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The primary end point was the compliance rate with guidelines. The secondaries were mortality, hospital stay, and costs.This study included 1904 patients with acute pancreatitis (AP): group A, diagnosed before 2013, and group B, after 2013.The compliance rate was 0.6%. The compliance rates increased for fluid resuscitation (3.3% vs 13.7%, P0.001), for antibiotics use (21.9% vs 28.1%, P = 0.002), for oral feeding (55.0% vs 49.7%, P = 0.007), and for correct use of endoscopic retrograde cholangiopancreatography (ERCP) (83% vs 91.9%, P0.001). Compliance to severity assessment with computed tomography (odds ratio [OR], 0.4; P = 0.029), parenteral nutrition recommendations (OR, 0.3; P = 0.009), and early surgery (OR, 0.3; P = 0.010) reduced the mortality. Compliance to antibiotic therapy (OR, 0.6; P0.001), correct use of parenteral nutrition (OR, 0.3; P0.001), correct use of ERCP (OR, 0.5; P0.001), and early surgery (OR, 0.3; P = 0.010) reduced hospital stay. The compliance reduced the costs for parenteral nutrition (P0.001), correct use of ERCP (P = 0.011), and surgery (P = 0.010).The adherence to guidelines for AP was low. Compliance could reduce mortality, prolonged hospital stay, and costs.

Over the last few years, capsule endoscopy has been established as a fundamental device in the practicing gastroenterologist’s toolbox. Its utilization in diagnostic algorithms for suspected small bowel bleeding, Crohn’s disease, and small bowel tumors has been approved by several guidelines. The advent of double-balloon enteroscopy has significantly increased the therapeutic possibilities and release of multiple devices (single-balloon enteroscopy and spiral enteroscopy) aimed at improving the performance of small bowel enteroscopy. Recently, some important innovations have appeared in the small bowel endoscopy scene, providing further improvement to its evolution. Artificial intelligence in capsule endoscopy should increase diagnostic accuracy and reading efficiency, and the introduction of motorized spiral enteroscopy into clinical practice could also improve the therapeutic yield. This review focuses on the most recent studies on artificial-intelligence-assisted capsule endoscopy and motorized spiral enteroscopy.

The burden of post-operative complications of patients undergoing liver resection for hepatocellular carcinoma (HCC) is a cause of morbidity and mortality. Recently, sarcopenia has been reported to influence the outcome of patients with cirrhosis. We aimed to assess factors associated with sarcopenia and its prognostic role in liver surgery candidates. We included all patients with compensated advanced chronic liver disease (cACLD) undergoing liver resection for primary HCC consecutively referred to the University of Bologna from 2014 to 2019 with an available preoperative abdominal CT-scan performed within the previous three months. A total of 159 patients were included. The median age was 68 years, and 80.5% of the patients were male. Sarcopenia was present in 82 patients (51.6%). Age and body mass index (BMI) were associated with the presence of sarcopenia at multivariate analysis. Thirteen (8.2%) patients developed major complications and 14 (8.9%) presented PHLF grade B-C. The model for end-stage liver disease score was associated with the development of major complications, whereas cACLD presence, thrombocytopenia, portal hypertension (PH), Child-Pugh score and Albumin-Bilirubin score were found to be predictors of clinically significative PHLF. The rate of major complications was 11.8% in sarcopenic patients with cACLD compared with no complications (0%) in patients without sarcopenia and cACLD (p = 0.032). The rate of major complications was significantly higher in patients with (16.3%) vs. patients without (0%) sarcopenia (p = 0.012) in patients with PH. In conclusion, sarcopenia, which is associated with age and BMI, may improve the risk stratification of post-hepatectomy major complications in patients with cACLD and PH.

The role of sarcopenia in predicting decompensation other than hepatic encephalopathy is unclear. We aimed to evaluate the prognostic role of sarcopenia, assessed by computed tomography (CT), in the development of ascites and mortality in patients with advanced chronic liver disease (ACLD) outside the liver transplantation (LT) setting.We retrospectively evaluated ACLD patients with liver stiffness measurement (LSM)10 kPa and an available CT scan within 6 months. Sarcopenia was defined as skeletal muscle index (SMI)50 and39 cm209 patients were included in the final analysis and sarcopenia was present in 134 (64.1%). During a median follow-up of 37 (20-63) months, 52 patients developed ascites, 24 underwent LT, and 30 died. Sarcopenia was found a predictive factor of decompensation with ascites (SHR 2.083, 95%-CI: 1.091-3.978), independently from the features of clinically significant portal hypertension (LSM≥21 kPa or portosystemic shunts). Sarcopenia (SHR: 2.744, 95%-CI: 1.105-6.816) and LSM≥21 kPa (SHR: 3.973, 95%-CI: 1.548-10.197) were independent risk factors for increased mortality.Sarcopenia and portal hypertension are two major and independent risk factors for decompensation with ascites and mortality in cirrhotic patients outside the LT context.

