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Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

We aimed to investigate the diagnostic performance of new 2-D shear-wave elastography (SWE) with propagation maps and attenuation imaging (ATI) for quantification of fibrosis and steatosis in non- alcoholic fatty liver disease (NAFLD). Consecutive patients with NAFLD and healthy volunteers underwent liver stiffness measurement and steatosis quantification by means of vibration- controlled transient elastography coupled with the controlled attenuation parameter as the reference and by 2-D shear-wave elastography (2-D-SWE) with propagation maps and ATI as the investigational methods. We included 232 participants (164 in the NAFLD group and 68 in the healthy control group): 51.7%/49.3% women/men ; mean age, 54.2 +/- 15.2 y ; mean body mass index, 29.4 +/- 6.5 kg/m(2). Significant correlations were found between 2-D- SWE and vibration-controlled transient elastography (r = 0.71, p < 0.0001) and between ATI and the controlled attenuation parameter (r = 0.72, p < 0.0001). NAFLD-specific 2-D-SWE liver stiffness measurement cutoffs were as follows-F >= 2: 7.9 kPa (area under the curve [AUC] = 0.91) ; F >= 3: 10 kPa (AUC = 0.92) ; and F = 4: 11.4 kPa (AUC = 0.95). For steatosis, the best cutoffs by ATI were as follows-S1 = 0.73 dB/cm/MHz (AUC = 0.86) ; S2 = 0.76 dB/cm/MHz (AUC = 0.86) ; and S3 = 0.80 dB/cm/MHz (AUC = 0.83). According to Baveno VI criteria, the optimal 2-D-SWE liver stiffness measurement for diagnosing liver cirrhosis is 15.5 kPa (AUC = 0.94), and for ruling out compensated advanced chronic liver disease it is 9.2 kPa (AUC = 0.92). To conclude, 2-D-SWE with propagation maps and ATI is reliable for quantification of liver fibrosis and steatosis in patients with NAFLD.

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, p0.0001). 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, p0.0001) was obtained. The best SSp PLUS cutoff value for predicting steatosis was 1537 m/s.

Purpose To evaluate the feasibility and usefulness of two novel elastographic methods, integrated in the same ultrasound machine (Samsung-Medison RS85), one pSWE and one 2D-SWE, for liver fibrosis (LF) assessment using Transient Elastography (TE) as the reference method. Material and methods Our study included 115 subjects, with or without chronic liver disease, in which LF was evaluated in the same session by means of Transient Elastograpy (Fibroscan, EchoSens) and by pSWE and 2D-SWE techniques integrated in the same ultrasound machine (Samsung-Medison RS85 Ultrasound Machine). Reliable liver stiffness (LS) measurements were defined as follows: for TE as the median values of 10 measurements with a success rate of more than 60% and an interquartile range/median ratio (IQR/M) 0.5 and an IQR/M Results Reliable measurements by TE were obtained in 98.2% (113/115), by pSWE in 93.9% (108/115) and by 2D-SWE in 92.1% (106/115) subjects, so the final analysis included 101 patients. We divided the cohort into 3 groups: fibrosis 5.9 kPa (AUROC=0.95, 95% CI (0.89; 0.98), p 8 kPa (AUROC=0.98, 95% CI (0.94; 0.99), p 6.1 kPa (AUROC=0.93, 95% CI (0.86; 0.97), p 7.6 kPa (AUROC=0.98, 95% CI (0.93; 0.99), p Conclusion The novel pSWE and 2D-SWE are feasible methods for assessing liver fibrosis, both techniques strongly correlating with TE results.

The aim of the study was to assess the severity of liver fibrosis and steatosis in a cohort of type 2 diabetic patients, using non-invasive Methods: Transient Elastography (TE) and Controlled Attenuation Parameter (CAP). Material and Method: The study included 704 type 2 diabetic patients prospectively randomized, evaluated in the same session by means of TE and CAP (FibroScan, EchoSens) to assess both liver fibrosis and steatosis. Reliable liver stiffness measurements (LSM) were defined as the median value of 10 LSM with an IQR/median 300 db/m. Results: Out of 704 diabetics screened we excluded those with associated viral hepatitis, those with an AUDIT-C score ≥ 8 and those with unreliable LSM. The final analysis included 485 subjects (54.3% women, mean age 60 ± 9.5; mean BMI = 31.6 ± 6.1 kg/m2) with reliable LSM. 32.1% of patients had obesity grade I, 17.9 % had obesity grade II and 8.9% had obesity grade III (IMC ≥ 40 kg/m2). Mild, moderate and severe steatosis by means of CAP was found in 15.6%, 15.6 % and 59.3% cases, respectively. The median CAP values of patients with mild, moderate and severe steatosis were 260 db/m, 287.5 db/m and 354 db/m. Clinically relevant fibrosis was detected by means of TE in 19.6% (95/485) of subjects. Conclusion: In our group, 59.3% of diabetic patients had severe steatosis by means of CAP. Regarding the liver fibrosis, we found that 19.6% of them had severe fibrosis (TE ≥ 10.1kPa), suggesting the need for further assessment.

