WFUMB Review Paper. Incidental Findings in Otherwise Healthy Subjects, How to Manage: Liver.

An incidental focal liver lesion (IFLL) is defined as a hepatic lesion identified in a patient imaged for an unrelated reason. They are frequently encountered in daily practice, sometimes leading to unnecessary, invasive and potentially harmful follow-up investigations. The clinical presentation and the imaging aspects play an important role in deciding if, and what further evaluation, is needed. In low-risk patients (i.e., without a history of malignant or chronic liver disease or related symptoms), especially in those younger than 40 years old, more than 95% of IFLLs are likely benign. Shear Wave liver Elastography (SWE) of the surrounding liver parenchyma should be considered to exclude liver cirrhosis and for further risk stratification. If an IFLL in a low-risk patient has a typical appearance on B-mode ultrasound of a benign lesion (e.g., simple cyst, calcification, focal fatty change, typical hemangioma), no further imaging is needed. Contrast-Enhanced Ultrasound (CEUS) should be considered as the first-line contrast imaging modality to differentiate benign from malignant IFLLs, since it has a similar accuracy to contrast-enhanced (CE)-MRI. On CEUS, hypoenhancement of a lesion in the late vascular phase is characteristic for malignancy. CE-CT should be avoided for characterizing probable benign FLL and reserved for staging once a lesion is proven malignant. In high-risk patients (i.e., with chronic liver disease or an oncological history), each IFLL should initially be considered as potentially malignant, and every effort should be made to confirm or exclude malignancy. US-guided biopsy should be considered in those with unresectable malignant lesions, particularly if the diagnosis remains unclear, or when a specific tissue diagnosis is needed.

The Staging of Newly Diagnosed Hepatocellular Carcinoma in Romania. A National Multicentric Study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a significant public health issue, with an increasing incidence and prevalence and a high incidence-to-mortality ratio. The prognosis of HCC depends on two competing factors, tumor burden and underlying liver disease severity, encompassed in the Barcelona Clinic Liver Cancer (BCLC) classification. To assess HCC staging and the way staging affects eligibility for treatment at the time of the first diagnosis in Romania in the setting of opportunistic diagnosis, in the absence of a national HCC screening policy. METHODS: Data regarding HCC staging, underlying liver disease, and eligibility for treatment at the time of diagnosis was analyzed using a prospectively maintained multicentric database, which included patients from the five largest tertiary care hepatology units in the country between June 2016 and February 2020. RESULTS: A consecutive series of 477 patients was included. The distribution within BCLC classes was as follows: very early (0) 7.1%, early (A) 34.3%, intermediate (B) 19.4%, advanced (C) 14.2%, terminal (D) 24.7%. At the time of the diagnosis, 198 (41.5%) were eligible for a curative intent treatment, while 359 (75.2%) were eligible for a disease-modifying therapy. 228 patients (47.8%) had decompensated liver disease at the time of diagnosis, the most common decompensating event being ascites (78.1%). CONCLUSIONS: A large proportion of HCC cases are diagnosed at the time of a decompensating event, severely restricting the therapeutic potential. Proactive diagnostic strategies should be implemented to improve the rate of actionable diagnosis.

A Statistical Approach to the Diagnosis and Prediction of HCC Using CK19 and Glypican 3 Biomarkers.