Portal hypertension is the main driver of complications in patients with advanced chronic liver disease (ACLD) and is defined by values of hepatic venous pressure gradient measurement (HVPG) >5 mmHg. Values of HVPG >= 10 mmHg determine the presence of clinically significant portal hypertension (CSPH), the main predictor of the risk of variceal bleeding, hepatic decompensation, and mortality. However, its measurement is invasive and requires high expertise, so its routine use outside third level centers or clinical trials is limited. In the last decades, several non-invasive tests (NITS) have been developed and validated for the diagnosis of portal hypertension. Among these, liver (LSM) and spleen stiffness measurement (SSM) are the most promising tools available, as they have been proven accurate to predict CSPH, high-risk esophageal varices, decompensation, and mortality in patients with ACLD. In the last Baveno VI Consensus proceedings, LSM evaluation was recommended for the first time for diagnosis of CSPH (LSM >20-25 kPa) and the screening of patients with a low probability of having high-risk varices (LSM 150.000/mm(3)). In this review, we aimed to summarize the growing evidence supporting the use of non-invasive tests for the evaluation of portal hypertension in patients with chronic liver disease.

Little evidence is available regarding the risk of hepatic decompensation (HD) after direct-acting antivirals (DAAs) in patients with advanced chronic liver disease. Our aim was to assess the risk of decompensation and the prognostic role of noninvasive tests, such as liver (LSM) and spleen (SSM) stiffness measurements, in the prediction of decompensation after sustained virologic response (SVR) by DAAs.A cohort study involving 146 cirrhotic patients treated with DAAs in our tertiary center with LSM and SSM available both before and six months after treatment (SVR24). A historical cohort of 92 consecutive cirrhotic patients with active HCV was used as a control group. A propensity score inverse probability weighting method was used to account for differences between the groups. Time-dependent models for the prediction of decompensation were applied to account for changes in noninvasive tests after therapy.The decompensation incidence in the DAA cohort was 7.07 (4.56-10.96) per 100 person-years (PYs), which was significantly lower than in the active HCV cohort. The DAA therapy was an independent protective factor for HD development (SHR: 0.071, 95 %-CI: 0.015-0.332). SSM ≥ 54 kPa was independently associated with decompensation despite SVR achievement (SHR: 4.169, 95 %-CI: 1.050-16.559), alongside with a history of decompensation (SHR: 7.956, 95 %-CI: 2.556-24.762). SSM reduction 10 % also predicted the risk of decompensation after SVR24.The risk of decompensation was markedly reduced after DAA therapy, but it was not eliminated. Paired SSM values stratified the risk of decompensation after SVR better than other noninvasive tests.ZIEL: Über das Risiko einer hepatischen Dekompensation (HD) nach direkt antiviral wirksamen Substanzen (DAA) bei Patienten mit fortgeschrittener chronischer Lebererkrankung gibt es nur wenig Evidenz. Unser Ziel war es, das Risiko einer Dekompensation und den prognostischen Wert nichtinvasiver Tests wie Messungen der Lebersteifigkeit (LSM) und Milzsteifigkeit (SSM) zur Vorhersage einer Dekompensation nach anhaltendem virologischem Ansprechen (SVR) unter DAA zu bewerten.Kohortenstudie mit 146 Zirrhose-Patienten, die in unserem Tertiärzentrum mit DAAs behandelt wurden, wobei LSM und SSM sowohl vor als auch 6 Monate nach der Behandlung verfügbar waren (SVR24). Eine historische Kohorte von 92 konsekutiven zirrhotischen Patienten mit aktiver HCV wurde als Kontrollgruppe verwendet. Um die Unterschiede zwischen den Gruppen zu berücksichtigen, wurde die Propensity-Score-Methode („inverse probability weighting“) verwendet. Zeitabhängige Modelle zur Prädiktion der Dekompensation wurden angewandt, um Veränderungen in den nichtinvasiven Tests nach Therapie zu berücksichtigen.Die Dekompensations-Inzidenz in der DAA-Kohorte betrug 7,07 (4,56–10,96) pro 100 Personenjahre (PYs), was signifikant niedriger war als in der aktiven HCV-Kohorte. Die DAA-Therapie war ein unabhängiger protektiver Faktor für die Entwicklung einer HD (SHR: 0,071; 95 %-KI 0,015–0,332). SSM ≥ 54kPa war trotz erfolgreichem SVR unabhängig mit Dekompensation assoziiert (SHR: 4,169; 95 %-KI 1,050–16,559), zusammen mit früher aufgetretener Dekompensation (SHR: 7,956; 95 %-KI 2,556–24,762). Eine SSM-Reduktion 10 % sagte auch das Risiko einer Dekompensation nach SVR24 voraus.Das Risiko einer Dekompensation war nach DAA-Therapie deutlich reduziert, aber nicht eliminiert. Gepaarte SSM-Werte stratifizierten das Risiko einer Dekompensation nach SVR besser als andere nichtinvasive Tests.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world and it is one of the main complications of cirrhosis and portal hypertension. Even in the presence of a well-established follow-up protocol for cirrhotic patients, to date poor data are available on predictive markers for primary HCC occurrence in the setting of compensated advanced chronic liver disease patients (cACLD). The gold standard method to evaluate the prognosis of patients with cACLD, beyond liver fibrosis assessed with histology, is the measurement of the hepatic venous pressure gradient (HVPG). An HVPG ≥10 mmHg has been related to an increased risk of HCC in cACLD patients. However, these methods are burdened by additional costs and risks for patients and are mostly available only in referral centers. In the last decade increasing research has focused on the evaluation of several, simple, non-invasive tests (NITs) as predictors of HCC development. We reviewed the currently available literature on biochemical and ultrasound-based scores developed for the non-invasive evaluation of liver fibrosis and portal hypertension in predicting primary HCC. We found that the most reliable methods to assess HCC risk were the liver stiffness measurement, the aspartate aminotransferase to platelet ratio index score and the fibrosis-4 index. Other promising NITs need further investigations and validation for different liver disease aetiologies.