Background Liver stiffness (LS) measurement by elastographic methods is a noninvasive technique for the evaluation of liver fibrosis, which could also be used for predicting the presence of esophageal varices (EV) in patients with liver cirrhosis. Aim The aim of this study was to evaluate two ultrasound based elastographic methods as non-invasive markers for predicting the presence of EV, in a cohort of alcoholic liver cirrhosis patients. Material and Method The study included 77 patients diagnosed with compensated alcoholic liver cirrhosis, who underwent both upper endoscopy and LS assessment by two elastographic methods -Transient Elastography (TE) (Fibroscan/EchoSens) and Point shear wave elastography - Virtual Touch Tissue Quantification (VTQ) (Siemens Acuson S2000). Reliable LS measurements were defined for both methods as the median values of 10 measurements with an interquartile range/median ratio (IQR/M) Results 56 patients out of 77 had valid measurements by both elastographic methods and were included in the final analysis, 40/56 patients with EV. The best cut-off values to rule out the presence of EV in our cohort of alcoholic liver cirrhosis patients, with a NPV of 100% were: ≤ 20.1 kPa for TE (AUROC – 0.9; sensitivity-100%; specificity- 28%; PPV- 56%; NPV- 100%, Lr- 0, LR+1.38) and ≤ 2.1 m/s for VTQ (AUROC – 0.85; sensitivity-100%; specificity- 18%; PPV- 52%; NPV- 100%, Lr- 0, LR+1.21). Conclusion Using for TE the cut-off value ≤ 20.1 kPa and VTQ ≤ 2.1 m/s we can rule out quite accurately the presence of EV in patients with alcoholic liver cirrhosis.

In daily practice, many hepatological conditions, such as chronic viral hepatitis, non-alcoholic and alcoholic fatty liver disease (NAFLD and ALD, respectively) need evaluation. This evaluation can be made invasively (by liver biopsy) or non-invasively (by biological tests or by elastographic methods). Elastographic methods can be divided into ultrasound based or magnetic resonance based (MR-Elastography). According to the latest guidelines, (EFSUMB 2017 and WFUMB 2018) ultrasound based elastographic methods can be sub-divided into: Strain Elastography and Shear Wave Elastography (SWE). In hepatological field, SWE is mainly used for liver fibrosis assessment. According to the type of tissue stimulation, SWE can be divided into Transient Elastography (TE) and ARFI technologies (point SWE and 2D-SWE). Transient Elastography (TE) is the oldest elastographic method used in hepatology. Many guidelines and meta-analyses presented its value and limitations (mainly the presence of ascites), including the confounding factors. This method has been proven valuable in HCV and HBV chronic hepatitis, in NAFLD, ALD, post-transplant and in other conditions. The accuracy is increasing with the severity of fibrosis. The New FibroScan system includes a software for spleen stiffness assessment and has a supplementary ultrasound probe for the inspection of the liver, before stiffness evaluation. Point SWE (pSWE) is a quite simple method, working in real time. After the ultrasound examination of the liver, a box of 10/5 mm is placed at more than 1 cm bellow the liver capsule and a button is pressed to measure liver stiffness. The values are expressed in m/s or kPa. The first pSWE system was VTQ (Virtual Touch Quantification) from Siemens, and many papers and meta-analysis proved its good value to predict fibrosis severity in HCV, HBV or NAFLD patients. Later, ElastPQ from Philips was developed and showed a good predictive value in chronic liver disease. Other pSWE techniques were developed by Hitachi, Samsung and other companies. 2D-SWE is a real time elastographic technique, in which liver stiffness is expressed as a colour coded elastogram and also in numeric values. Studies demonstrated that some ultrasound experience is needed for quality measurements. The Aixplorer system from Supersonic Imagine, (SSI) was the first system on the market to use 2D-SWE, and good results of this method were published in several studies and meta-analyses. Other 2D-SWE technologies were developed by GE and Canon, showing good values for clinical practice. Comparative studies were performed in patients with chronic viral hepatitis or NAFLD, evaluating TE, pSWE and 2D-SWE, with liver biopsy as the gold standard. These studies demonstrated that comparable accuracies of al these methods. Studies have been made evaluating TE, pSWE and 2D-SWE as predictors of portal hypertension, but the results are still under discussion regarding pSWE and 2D-SWE. TE has been accepted as a tool to stratify patients at risk for clinically significant portal hypertension. The most recent topic in the field on the non-invasive assessment of liver diseases is the quantification of liver fat. CAP (Controlled Attenuation Parameter) from EchoSens implemented into the FibroScan device, was the first used for liver steatosis quantification. The correlation with histology is quite good (AUROC 0.80-0.85) and CAP is implemented into both the M and XL probes. More recently, other companies such as Hitachi or Canon implemented this type of quantification (attenuation) in their systems (ATT and ATI, respectively), both with interesting results. The same companies included in their latest machines algorithms evaluating the viscosity as a marker of the inflammation in the liver. In this respect, we go now in the direction of a multi-parametric elastographic approach of liver diseases, which quantifies stiffness, steatosis and inflammation. Confounding factors must be known regarding ultrasound based liver elastography to avoid clinical mistakes. In addition, the cut-offs values, which are ultrasound machine specific should be known. Finally, published papers showed the good predictive value of TE, pSWE and 2D-SWE for predicting liver fibrosis severity in daily practice. In conclusion, the body of evidence for ultrasound based elastography is enough strong to recommend this methods for liver diseases assessment. Liver elastography replaced in many cases liver biopsy.