Various statistical models predict the probability of developing hepatocellular carcinoma (HCC) in patients with cirrhosis, with GALAD being one of the most extensively studied scores. Biomarkers like alpha-fetoprotein (AFP), AFP-L3, and des-g-carboxyprothrombin (DCP) are widely used alone or in conjunction with ultrasound to screen for HCC. Our study aimed to compare the effectiveness of Cytokeratin 19 (CK19) and Glypican-3 (GPC3) as standalone biomarkers and in a statistical model to predict the likelihood of HCC. We conducted a monocentric prospective study involving 154 participants with previously diagnosed liver cirrhosis, divided into two groups: 95 patients with confirmed HCC based on clinical, biological, and imaging features and 59 patients without HCC. We measured the levels of AFP, AFP-L3, DCP, GPC3, and CK19 in both groups. We used univariate and multivariate statistical analyses to evaluate the ability of GPC3 and CK19 to predict the presence of HCC and incorporated them into a statistical model-the GALKA score-which was then compared to the GALAD score. AFP performed better than AFP-F3, DCP, GPC3, and CK19 in predicting the presence of HCC in our cohort. Additionally, GPC3 outperformed CK19. We used multivariate analysis to compute the GALKA score to predict the presence of HCC. Using these predictors, the following score was formulated: 0.005*AFP-L3 + 0.00069*AFP + 0.000066*GPC3 + 0.01*CK19 + 0.235*Serum Albumin-0.277. The optimal cutoff was >0.32 (AUROC = 0.98, sensitivity: 96.8%, specificity: 93%, positive predictive value-95.8%, negative predictive value-94.8%). The GALKA score had a similar predictive value to the GALAD score for the presence of HCC. In conclusion, AFP, AFP-L3, and DCP were the best biomarkers for predicting the likelihood of HCC. Our score performed well overall and was comparable to the GALAD score.

Association between Dietary Habits and Sarcopenia in Patients with Liver Cirrhosis.

Sarcopenia and sarcopenic obesity are frequent complications of cirrhosis, and the dietary patterns of patients with these diseases significantly impact the development of both conditions. This study aims to evaluate the adequacy of the dietary intake of patients with liver cirrhosis. A total of 201 patients with liver cirrhosis were included in this analysis. We evaluated the nutritional status of the patients as stated by EWGSOP2 criteria. Subjects were divided into three groups: non-sarcopenic, sarcopenic, and with sarcopenic obesity. We conducted a dietary assessment three times over nonconsecutive 24 h periods within a month. According to EWGSOP2 criteria, combining low handgrip strength with low skeletal muscle index, the prevalence of sarcopenia was 57.2%. Sarcopenic obesity was found in 25.3% of patients. In the sarcopenic group of patients, the energy intake was lower than the current recommendations. Regarding protein intake, the consumption was relatively low in both sarcopenia and sarcopenic obesity samples of patients (0.85 g/kg body weight and 0.77 g/kg BW, p < 0.0001). Patients had a median of 2-3 eating episodes daily, and they often missed late-evening snacks. In conclusion, diet quality in cirrhotic patients was relatively poor, and energy and protein intakes were lower than suggested.

Usefulness of Imaging and Biological Tools for the Characterization of Portal Vein Thrombosis in Hepatocellular Carcinoma.

This study aims to evaluate the performance of contrast-enhanced ultrasound (CEUS) and biological tests to characterize portal vein thrombosis (PVT). We retrospectively analyzed 101 patients with PVT, liver cirrhosis, and hepatocellular carcinoma (HCC). In all patients, demographic, biologic, imaging, and endoscopic data were collected. All patients underwent CEUS and a second line imaging technique (CE-CT/MRI) to characterize PVT. Of the 101 cirrhotic subjects, 77 (76.2%) had HCC. CEUS had 98.6% sensitivity (Se) and 89.3% specificity (Sp) for the characterization of PVT type. A significant correlation was found between alpha-fetoprotein (AFP) levels and the PVT characterization at CEUS (r = 0.28, p = 0.0098) and CT/MRI (r = 0.3, p = 0.0057). Using the AFP rule-out cutoff values for HCC (AFP < 20 ng/dL), 78% of the subjects were correctly classified as having benign PVT, while 100% of the subjects were correctly classified as tumor-in-vein (TIV) when the rule-in cutoff value was used (AFP ≥ 200 ng/dL). Using multiple regression analysis, we obtained a score for classifying PVT. The PVT score performed better than CEUS (AUC­0.99 vs. AUC­0.93, p = 0.025) or AFP serum levels (AUC­0.99 vs. AUC­0.96, p = 0.047) for characterizing PVT. In conclusion, CEUS is a sensitive method for the characterization of PVT. The PVT score had the highest performance for PVT characterization.