A noninvasive diagnosis of clinically significant portal hypertension (CSPH) has important prognostic and therapeutic implications for patients with compensated advanced chronic liver disease. We aimed to validate and improve the available algorithms for the CSPH diagnosis by evaluating spleen stiffness measurement (SSM) in patients with compensated advanced chronic liver disease.This is a retrospective study including patients with liver stiffness measurement (LSM) ≥10 kPa, no previous decompensation, and available measurements of hepatic venous pressure gradient, LSM, and SSM by transient elastography referring to our center in Bologna. The diagnostic algorithms were adequate if negative and positive predictive values were90% when ruling out and ruling in CSPH, respectively; these models were validated in a cohort from Verona. The 5-year decompensation rate was reported.One hundred fourteen patients were included in the derivation cohort. The Baveno VII diagnostic algorithm (LSM ≤15 kPa + platelet count ≥150 × 10 9 /L to rule out CSPH and LSM25 kPa to rule in CSPH) was validated; however, 40%-60% of the patients remained in the gray zone. The addition of SSM (40 kPa) to the model significantly reduced the gray zone to 7%-15%, maintaining adequate negative and positive predictive values. The diagnostic algorithms were validated in a cohort of 81 patients from Verona. All first decompensation events occurred in the "rule-in" zone of the model including SSM.The addition of SSM significantly improves the clinical applicability of the algorithm based on LSM and platelet count for CSPH diagnosis. Our models can be used to noninvasively identify candidates for nonselective beta-blocker treatment and patients at a high risk of decompensation.

Background The prognostic role of spontaneous portosystemic shunts (SPSS) has been poorly investigated. Aims To evaluate the impact of the presence of SPSS, as well as their characteristics, on the risk of decompensation. Methods This is a retrospective cohort study of 235 advanced chronic liver disease (ACLD) patients with available imaging examination, transient elastography, and upper endoscopy. ACLD was defined as liver stiffness measurement (LSM) >10 kPa. Competitive risk analyses were performed to identify the factors associated with the main outcome. Results SPSS were reported in 141 (60%) of the patients. Non-viral etiology was independently associated with SPSS presence [Odds-Ratio (OR): 2.743;95%-Interval-of-Confidence (IC):1.129–6.664]. During a follow-up of 37 (20–63) months, SPSS were found predictors of any decompensation type [Subhazard Ratio (SHR):2.264; 95%-IC:1.259–4.071], independently from a history of decompensation or high-risk-varices presence. The risk of complications was higher in patients with large (SHR: 3.775; 95%-IC: 2.016–7.070) and multiple (SHR:3.832; 95%-IC: 2.004–7.330) shunts, and in those with gastrorenal shunts (SHR:2.636; 95%-IC:1.521–4.569). Conclusions The presence, size, and number of SPSS predict not only the risk of hepatic encephalopathy but that of any type of decompensation across all stages of cirrhosis. Future studies should explore the possibility of treating shunts to prevent decompensation.

