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Background: Direct acting antivirals(DAAs) are effective in reducing inflammatory ant fibrotic markers in patients with chronic hepatitis C virus(HCV) infection and to prevent liver-related complications. Two-dimensional shear wave elastography(2D-SWE) is an effective technique for the assessment of liver fibrosis., Aim: To evaluate changes in liver stiffness(LS) in HCV cirrhotic patients undergoing DAA therapy and to identify non-invasive parameters that predict the occurrence of liver-related events., Methods: We enrolled 229 patients who received DAAs between January 2015 and October 2018. Ultrasound parameters and laboratory data were assessed before treatment and 24(T1) and 48(T2) weeks after end of treatment. Patients were followed up every 6 months to evaluate the development of HCC and other liver related complications. Multiple Cox regression analysis was used to determine parameters associated with the development of complications., Results: Model for End-stage Liver Disease(MELD) score(HR 1.16; CI 95% 1.01-1.33; p = 0.026) and a change in LS at T2(1-year Delta LS) < 20%(HR 2.98; CI 95% 1.01-8.1; p = 0.03) were independently associated with HCC risk. One-year Delta-LS <20% was independently associated with the development of ascites(HR 5.08; CI 95% 1.03 - 25.14; p = 0.04)., Conclusions: Dynamic changes of 2D-SWE-measured LS after DAA therapy may be a useful tool to identify patients who are at higher risk of liver related complications., Competing Interests: Conflict of interest All authors confirm that there are no known conflicts of interest associated with this publication and there has been no financial support for this work that could have influenced its outcome., (Copyright © 2023. Published by Elsevier Ltd.)

Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model., Methods: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses., Results: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD., Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed., Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate whether changes in bowel perfusion parameters measured by dynamic-CEUS (D-CEUS) can be used for monitoring response to therapy in active Crohn disease (CD)., Methods: Fifty-four CD patients were evaluated with d-CEUS before (T0) and after 2 (T1), 6 (T2) and 12 weeks (T3) of anti-TNFα therapy. Variations from baseline were calculated for: peak intensity, PI; area under the curve, AUC; slope of wash in, P w ; time to peak, TP; mean transit time, MTT (median percentage values) and were correlated with combined endoscopic/clinical response after 12 weeks and clinical relapse within 6 months., Results: 70% of patients achieved combined endoscopic/clinical response (responders). The reduction in PI, AUC, P w and MTT between T1 and T0 was higher in responders. Relapsers (21%) showed significantly lower reduction in delta PI and P w at T1 and T2. At T3 they showed a new increase in PI and lower reduction in delta P w. In relapsers, AUC showed a significantly lower decrease at T2 and T3, TP showed a significant reduction at T3 and MTT showed a progressive increase at the different time-points, reaching the statistical significance at T3., Conclusions: d-CEUS might become a reliable predictor of combined endoscopic/clinical response and clinical relapse in CD., Competing Interests: Declaration of Competing Interest No potential conflicts of interest. No financial support., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Ultrasound (US) is frequently the first line imaging technique used in patients with abdominal pain and clinical suspicion of chronic pancreatitis (CP), but its role in the diagnosis and follow-up of CP is still controversial., Aims: We aimed to develop a dedicated score for the US staging of CP and to evaluate the agreement of this score with standard imaging techniques., Methods: Ninety consecutive patients with a diagnosis of CP referred to the pancreatic outpatient clinic of A. Gemelli Hospital between June and September 2018 were recruited in the study. Patients underwent pancreatic US to evaluate different morphological parameters to develop an US based score system, called the Gemelli UltraSound Chronic Pancreatitis (USCP) score., Results: The Gemelli USCP score significantly increased according to the Cambridge score for both mean value (p<0.0001) and each parameter evaluated (p<0.0001). Moreover, we found a significant correlation between the score and laboratory parameters related to pancreatic exocrine insufficiency such as vitamin D, B9, and B12 deficiency and fecal elastase values (p<0.0001)., Conclusions: The development of a dedicated US score could be useful in the follow up of patients with CP as alternative non-invasive technique to standard radiological imaging., Competing Interests: Declaration of Competing Interest No potential conflicts of interest. No financial support., (Copyright © 2020. Published by Elsevier Ltd.)

