas, five (71.4%) of seven tumors for which the size of the hypoechoic area was unchanged on contrast-enhanced sonography had clear tumor margins with no infiltration or inflammation in the margin. In contrast, all tumors for which the size of the hypoechoic area was reduced on contrast-enhanced sonography had unclear tumor margins with infiltration of cancerous cells and inflammation. Nine (90%) of 10 tumors that showed partial contrast enhancement or a vascular shadow in a hypoechoic area had large or medium-sized vessels within a tumor at pathology. In contrast, only one (4.8%) of 21 tumors that did not show the vascular shadow in a hypoechoic area had no large or medium-sized vessels in a tumor. CONCLUSION: Contrast-enhanced sonography well reflects the pathologic changes of pancreatic cancer and will provide useful information in a pretreatment evaluation. Further studies with a large number of patients will be required to confirm this finding.

Assessment of tumor hemodynamics in small hepatocellular carcinoma: comparison of Doppler ultrasonography, angiography-assisted computed tomography, and pathological findings.

AIM: We evaluated the usefulness of Doppler ultrasonography (DUS) for the analysis of tumor hemodynamics in small hepatocellular carcinoma (HCC). METHODS: We compared Doppler ultrasound (DUS) findings with angiography-assisted computed tomography (Angio-CT) such as CT during arterial portography and during hepatic arteriography in the evaluation of the intratumoral hemodynamics, and with pathologic findings in 45 small HCC nodules (< or =3.0 cm in diameter) of 43 patients. DUS flow pattern of each nodule was categorized into three types: afferent continuous flow (Type 1), afferent pulsatile flow with afferent continuous flow (Type 2), and afferent pulsatile flow without afferent continuous flow (Type 3). Intratumoral blood supply was determined by Angio-CT, and pathologic findings were evaluated on resected or biopsied specimen. RESULTS: Based on Angio-CT findings, Type 1 nodules showed decreased arterial blood supply (ABS) without decreased portal blood supply (PBS). Type 2 nodules showed unchanged ABS but decreased PBS. Type 3 nodules showed both increased ABS and decreased PBS. DUS findings well represented blood supply of HCC evaluated by Angio-CT. In addition, all Type 1 and 2 nodules were well-differentiated HCC, and all Type 3 nodules were moderately or poorly differentiated HCC; DUS findings well reflected differentiation of HCC. CONCLUSIONS: DUS is a non-invasive imaging method and can be used for the evaluation of the stage of malignancy of small HCC.

Comparison of contrast-enhanced harmonic ultrasonography and power Doppler ultrasonography for depicting vascularity of hepatocellular carcinoma identified by angiography-assisted CT.

The sensitivity of contrast-enhanced harmonic gray scale imaging was compared with that of power Doppler sonography in depicting tumor vascularity and contrast enhancement of hepatocellular carcinoma (HCC) identified by angiography-assisted computed tomography (CT). One hundred thirty-nine classic HCC nodules (108 patients), each appearing as a high-attenuation mass on early-phase CT during hepatic arteriography and as a perfusion defect on CT during arterial portography, were evaluated. Vascular findings and contrast enhancement patterns were evaluated by contrast-enhanced harmonic gray scale imaging. Arterial pulsatile flow into each nodule was checked by power Doppler sonography. Sensitivity of each modality for depicting tumor vascularity was examined by angiography-assisted CT findings as the gold standard. The sensitivity of contrast-enhanced harmonic gray scale imaging (134/139, 96.4%) was significantly greater than that of power Doppler sonography (96/139, 69.1%) (P<0.05). Twenty-six of twenty-seven nodules (96.3%) in the lateral segment, in which motion artifact is likely, were enhanced by contrast-enhanced harmonic gray scale imaging. Contrast-enhanced harmonic gray scale imaging is more sensitive than power Doppler sonography and is a noninvasive method that can be used as effectively as angiography-assisted CT to evaluate tumor vessels and contrast enhancement of HCC.