(1) Background: Changes in the clinical presentation of celiac disease (CD) in children have been reported. The guidelines of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) allow esophagogastroduodenoscopy (EGD) with biopsies to be avoided under specific circumstances. We aimed to assess the clinical picture of pediatric CD patients at diagnosis and to validate ESPGHAN non-biopsy criteria. (2) Methods: Patients with suspected CD or undergoing screening from 2004 to 2014 at the University Hospital in Modena, Italy were enrolled. The accuracy of ESPGHAN non-biopsy criteria and modified versions were assessed. (3) Results: In total, 410 patients were enrolled, of whom 403 were considered for analysis. Of the patients considered, 45 were asymptomatic and diagnosed with CD (11.2%) while 358 patients (88.2%) were symptomatic, of whom 295 were diagnosed with CD. Among symptomatic CD patients, 57 (19.3%) had gastrointestinal symptoms, 98 (33%) had atypical symptoms and 140 (47.4%) had both. No difference was found for the presence of gastrointestinal symptoms at different ages. The non-biopsy ESPGHAN criteria yielded an accuracy of 59.4% with a positive predictive value (PPV) of 100%, 173 out of 308 EGD (56.2%) could have been avoided. The modified 7× and 5× upper limit of normal cut-offs for IgA anti tissue-transglutaminase reached 60.7% and 64.3% of EGD avoided, respectively. (4) Conclusions: Over 10 years, late age at diagnosis and increased rates of atypical CD presentation were found. ESPGHAN non-biopsy criteria are accurate for CD diagnosis and allow half of unneeded EGD to be avoided. Modified versions allowed sparing a greater number of EGD.

In adult patients, acute lymphoblastic leukemia (ALL) is a rare hematological cancer with a cure rate below 50% and frequent relapses. With traditional therapies, patients with relapsed or refractory (R/R) ALL have a survival that may be measured in months; in these patients, inotuzumab ozogamicin (IO) is an effective therapy. IO was linked to increased risk of veno‐occlusive disease/sinusoid obstruction syndrome (VOD/SOS), liver injury, and various grade of liver‐related complications during clinical trials and real‐life settings; however, hepatologic monitoring protocol is not established in this population. In our institution, 21 patients who received IO (median of 6 doses of IO administered) for R/R ALL were prospectively followed for hepatologic surveillance, including clinical evaluation, ultrasonography, and liver stiffness measurement (LSM) biochemistry. After a median follow‐up of 17.2 months, two SOS events were reported (both after allogeneic transplant) as IO potentially related clinically relevant adverse event. Mild alterations were reported in almost the totality of patients and moderate‐severe liver biochemical alterations in a quarter of patients. Within biochemicals value, AST and ALP showed an augment related to IO administration. LSM linearly augmented for each IO course administered. Baseline LSM was related to liver‐related changes, especially with the severity of portal hypertension (PH)‐related complications. Pre‐transplant LSM was higher in patients receiving IO when compared with a control cohort. PH‐related complications were discovered in nearly 77% of patients, with clinically significant PH occurrence and development of ascites in 38% and 14%, respectively. This prospective experience constitutes the rationale to design a hepatologic monitoring program in patients receiving IO. LSM may be of pivotal importance in this program, constituting a rapid and effective screening that quantitatively correlates with liver alterations.

Portal hypertension is the main driver of complications in patients with advanced chronic liver disease (ACLD). In the last decade, many non-invasive tests, such us liver and spleen elastography, have been proposed and validated for the identification of patients with clinically significant portal hypertension (CSPH) and its complications, mainly hepatic decompensation and liver-related morbidity and mortality. Moreover, elastography accurately stratifies for the risk of HCC development, HCC recurrence and decompensation after liver surgery. Recent studies suggest a role of SSM in monitoring response to treatments and interventions in ACLD, such as viral eradication, non-selective beta-blockers and transjugular intrahepatic portosystemic shunt placement. However, one of the most indications to perform elastography in ACLD still remains the screening for esophageal varices. In fact, according to the Baveno VIconsensus, liver stiffness measurement (LSM) 20 kPa and platelet count 150,000/mm3 can safely identify patients at low risk of varices requiring treatment (VNT) and could therefore avoid invasive upper invasive endoscopy; LSM20-25 kPa can accurately rule-in CSPH in patients with viral etiology. Spleen stiffness measurement (SSM) is a direct surrogate of portal hypertension and has been demonstrated more accurate in predicting portal hypertension severity and VNT. Acombined model including Baveno VI Criteria and SSM (46 kPa) can significantly increase the number of spared endoscopies (40-50%), maintaining a low (5%) of missed VNT.