Dynamic Changes in Liver Stiffness in Patients with Chronic Hepatitis B Undergoing Antiviral Therapy.

This is a retrospective single-center study that included 87 subjects. All subjects had chronic hepatitis B or HBV cirrhosis and underwent nucleos(t)ide analogs (NUC) treatment for more than one year. The study aimed to evaluate the dynamic changes in liver stiffness (LS) measured by transient elastography (TE) during a median interval of 64 months. Patients were assessed prior to starting therapy and followed up annually. Liver stiffness measurements (LSM) were performed annually, and ten valid LSMs were obtained in each session. Reliable LSMs were defined as the median value of 10 measurements with Interquartile range/median (IQR/M) ≤ 30%. A significant decrease in liver stiffness values (p < 0.001) was observed during follow-up. In patients with liver cirrhosis, the LSMs decreased significantly after only one year, 24.6 ± 4.3 kPa vs. 13.5 ± 4.2 kPa (p = 0.007), whereas the decrease in non-cirrhotic patients was not significant, 7.31 ± 3.62 vs. 6.80 ± 2.41 (p = 0.27). Liver stiffness decrease was more significant in patients with initially higher transaminases. Undetectable viral load was achieved in 73.5% of patients in year one, 82.7% in year two, and 90.8% in year three of treatment. In conclusion, our study reveals a decrease in liver stiffness by TE in patients with chronic hepatitis B when undergoing anti-HBV therapy in the first two years. It can be used as a method for follow-up in patients undergoing NUC therapy.

Comparison of Different Nutritional Assessment Tools in Detecting Malnutrition and Sarcopenia among Cirrhotic Patients.

Malnutrition and sarcopenia are common complications of liver cirrhosis. This study compares the performance of different nutritional assessment techniques in detecting malnourished patients. Data from 156 patients with liver cirrhosis were collected. We assessed the nutritional status of these patients according to: Subjective Global Assessment (SGA); Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT), skinfold thickness (TSF), mid-upper arm circumference (MUAC), mid-upper arm muscle circumference (MUMC), handgrip strength (HGS), body mass index (BMI), and skeletal muscle index (SMI) evaluated by Contrast-Enhanced Computed Tomography (CT). According to EWGSOP2 criteria, combining low HGS with low SMI, the prevalence of malnutrition/sarcopenia was 60.2%. RFH-NPT, MUAC, MAMC, and HGS were excellent tests for detecting malnourished patients. Combining RFH-NPT with MUAC or MUMC increased diagnosis accuracy, AUC = 0.89, p < 0.0001. Age, Child-Pugh class C, albumin level, vitamin D deficiency, male gender, and alcoholic etiology were significantly associated with malnutrition. In conclusion, the prevalence of malnutrition among patients with cirrhosis was relatively high. Our study highlights the potential use of a simpler and inexpensive alternative that can be used as a valuable tool in daily practice, the combination between RFH-NPT and MUAC.

The Non-Invasive Ultrasound-Based Assessment of Liver Viscosity in a Healthy Cohort.

Liver fibrosis is the most significant prognostic factor in chronic liver disease (CLD). Clinical practice guidelines recommend the use of non-invasive techniques, such as two-dimensional shear-wave elastography (2D-SWE), to assess liver stiffness as a marker of fibrosis. Several other factors influence liver stiffness in addition to liver fibrosis. It is presumed that changes due to necro-inflammation modify the propagation of shear waves (dispersion). Therefore, new imaging techniques that investigate the dispersion properties of shear waves have been developed, which can serve as an indirect method of measuring liver viscosity (Vi PLUS). Defining the reference values in healthy subjects among different age groups and genders and analyzing the factors that influence these values is essential. However, published data on liver viscosity are still limited. This is the first study that aimed to assess the normal range of liver viscosity values in subjects with healthy livers and analyze the factors that influence them. One hundred and thirty-one consecutive subjects with healthy livers were enrolled in this prospective study. The results showed that Vi PLUS is a highly feasible method. Liver stiffness, age and BMI influenced the liver viscosity values. The mean liver viscosity by Vi PLUS in subjects with healthy livers was 1.59 Pa·s.