Intestinal ultrasonography has emerged as a cheap, non-invasive and readily accessible modality for the assessment of a number of gastroenterological diseases. Over the last decade, particularly due to the widespread use of biological agents in Inflammatory Bowel Disease (IBD), guidelines regarding management and follow-up advise more regular disease assessment and surveillance in order to guide treatment adjustments, and provide more personalised care. Given the young age of the majority of patients with IBD the availability of an alternative modality to harmful radiation or the risks of endoscopy for this indication offers an appealing advantage. Intestinal ultrasonography has been shown to be as sensitive and specific for detecting IBD as both computed tomography and magnetic resonance enterography, and endoscopic evaluation. More recent developments in the technology of ultrasonography equipment and the use of intravenous contrast agents (contrast enhanced ultrasonography, known as CEUS), have significantly increased the ability to both detect disease location, determine the disease activity and also potentially the difference between fibrotic and inflammatory segments. This review focusses specifically on the value of CEUS for the diagnosis of both Crohn's disease and Ulcerative Colitis, in determining disease activity, extraintestinal complications, determination of fibrosis as well as its more recent use in assessing and predicting response to biological and immunosuppressive therapies., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Sorafenib has become the standard first-line treatment for patients with advanced HCC and acts by inducing alterations in tumor vascularity. We wanted to evaluate the feasibility of dynamic CEUS (D-CEUS) as a predictor of early tumor response to sorafenib and to correlate functional parameters with clinical efficacy end points., Methods: Twenty-eight HCC patients treated with sorafenib 400mg bid were prospectively enrolled. CEUS was performed at baseline (T0) and after 15 (T1) and 30 (T2) days of treatment. Tumor vasculature was assessed in a specific harmonic mode associated with a perfusion and quantification software (Q-Lab, Philips). Variations between T1/T2 and T0 were calculated for five D-CEUS functional parameters (peak intensity, PI; time to PI, TP; area under the curve, AUC; slope of wash in, Pw; mean transit time, MTT) and were compared for responders and non-responders. The correlation between D-CEUS parameters, overall survival (OS), and progression-free survival (PFS) was also assessed. A p value <0.05 was considered statistically significant., Results: The percentage variation at T1 significantly correlated with response in three D-CEUS parameters (AUC, PI and Pw; p=0.002, <0.001, and 0.003, respectively). A decrease of AUC (p=0.045) and an increased/unchanged value of TP (p=0.029) and MTT (p=0.010) were associated with longer survival. Three D-CEUS parameters (AUC, TP, Pw) were significantly associated with PFS., Conclusions: D-CEUS provides a reliable and early measure of efficacy for anti-angiogenic therapies and could be an excellent tool for selecting patients who will benefit from treatment., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Treatment of Helicobacter pylori infection is becoming a very relevant problem especially in industrialized Countries. Although different therapeutic regimens are currently available, treatment failure remains a growing problem in daily medical practice. Several factors could play a role in the eradication failure, but the most relevant are antibiotic resistance and patient's compliance. While Helicobacter pylori resistance to amoxicillin is rare, clarithromycin and metronidazole resistance varies significantly from close to zero up to 25%. However, metronidazole in vitro resistance exhibits a lower impact on eradication success because resistance in vitro does not reflect that in vivo. Specific guidelines have then been published, mostly based on antibiotic resistance among different geographic areas. Basically, first-line and second-line regimens have been well defined; concerning third-line treatment Maastricht III guidelines suggest to adopt a culture-based approach. Culture is, however, expensive, invasive and available only in few specialized centres. An alternative approach may be to use an empirical strategy, based on the avoidance of repeating similar eradicating schemes in the same patients during the course of different eradicating regimens. For this approach we propose the acronym DANCE (Different Antibiotic No Culture Eradicating) strategy. When correctly applied, this approach showed to reach successful eradication in up to 99.5% of Helicobacter pylori-positive patients., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Adrenal insufficiency (AI) is reported in critically ill patients with cirrhosis and is associated with increased mortality. It is unclear if AI is an underlying condition or triggered by critical events (e.g. sepsis). We investigated AI in cirrhosis without infection or hemodynamic instability., Methods: A total of 101 consecutive patients with cirrhosis were studied. AI was defined by a total serum cortisol (TC) <18 μg/dl at 20 or 30 min after injection of 1 μg of tetracosactrin. Transcortin, calculated free cortisol (cFC), and free cortisol index (FCI) were assessed in a subgroup of 41 patients, with FCI>12 representing normal adrenal function., Results: AI was present in 38 patients (38%). Child score (median, 10 vs 7, p<0.0001), MELD score (median, 17 vs 12, p<0.0001), ascites (68% vs 37%, p<0.01), basal TC (median,7.6 vs 14.9 μg/dl, p<0.001), albumin (28 ± 0.8 vs 33 ± 0.7 g/L, p<0.0001), INR (median, 1.6 vs 1.2, p<0.0001), total bilirubin (median, 51 vs 31 μmol/L, p<0.05), total cholesterol (median, 120 vs 142, p<0.05), and LDL (median, 76 vs 81, p<0.05) were significantly different between those with and without AI. ROC curves showed a basal TC ≤ 12.8 μg/dl to be a cut-off value closely associated with AI. The cFC was significantly related to TC for baseline values (R=0.94, p<0.0001), peak values (R=0.90, p<0.0001), and delta values (R=0.95, p<0.0001), in patients with and without AI. However, no patient had a FCI<12., Conclusions: AI defined by an abnormal response to 1 μg tetracosactrin is frequent in stable patients with cirrhosis, in the absence of infections or hemodynamic instability and is related to the severity of liver disease. However, evaluation of the true incidence of AI should comprise direct assays of free cortisol. Clinical consequences of AI need to be explored., (Copyright © 2010 European Association for the Study of the Liver. All rights reserved.)