Vascular liver disease related to portal hypertension is an exciting and not completely studied issue that includes the most common manifestations of non-cirrhotic portal hypertension, acute non-cirrhotic portal vein thrombosis (NCPVT), extrahepatic portal vein obstruction (EHPVO), and idiopathic non-cirrhotic portal hypertension (INCPH).

Introduction: Sarcopenia is defined as loss of skeletal muscle mass, strength, and function, and it is associated with increased morbidity and mortality in patients with chronic liver disease. Areas covered: The aim of this review is to provide a detailed report on the pathophysiological mechanisms underlying sarcopenia in cirrhotic patients, the several imaging methods available for the assessment of sarcopenia and the clinical studies evaluating the prognostic role of sarcopenia presence in cirrhotic patients. Expert opinion: Sarcopenia pathogenesis is complex and multifaceted, as chronic catabolic conditions, increased energy expenditure, reduced appetite, side effects of multiple therapies, alterations in circulating levels of hormones, low protein synthesis, presence of ascites or portosystemic shunts are all factors contributing to muscle atrophy in cirrhotic patients. Computed tomography scan is the most validated method to evaluate muscle mass and quality. Sarcopenia is associated with a higher rate waitlist mortality, hepatic encephalopathy, and lower quality of life in patients with liver cirrhosis. Future studies should make an effort to unify and validate liver disease-specific cutoffs for the definition of sarcopenia.

Post-hepatectomy liver failure (PHLF) is associated with great morbidity and mortality after resection of hepatocellular carcinoma. Previous studies have underlined that advanced age could be a potential factor influencing post-operative complications and long-term survival. In the past, candidates for resection were based on the Child-Pugh classification, the predictive value of which was rather low. The selection of patients undergoing resection in Western countries is based on the assessment of portal hypertension (PH), which is clinically assessed by measurement of the hepatic venous pressure gradient, an invasive and costly process. Thus, there have been several attempts to identify the best non-invasive test (NIT) to accurately predict PHLF. Most biochemical NITs for the prediction of PHLF are focused on evaluation of underlying liver cirrhosis and PH. Amongst them, FIB-4, which also includes the patient’s age, seems to have more robust supporting results. In Europe and the USA., the most tested and reliable NIT for predicting PHLF is the evaluation of liver stiffness measurement, which is also influenced by age. Imaging parameters are promising tools which are used only in specialized centers however, and when available. Liver volume parameters, as well as contrastenhanced data, demonstrate good accuracy in predicting PHLF. In this scenario, the evaluation of sarcopenia and bone mineral density through contextual imaging allows the delineation of PHLF in at-risk elderly patients. Further studies focused on parameters for the evaluation of PHLF in elderly patients are needed.

Non-selective β-blocker (NSBB) therapy is the treatment of choice for primary prophylaxis of cirrhotic patients with high-bleeding risk esophageal varices (HRV). The hemodynamic response to NSBB is assessed by the measurement of the hepatic venous pressure gradient (HVPG). Recently, liver and spleen stiffness measurements (LSM and SSM) were proposed as non-invasive surrogates of HVPG. We aimed to evaluate LSM and SSM changes for assessing hemodynamic response in these patients. Cirrhotic patients with HRV were prospectively enrolled and evaluated at our Department before starting NSBB and after 3 months. Correlation between changes (delta) of HVPG after NSBB treatment and those of LSM or SSM by transient elastography was performed. From the initial 59 patients considered for the study, 20 were finally included in the analysis. Fifteen (15) patients reached hemodynamic response to NSBB according to HVPG. Changes in LSM did not correlate with changes in HVPG (r = 0.107, p value = 0.655), unlike changes in SSM (r = 0.784, p value

Changes in body composition are associated with poor outcomes in cancer patients including hepatocellular carcinoma (HCC). Sarcopenia, defined as the loss of skeletal muscle mass, quality and function, has been associated with a higher rate of complications and recurrences in patients with cirrhosis and HCC. The assessment of patient general status before HCC treatment, including the presence of sarcopenia, is a key-point for achieving therapy tolerability and to avoid short- and long-term complications leading to poor patients’ survival. Thus, we aimed to review the current literature evaluating the role of sarcopenia assessment related to HCC treatments and to critically provide the clinicians with the most recent and valuable evidence. As a result, sarcopenia can be predictive of poor outcomes in patients undergoing liver resection, transplantation and systemic therapies, offering the chance to clinicians to improve the muscular status of these patients, especially those with high-grade sarcopenia at high risk of mortality. Further studies are needed to clarify the predictive value of sarcopenia in other HCC treatment settings and to evaluate its role as an additional staging tool for identifying the most appropriate treatment. Besides, interventional studies aiming at increasing the skeletal muscle mass for reducing complications and increasing the survival in patients with HCC are needed.