Assessment of Renal Allograft Stiffness and Viscosity Using 2D SWE PLUS and Vi PLUS Measures-A Pilot Study.

Elastography is a useful noninvasive tool for the assessment of renal transplant recipients. 2D-shear wave elastography (SWE) PLUS and viscosity plane-wave ultrasound (Vi PLUS) have emerged as novel techniques that promise to offer improved renal stiffness and viscosity measures due to improved processing algorithms. Methods: We performed a cross-sectional study of 50 kidney transplanted patients (16 women, 34 men; mean age of 47.5 ± 12.5; mean estimated glomerular filtration rate (eGFR) estimated by Chronic Kidney Disease Epidemiology Collaboration formula: 52.19 ± 22.6 mL/min/1.73 m2; and a mean duration after transplant of 10.09 ± 5 years). For every patient, we obtained five valid measurements of renal stiffness (obtained from five different frames in the cortex of the renal graft), and also tissue viscosity, with a C6-1X convex transducer using the Ultra-Fast™ software available on the Aixplorer Mach 30 ultrasound system (Supersonic Imagine, Aix-en-Provence, France). The median values of elastographic and viscosity measures have been correlated with the patients' demographic, biological, and clinical parameters. Results: We obtained a cut-off value of renal cortical stiffness of <27.3 kiloPascal(kPa) for detection of eGFR < 60 mL/min/1.73 m2 with 80% sensitivity and 85% specificity (AUC = 0.811, p < 0.0001), a cut-off value of <26.9 kPa for detection of eGFR < 45 mL/min/1.73 m2 with 82.6% sensitivity and 74% specificity (AUC = 0.789, p < 0.0001), and a cut-off value of <23 kPa for detection of eGFR < 30 mL/min/1.73 m2 with 88.8% sensitivity and 75.6% specificity (AUC = 0.852, p < 0.0001). We found a positive correlation coefficient between eGFR and the median measure of renal cortical stiffness (r = 0.5699, p < 0.0001), between eGFR the median measure of viscosity (r = 0.3335, p = 0.0180), between median depth of measures and renal cortical stiffness (r = −0.2795, p = 0.0493), and between median depth of measures and body mass index (BMI) (r = 0.6574, p < 0.0001). Our study showed good intra-operator agreement for both 2D SWE PLUS measures­with an intraclass correlation coefficient (ICC) of 0.9548 and a 95% CI of 0.9315 to 0.9719­and Vi PLUS, with an ICC of 0.8323 and a 95% CI of 0.7457 to 0.8959. The multivariate regression model showed that 2D SWE PLUS values were associated with eGFR, Vi PLUS, and depth of measures. Conclusions: Assessment of renal allograft stiffness and viscosity may prove to be an effective method for identifying patients with chronic allograft injury and could prove to be a low-cost approach to provide additional diagnostic information of kidney transplanted patients.

Contrast-Enhanced Ultrasonography with Arrival Time Parametric Imaging as a Non-Invasive Diagnostic Tool for Liver Cirrhosis.

Liver biopsy is the gold standard method for staging liver fibrosis, but it is an invasive procedure that is associated with some complications. There are also non-invasive techniques for assessing liver fibrosis, such as elastography and biological tests, but these techniques can fail in detection or generate false measurements depending on the subject's condition. This study aimed to determine whether liver fibrosis can be evaluated using contrast-enhanced ultrasonography with arrival time parametric imaging using the ultrasound machine's parametric image software, the method being called (CEUS-PAT). CEUS-PAT was performed on each subject using SonoVue as a contrast agent, and images showing liver parenchyma and the right kidney on a single screen were used for analysis in parametric imaging, which was performed using the proprietary software of the ultrasound system. The ratio between the kidney and liver arrival times was calculated. The study included 64 predominantly male (56.3%) subjects, 37 cirrhotic patients, and 27 healthy volunteers, with a mean age of 58.98 ± 8.90 years. Significant differences were found between the liver cirrhosis and healthy groups regarding CEUS-PAT, 0.83 ± 0.09 vs. 0.49 ± 0.11, p < 0.0001. The correlation between CEUS-PAT and VCTE was r = 0.81. The optimal cut-off value for detecting liver cirrhosis was >0.7, with an AUC of 0.98, p < 0.001, Se = 89.19%, Sp = 100%, PPV = 100%, and NPV = 87.1%. We demonstrate that CEUS-PAT achieves excellent performance in diagnosing liver cirrhosis and is a fast method for diagnosing liver cirrhosis that can even be applied in situations where the use of other methods is excluded.