AIM To investigate changes in spleen stiffness measurements (SSMs) and other non-invasive tests (NITs) after treatment with direct-acting antivirals (DAAs) and identify predictors of SSM change after sustained virological response (SVR). METHODS We retrospectively analysed 146 advanced-chronic liver disease (ACLD) patients treated with DAA with available paired SSM at baseline and SVR24. Liver stiffness (LSM), spleen diameter (SD), platelet count (PLT) and liver stiffness-spleen diameter to platelet ratio score(LSPS) were also investigated. LSM ≥ 21 kPa was used as a cut-off to rule-in clinically significant portal hypertension (CSPH). SSM reduction > 20% from baseline was defined as significant. RESULTS SSM significantly decreased at SVR24, in both patients with and without CSPH; in 44.8% of cases, SSM reduction was > 20%. LSPS significantly improved in the entire cohort at SVR24; SD and PLT changed significantly only in patients without CSPH. LSM significantly decreased in 65.7% of patients and also in 2/3 patients in whom SSM did not decrease. The independent predictor of decreased SSM was median relative change of LSM. CSPH persisted in 54.4% patients after SVR. Delta LSM and baseline SSM were independent factors associated with CSPH persistence. CONCLUSION SSM and other NITs significantly decrease after SVR, although differently according to the patient’s clinical condition. SSM faithfully reflects changes in portal hypertension and could represent a useful NIT for the follow-up of these patients.

Background & Aims Hospitalization is associated with inadequate colon cleansing before colonoscopy. We aimed to identify factors associated to inadequate colon cleansing among inpatients, and to derive and validate a model to identify inpatients with inadequate cleansing. Methods We performed a prospective observational study at 12 hospitals in Italy. Consecutive adult inpatients scheduled for colonoscopy for any indication were enrolled from February through May 2019 (derivation cohort, n = 1016) and from June through August 2019 (validation cohort, n = 508). Inadequate cleansing was defined as Boston bowel preparation scale scores below 2 in any colon segment. We performed multivariate logistic regression to identify factors associated with inadequate cleansing. Results In the combined cohorts, 1032 patients (68%) had adequate colon cleansing. Physicians’ meetings to optimize bowel preparation (odds ratio [OR], 0.42; 95% CI, 0.27–0.65), written and oral instructions to patients (OR, 0.48; 95% CI, 0.36–0.65), admission to gastroenterology unit (OR, 0.71; 95% CI, 0.51–0.98), split-dose regimens (OR, 0.27; 95% CI, 0.20–0.35), a 1-liter polyethylene glycol-based bowel purge (OR, 0.39; 95% CI, 0.23—0.65), and 75% or more intake of bowel preparation (OR, 0.09; 95% CI, 0.05–0.15) significantly reduced odds of inadequate colon cleansing. Alternatively, bedridden status (OR, 2.14; 95% CI, 1.55–2.98), constipation (OR, 2.16; 95% CI, 1.55–3.0), diabetes mellitus (OR, 1.61; 95% CI, 1.18–2.20), use of anti-psychotic drugs (OR, 3.26; 95% CI, 1.62–6.56), and 7 or more days of hospitalization (OR, 1.02; 95% CI, 1.00–1.04) increased risk of inadequate colon cleansing. We developed a model to identify patients with inadequate cleaning using data from patients in the derivation cohort and tested it in the validation cohort. Calibration values were P = .218 for the discrimination cohort and P = .232 for the validation cohort. Discrimination values were c-statistic, 0.78 (95% CI, 0.74–0.81) for the discrimination cohort and c-statistic, 0.73 (95% CI, 0.69–0.78) for the validation cohort. We developed app for use by clinicians. Conclusions In a prospective observational study, we identified setting-, patient- and preparation-related factors that affect colon cleansing among inpatients. We derived and validated a model to identify patients with inadequate preparation and developed an app for clinicians. ClinicalTrials.gov no: NCT03925506

(1) Introduction: Liver resection (LR) for hepatocellular carcinoma (HCC) is often burdened by life-threatening complications, such as post-hepatectomy liver failure (PHLF). The albumin-bilirubin (ALBI) score can accurately evaluate liver function and the long-term prognosis of HCC patients, including PHLF. We aimed to evaluate the diagnostic value of the ALBI grade in predicting PHLF in HCC patients undergoing LR. (2) Methods: MEDLINE, Embase, and Scopus were searched through January 17th, 2021. Studies reporting the ALBI grade and PHLF occurrence in HCC patients undergoing LR were included. The Odds Ratio (OR) prevalence with 95% confidence intervals (CI) was pooled, and the heterogeneity was expressed as I2. The quality of the studies was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). (3) Results: Seven studies met the inclusion criteria and were included in the analysis. A total of 5377 patients who underwent LR for HCC were considered, of whom 718 (13.4%) developed PHLF. Patients with ALBI grades 2 and 3 before LR showed increased rates of PHLF compared to ALBI grade 1 patients. The pooled OR was 2.572 (95% CI, 1.825 to 3.626, p < 0.001), with substantial heterogeneity between the studies (I2 = 69.6%) and no publication bias (Begg’s p = 0.764 and Egger’s p = 0.851 tests). All studies were at a ‘low risk’ or ‘unclear risk’ of bias. Univariate meta-regression analysis showed that heterogeneity was not dependent on the country of study, the age and sex of the participants, the definition of PHLF used, the rate of patients in Child–Pugh class A or undergoing major hepatectomy. (4) Conclusions: In this meta-analysis of published studies, individuals with ALBI grades of 2 and 3 showed increased rates of PHLF compared to ALBI grade 1 patients.

Rationale: Inotuzumab ozagomicin (IO) has been linked to an increased incidence of veno-occlusive disease (VOD) and liver alterations. Most VOD events occurred during hematopoietic stem cell (HSCT) transplantation after IO therapy. We have previously described that the measurement of liver stiffness can anticipate the diagnosis of VOD in the context of HSCT. The mechanisms underlying the increased risk of VOD and liver damage in patients receiving IO are not well understood; in the pathogenesis endothelial damage, ozagomicin release and on-target off-tumor effects may be involved. Here, we aimed to assess the effects of IO on the changes of liver, vascular and biochemistry parameters. Methods: Intensive monitoring of the liver was incorporated into the standard of care of patients who received IO for relapsed or refractory (R / R) acute lymphoblastic leukemia (ALL). Upper abdomen ultrasound with Doppler was performed at baseline and at the end of therapy; liver stiffness measurement (LSM) by Fibroscan® (Echosens, Paris, France) at every IO course or at every IO infusion. With the exception of ursodeoxycholic acid, the patients did not receive prophylaxis for VOD. Data was collected after anonymous aggregation, in accordance with GCP and Helsinki declaration. Results are reported as median with interquartile ranges (IQR). Results: At data cut-off, 1st Apr 2019, 16 patient received baseline assessment and at least a post-IO assessment in our monitoring program. In our patent set, median age was 44.5 (IQR 30.7 - 64.0); 12/16 (75 %) patients relapsed after the last treatment and 4/16 (25 %) patients were refractory to the last treatment; patients received a median of 3 (IQR 2 - 3.7) lines before IO; 6/16 (37.5 %) patients undergone HSCT before IO, of which a patient had 1st and 2nd HSCT before IO; 5/16 (31.25 %) undergone HSCT after IO therapy (no patients had second HSCT after IO). Patients received a median of 2 (IQR 2.0 - 3.7) IO administration according to the schedule of the phase 3 trial. The median duration of the therapy was 61.5 days (IQR 43.2 - 114.0) and median progression-free survival in our population was 278.0 days (95% C.I. 264.0 - 292.0). In our patient set, we performed 113 biochemistry determination, 30 liver ultrasounds with Doppler and 116 LSM examination. One patient received a liver biopsy. Among the biochemical exams (AST, ALT, GGT and alkaline phosphatase) only the AST values significantly increased after 1st course of IO (from the median value of 21 U/L to 53 U/L after course 3). Liver ultrasound with Doppler revealed portal hypertension signs in half of the patients during IO monitoring program. Among these patients 7/16 (44%), 3/16 (17%), 5/16 (33.3%) and 3/16 (17%) showed splenomegaly, recanalization of the paraumbilical vein, dilatation of portal vein and ascites, respectively. Median LSM significantly increased from a baseline value of 6 kPa to 7.8 kPa after last post-IO assessment (p-value 7.1 kPa). With a median follow up of 387.5 days (IQR 182.8-524.5) we observed one VOD event (7%); the VOD was graded severe and occurred after HSCT post-IO. Conclusions: Our clinical experience represents the first step to better understand the IO-related liver alterations, as we described the frequency and relevance of quantitative markers. Most of the patients in our set developed ultrasound and/or elastography alteration during IO therapy. Furthermore, these alterations do not seem to correlate with biochemistry. Even if most of the patients had sub-clinical vascular and parenchymal alterations of the liver portal-hypertension related, VOD incidence in our set is comparable with literature. Long-term follow-up results are expected to test whether alterations return or evolve over time. Stratifying the tailored risk liver complications with prospective non-invasive and marker-driven strategies in term of IO dosing and HSCT timing could be a great benefit for patients. * FR and GM contributed to this manuscript equally # AC and CP contributed to this manuscript equally Figure Disclosures Martinelli: Roche: Consultancy; BMS: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; ARIAD: Consultancy. Cavo:janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau. Papayannidis:Amgen: Honoraria; Novartis: Honoraria; Teva: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Shire: Honoraria.