Diagnosis of malignant biliary obstruction: pondering over the ERCP, MRCP and histology.

OBJECTIVE: To compare the diagnostic accuracy of endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance pancreatography (MRCP) and histological examination for malignant biliary obstruction. METHODS: This retrospective study included patients admitted for biliary obstruction caused by biliary tree malignancy that underwent ERCP, MRCP and histological examination. Data were collected from the medical records. The primary endpoints were the area under the receiver operating characteristic (AUROC) curve value, sensitivity, specificity and overall diagnostic accuracy of the three procedures in terms of a final diagnosis of obstructive biliary malignancy; and the agreement between ERCP, MRCP and histological examination with the final diagnosis. RESULTS: A total of 160 patients were included in the study (85 males, 53.1%; mean ± SD age, 69.31 ± 10.96 years). Considering the final diagnosis, the performance of MRCP, ERCP and histology in assessing biliary tumours produced AUROC values of 0.88 (95% confidence interval [CI] 0.75, 0.90), 0.94 (95% CI 0.85, 0.99) and 0.80 (95% CI 0.70, 0.82), respectively. ERCP presented higher sensitivity, overall diagnostic accuracy and agreement with the final diagnosis than MRCP and histological examination. CONCLUSION: These current data suggest that invasive methods such as ERCP with biopsy remain more reliable than non-invasive methods.

Comparative study between two 2D-Shear Waves Elastography techniques for the non-invasive assessment of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection.

AIMS: We aimed to compare the diagnostic performance of two 2D-Shear Wave Elastography (2D-SWE) techniques for the non-invasive assessment of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection using Transient Elas-tography (TE) as reference. MATERIAL AND METHODS: We enrolled 208 consecutive patients with chronic HCV infection, in which liver stiffness (LS) was evaluated in the same session using two 2D-SWE techniques: 2D-SWE.GE and 2D-SWE.SSI using TE as the method of reference. LS measurements were considered failures when no value was obtained after 10 attempts. RESULTS: Valid LSMs were obtained in 95.6% (199/208) of cases by 2D-SWE.GE, 92.7% (193/208) of cases by 2D-SWE.SSI, and in 94.7% (197/208) of cases by TE (p>0.05). The mean LS values by 2D-SWE.GE were significantly lower than those obtained by 2D-SWE.SSI: 10.3±3.8 kPa vs. 15±10.4 kPa (p<0.0001). 2D-SWE.GE LSMs correlated better with TE than 2D-SWE.SSI (r=0.75, p<0.0001 vs. r=0.57, p<0.0001, z test p=0.0012). Linear regression analysis showed a moderate correlation between LSMs obtained by 2D-SWE.GE and 2D-SWE.SSI (r=0.63, R2=0.4, P<0.0001). Pairwise comparison of receiver operating characteristics curves (ROC) found no significant differences between 2D-SWE.GE and 2D-SWE.SSI in identifying F≥2 fibrosis (0.97 vs. 0.96, P = 0.5650), F≥3 (0.97 vs. 0.95, P = 0.2935), or F=4 (0.97 vs. 0.96, p = 0.6914). CONCLUSIONS: Both 2D-SWE techniques had good feasibility for the noninvasive assessment of liver fibrosis. LS values obtained by 2D-SWE.GE were significantly lower than those obtained by 2D-SWE.SSI. No significant differences were found between both methods in staging liver fibrosis in patients with chronic HCV.