Background: Veno-Occlusive Disease (VOD) or Sinusoidal Obstruction syndrome (SOS), is a rare but potentially life-threatening complication after Hematopoietic Stem Cells Transplantation (HSCT). The clinical diagnosis of VOD relies on signs and symptoms, such as weight gain, painful hepatomegaly and jaundice, directly correlated to the development of sinusoidal portal hypertension (PH). It has been demonstrated that the earlier is the treatment start better the outcome. For this reason, non-invasive diagnostic tools of VOD/SOS diagnosis are needed. Ultrasound (US) Elastography techniques, assessing the Liver Stiffness Measurements (LSM), have been demonstrated to be able to assess PH degree. The role of LSM in VOD/SOS has not yet been reported in the setting of adult HSCT. Methods: We report the results of a prospective single center study evaluating the role of LSM assessed by Transient Elastography (TE), in adult patients undergoing allogeneic HSCT for haematological malignancies since April 2016 at the Institute of Hematology "L. and A. Seràgnoli", Sant'Orsola-Malpighi University Hospital, Bologna, Italy. The exclusion criteria were patients with Body Mass Index (BMI) over 40 kg/m2, ascites and diagnosis of advanced chronic liver disease (ACLD) at pre-HSCT assessment. LSM were assessed bedside of patients by TE, using the FibroScan® apparatus with "M" probe (Echosens, Paris, France), after overnight fasting and after a complete abdominal US exam, before the start of conditioning regimen and then at 3 time points after transplant (on days +9/10, +15/17 and +22/24). Results: Over the study period, among of 89 patients referred to our centre 78 patients fulfilled the inclusion criteria. Median age was 54 years (40-60). The most frequent indication was Acute Myeloid Leukemia (44.9%). 66.7% of patients received a myeloablative conditioning while 33.3% received a RIC regimen. 15.4% were transplanted from HLA identical sibling donor, 74.4% from unrelated donor, 3.8% from Haplo and 6.4% from Cord Blood. The baseline median LSM was 4.2 kPa (3.8-5.3). During the study, 4 out 78 patients (5.1%) met clinical diagnostic criteria of VOD/SOS. The median day of VOD/SOS diagnosis was +17 (+1 - +29). Most of the VOD/SOS were Severe/Very severe (3/4), one of them leading to Multiple Organ Failure and death. Accordingly with EBMT criteria, the total number of pre-HSCT VOD/SOS risk factor was significantly higher in patients who developed VOD/SOS. We also valuated the US signs, according to Lassau criteria, in patients with VOD/SOS: 3 out 4 patients had ≥3 Grey-scale US morphologic Criteria and none presented ≥3 US Colour Doppler Criteria. Only portal vein diameter >12 mm was presented in all patients with VOD/SOS diagnosis. LSM values for each time points were reported in Figure 1; LSM by TE showed increased values in all patients who developed VOD/SOS (red continuous lines). Pre-HSCT (T0) LSM tended to be slight (p-value 0.079) higher (6.9 kPa vs 4.2 kPa) in patients who developed VOD/SOS. In these patients, the LS values increased before VOD/SOS clinical diagnosis, with values significantly different from pre-HSCT and from the previous assessments, anticipating from 2 to 12 days the clinical VOD/SOS development. After starting VOD/SOS specific treatment (defibrotide and diuretics) LSM values consensually decreased to pre-transplant values within 2-4 weeks. In univariate analysis an LSM increase after HSCT was significantly associated with VOD/SOS development (OR: 1.837; 95%CI [1.1107- 3.0384], p Interpretation: LSM by TE showed significantly increased values in all patients who developed VOD/SOS, anticipating by some days the clinical criteria for VOD/SOS diagnosis. By our knowledge this is the first prospective study focused on the use of LSM for early prediction of VOD/SOS. Further validation of these data are warranted to confirm the diagnostic role and the predictive value of LSM in the VOD/SOS development. Figure 1. Figure 1. Disclosures Zinzani: Takeda: Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Speakers Bureau; MSD: Honoraria, Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cavo:GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.