Assessing Baveno VI Criteria Using Liver Stiffness Measured with a 2D-Shear Wave Elastography Technique.

The present study evaluates the performance of Baveno VI criteria, using liver stiffness (LS) assessed with a 2D-SWE elastography technique, for predicting high-risk varices (HRV) in patients with compensated advanced chronic liver disease (cACLD). A secondary aim was to determine whether the use of spleen stiffness measurements (SSMs), as additional criteria, increases the performance of the 2D-SWE Baveno VI criteria. Data were collected from 208 subjects with cACLD, who underwent abdominal ultrasound, liver and spleen stiffness measurements, and upper digestive endoscopy. HRV were defined as grade 1 esophageal varices (EV) with red wale marks, grade 2/3 EV, and gastric varices. A total of 35.6% (74/208) of the included subjects had HRV. The optimal LS cut-off value for predicting HRV was 12 kPa (AUROC-0.80). Using both LS cut-off value < 12 kPa and a platelet cut-off value > 150 × 109 cells/L as criteria to exclude HRV, 52/208 (25%) subjects were selected, 88.5% (46/52) were without EV, 9.6% (5/52) had grade 1 EV, and 1.9% (1/52) had HRV. Thus 98% of the subjects were correctly classified as having or not having HRV and 25% of the surveillance endoscopies could have been avoided. Using SS < 13.2 kPa and a platelet cut-off value > 150 × 109 cells/L as additional criteria for the patients that were outside the initial ones, 32.7% of the surveillance endoscopies could have been avoided.

Contrast-enhanced ultrasound algorithm (ACR CEUS LI-RADSv 2017)- a valuable tool for the noninvasive diagnosis of hepatocellular carcinoma in patients with chronic liver disease.

AIMS: to evaluate the accuracy of LR-5 category from the latest Contrast-Enhanced Ultrasound algorithm (ACR CEUS LI-RADSv 2017) for the noninvasive diagnosis of hepatocellular carcinoma (HCC), in a real-life cohort of high-risk patients. MATERIAL AND METHODS: We retrospectively re-analysed the CEUS studies of 464 focal liver lesions (FLL) in 382 patients at high-risk for HCC (liver cirrhosis of any aetiology, chronic B or C hepatitis with severe fibrosis) using the ACR CEUS LI-RADSv 2017 algorithm. CEUS LI-RADS categories used for the diagnosis of HCC were: CEUS LR-5 (definitely HCC) and CEUS LR-TIV (HCC with macrovascular invasion). Contrast-enhanced CT, contrast-enhanced MRI, or histology were used as diagnostic reference methods to evaluate the CEUS LI-RADS classification of the 464 lesions. RESULTS: According to the reference method, the 464 lesions were classified as follows: 359 HCCs, 68 non-HCC-non-malignant lesions and 37 non-HCC malignant lesions. The diagnostic accuracy of LR-5 category for the diagnosis of hepatocellular carcinoma was 76.9%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.9%, 94.3 %, 97.7% and 49.5%, respectively. CONCLUSIONS: LR-5 category from ACR CEUS LI-RADSv 2017 algorithm, has good sensitivity, excellent specificity, and PPV for the diagnosis of HCC. The HCC rate increases from LR-3 to LR-5.

Ultrasound-Based Quantification of Fibrosis and Steatosis with a New Software Considering Transient Elastography as Reference in Patients with Chronic Liver Diseases.

The goal of this study was to evaluate the performance of two new ultrasound-based techniques (ShearWave PLUS elastography [2-D-SWE PLUS], SSp PLUS Imaging [SSp PLUS]) implemented on the Aixplorer Mach 30 ultrasound system (Supersonic Imagine, Aix-en-Provence, France) for the non-invasive assessment of liver steatosis and fibrosis, using transient elastography (TE) with the controlled attenuation parameter (CAP) as reference. This monocentric cross-sectional study included 133 consecutive adult patients with chronic hepatopathies. Liver stiffness and steatosis were evaluated in the same session using the techniques mentioned above. An excellent correlation was observed between liver stiffness measurements obtained with 2-D-SWE PLUS and TE (r = 0.92, p < 0.0001). The best cutoff value of 2-D-SWE PLUS for predicting F≥2 was 6.8 kPa; for F≥3, 8.4 kPa; and for F4, 11 kPa. With respect to steatosis evaluation, a strong negative correlation between CAP and SSp PLUS values (r = -0.70, p < 0.0001) was obtained. The best SSp PLUS cutoff value for predicting steatosis was 1537 m/s.

Quantification of Liver Fibrosis, Steatosis, and Viscosity Using Multiparametric Ultrasound in Patients with Non-Alcoholic Liver Disease: A "Real-Life" Cohort Study.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. This study aimed to evaluate the performance of four ultrasound-based techniques for the non-invasive multiparametric (MPUS) assessment of liver fibrosis (LF), steatosis (HS), and inflammation in patients with NAFLD. We included 215 consecutive adult patients with NAFLD (mean age: 54.9 ± 11.7; 54.5% were male), in whom LF, HS, and viscosity were evaluated in the same session using four new ultrasound-based techniques embedded on the Aixplorer MACH 30 system: ShearWave Elastography (2D-SWE.PLUS), Sound Speed Plane-wave UltraSound (SSp.PLUS), Attenuation Plane-wave UltraSound (Att.PLUS), and Viscosity Plane-wave UltraSound (Vi.PLUS). Transient Elastography (TE) with Controlled Attenuation Parameter (CAP) (FibroScan) were considered as control. All elastographic measurements were performed according to guidelines. Valid liver stiffness measurements (LSM) were obtained in 98.6% of patients by TE, in 95.8% of patients by 2D-SWE.PLUS/Vi.PLUS, and in 98.1% of patients by Att.PLUS/SSp.PLUS, respectively. Therefore, 204 subjects were included in the final analysis. A strong correlation between LSMs by 2D-SWE.PLUS and TE (r = 0.89) was found. The best 2D-SWE.PLUS cut-off value for the presence of significant fibrosis (F ≥ 2) was 7 kPa. Regarding steatosis, SSp.PLUS correlated better than Att.PLUS with CAP values: (r = -0.74) vs. (r = 0.45). The best SSp.PLUS cut-off value for predicting the presence of significant steatosis was 1524 m/s. The multivariate regression analysis showed that Vi.PLUS values were associated with BMI and LSM by 2D-SWE.PLUS. In conclusion, MPUS was useful for assessing fibrosis, steatosis, and inflammation in a single examination in patients with NAFLD.

Is There a Place for Elastography in the Diagnosis of Hepatocellular Carcinoma?

BACKGROUND AND AIMS: Elastography can provide information regarding tissue stiffness (TS). This study aimed to analyze the elastographic features of hepatocellular carcinoma (HCC) and the factors that influence intratumoral elastographic variability in patients with liver cirrhosis. METHODS: This prospective study included 115 patients with liver cirrhosis and hepatocellular carcinoma evaluated between June 2016-November 2019. A total of 88 HCC nodules visualized in conventional abdominal ultrasound (US) met the inclusion criteria and underwent elastographic evaluation. Elastographic measurements (EM) were performed in HCC and liver parenchyma using VTQ (Virtual Touch Quantification), a point shear wave elastography (pSWE) technique. In all patients, we performed contrast-enhanced ultrasound (CEUS), and the final diagnosis of HCC was established by contrast-enhanced-CT or contrast-enhanced-MRI. RESULTS: The mean VTQ values in HCCs were 2.16 ± 0.75 m/s. TS was significantly lower in HCCs than in the surrounding liver parenchyma 2.16 ± 0.75 m/s vs. 2.78 ± 0.92 (p < 0.001). We did not find significant differences between the first five and the last five EM, and the intra-observer reproducibility was excellent ICC: 0.902 (95% CI: 0.87-0.950). However, the tumor size, heterogeneity, and depth correlated with higher intralesional stiffness variability (p < 0.001). CONCLUSIONS: VTQ brings additional information for HCC characterization. Intra-observer reproducibility for both HCC and liver parenchyma was excellent. Knowing the stiffness of HCC's might endorse an algorithm-based approach towards focal liver lesions (FLLs) in liver cirrhosis.

Day-4 Lille Score Is a Good Prognostic Factor and Early Predictor in Assessing Therapy Response in Patients with Liver Cirrhosis and Severe Alcoholic Hepatitis.

Lille score at Day 7 (LM7) helps to predict the outcome of patients with severe alcoholic hepatitis (sAH) undergoing corticotherapy. Several scores such as Maddrey's discriminant function (MDF), MELD, ABIC, and GAHS are used for a 28-day mortality prognosis. Our study aimed to evaluate if the assessment of the Lille score at 4 days (LM4) is as useful as the Lille score at Day 7 (LM7) to predict response to corticosteroids and 28-day mortality and evaluate the utility of severity scores at admission for predicting the prognosis of patients with liver cirrhosis (LC) and severe alcoholic hepatitis (sAH). A retrospective study was performed, and all consecutive patients with AH and MDF > 32 without contraindications to corticosteroids were included. Prognostic scores were evaluated at admission, and 28-day mortality was assessed. Response to corticotherapy was assessed by LM4 and LM7. Results: A total of 55/103 patients with sAH (51.5%) had MDF > 32 and received corticosteroids. There was no difference between the proportion of patients with a responder LM4 versus LM7 (27% vs. 36%, p = 0.31). The mean value for LM4 was 0.64 ± 0.3 versus 0.60 ± 0.3 for LM7 (p = 0.48). Precisely 90.3% of patients were correctly identified as responders or not by LM4 compared with LM7. The best model for predicting 28-day mortality was composed of MELD and LM4/LM7, with an accuracy of 0.90 for both combinations. Conclusion: LM4 could be used instead of LM7 for predicting response to corticosteroid therapy in patients with sAH and LC, as well as 28-day mortality. Using LM4, we could avoid prolonged use of this therapy and its complications.

Ultrasound-Guided Attenuation Parameter (UGAP) for the quantification of liver steatosis using the Controlled Attenuation Parameter (CAP) as the reference method.

AIM: Nonalcoholic Fatty Liver Disease (NAFLD) is increasing in frequency in daily practice and evaluation of liver steatosis, fibrosis and inflammation severity are essential for prognosis assessment. The aim was to evaluate the usefulnessof a new liver steatosis quantification system - Ultrasound-Guided Attenuation Parameter (UGAP) from General Electric Healthcare, using Controlled Attenuation Parameter (CAP) as the reference method. MATERIAL AND METHOD: 179 consecutive subjects, in whom liver steatosis was assessed in the same session using UGAP, implemented on LOGIQ E10 system (GE Healthcare), and CAP (FibroScan, EchoSens). To discriminate between steatosis stages by CAP, we used the cut-offs recommended by the manufacturer: S1 (mild) - 230 dB/m, S2 (moderate) - 275 dB/m, S3 (severe) - 300 dB/m. RESULTS: We classified our cohort by means of CAP into the following groups: S0 (no steatosis): 48/176 (27.2%), S1 (mild): 56/176 (31.6%), S2 (moderate): 14/176 (7.3%) and S3 (severe): 59/176 (33.9%). The mean UGAP values increased with the steatosis grade and for each group were the following: S0: 198.3±25.7 dB/m, S1: 216.86±26.3 dB/m, S2: 237.79±26.3 dB/m, and S3: 270.8±31.62 dB/m respectively (p<0.001). A very good positive correlation was found between UGAP and CAP values (r=0.73, p<0.0001). The best cut-off values for predicting different grades of liver steatosis using CAP as the reference were: S1 - 192.5 dB/m (AUC 0.83); S2 - 231 dB/m (AUC 0.90) and S3 - 248 dB/m (AUC 0.91). CONCLUSION: UGAP seems to be a good method for liver steatosis quantification and correlates strongly with CAP values.