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Sarcopenia is gaining attention as a negative prognostic factor in different fields of medicine, including chronic liver failure. However, the assessment of sarcopenia in patients with liver diseases is often neglected due to unawareness of reliable tools and methods and thus is limited to research studies. Cross-sectional imaging is a diffuse diagnostic tool and is commonly performed in patients with chronic liver failure. The last advancements in radiology image analysis using dedicated software allow an easy and standardized method to assess skeletal muscle volume. Several measures can be obtained from cross-sectional imaging analysis to evaluate sarcopenia in patients affected by chronic liver disease. We aimed to review the recent advances in imaging-based sarcopenia assessment, in particular in patients with chronic liver diseases. As a result, we found that the skeletal muscle index (SMI) seems to be a reliable method to assess sarcopenia in cirrhotic patients. Even if further studies are needed to validate proper cut-offs for each clinical endpoint, physicians are invited to consider the assessment of sarcopenia in the work-up of patients with chronic liver disease.

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BACKGROUND & AIMS Based on platelets and liver stiffness measurements, the Baveno VI criteria (B6C), the expanded B6C (EB6C), and the ANTICIPATE score can be used to rule out varices needing treatment (VNT) in patients with compensated chronic liver disease. We aimed to improve these tests by including data on the ratio of platelets to liver stiffness. METHODS In a retrospective analysis of data from 10 study populations, collected from 2004 through 2018, we randomly assigned data from 2368 patients with chronic liver disease of different etiologies to a derivation population (n = 1579; 15.1% with VNT, 50.2% with viral hepatitis, 28.9% with nonalcoholic fatty liver disease, 28.9% with alcohol-associated liver disease, 20.8% with model for end-stage liver disease scores of 9.5 ± 3.0, and 93.0% with liver stiffness measurements ≥10 kPa) or a validation population (n = 789). Test results were compared with results from a sequential algorithm (VariScreen). VariScreen incorporated data on platelets or liver stiffness measurements and then the ratio of platelets to liver stiffness measurement, adjusted for etiology, patient sex, and international normalized ratio. RESULTS In the derivation population, endoscopies were spared for 23.9% of patients using the B6C (VNT missed in 2.9%), 24.3% of patients using the ANTICIPATE score (VNT missed in 4.6%), 34.5% of patients using VariScreen (VNT missed in 2.9%), and 41.9% of patients using the EB6C (VNT missed in 10.9%). Differences in spared endoscopy rates were significant (P ≤ .001), except for B6C vs ANTICIPATE and in missed VNT only for EB6C vs the others (P ≤ .009). VariScreen was the only safe test regardless of sex or etiology (missed VNT, ≤5%). Moreover, VariScreen secured screening without missed VNT in patients with model for end-stage liver disease scores higher than 10. This overall strategy performed better than a selective strategy restricted to patients with compensated liver disease. Test performance and safety did not differ significantly among populations. CONCLUSIONS In a retrospective study of data from 2368 patients with chronic liver disease, we found that the B6C are safe whereas the EB6C are unsafe, based on missed VNT. The VariScreen algorithm performed well in patients with chronic liver disease of any etiology or severity-it is the only test that safely rules out VNT and can be used in clinical practice.

Summary. Portal hypertension (PH) is the main driver of complications in patients with advanced chronic liver disease (ACLD). Correctly identifying the presence and severity of PH is crucial for the management and prognosis of compensated ACLD (cACLD) patients. Over the last 20 years, several non-invasive tests (NITs) have been proposed for PH assessment; among these, liver (LSM) and spleen (SSM) stiffness measurement by transient elastography are the most validated and accurate predictors of clinically significant PH (CSPH) and its complications, such as gas-troesophageal varices, clinical decompensation and hepatocellular carcinoma. The inclusion of NITs in the official recommendations of the Baveno VI Consensus, as valid and trustworthy tools to assess PH in cACLD patients, represents one of the major advances in hepatology of the last years. For instance, the recently proposed Baveno VI Criteria (LSM150×109/L) have proven to be a valid strategy to rule out the presence of high-risk varices (HRV) and identify patients that can safely avoid screening upper endoscopy (EGD). In conclusion, further studies are necessary to fully explore the potential of NITs and maximize their use in everyday clinical practice.

Gut microbiota is a complex ecosystem, resident in the digestive tract, exerting multiple functions that can have a significant impact on the pathophysiology of the host organism. The composition and functions of this "superorganism" are influenced by many factors, and among them, the host's dietary habits seem to have a significant effect. Dietary changes in the evolution of human history and in the different stages of life of the human subjects are responsible for qualitative and functional modification of gut microbiota. At the same time, the different dietary models adopted in worldwide geographic areas take into account the inter-individual differences concerning composition and microbial function. This close relationship between diet, gut microbiota and host seems, in fact, to be responsible for the protection or predisposition to develop several metabolic, immunological, neoplastic and functional diseases. Thus, several studies have evaluated the impact of diet and lifestyle modification strategies on gut microbiota composition and functions which, in turn, seems to affect the effectiveness of such therapeutic measures. Gut microbiota manipulation strategies, as complementary to dietary modifications, represent a fascinating field of research, even if consolidated data are still lacking.

The assessment of portal hypertension is a relevant step in the evaluation of newly diagnosed advanced chronic liver disease (ACLD). The current gold standard includes the invasive evaluation of hepatic venous pressure gradient (HVPG) and endoscopy. However, noninvasive or minimally invasive techniques to assess portal hypertension have been proposed and well established. In the present manuscript, we review clinical studies on the use of noninvasive or minimally invasive techniques to assess portal hypertension in ACLD patients.

L’encefalopatia epatica (EE) costituisce una frequente complicanza della malattia cronica del fegato, che si può manifestare con un ampio spettro di anomalie neurologiche/psichiatriche che vanno da alterazioni subcliniche al coma. In accordo con le più recenti linee-guida, l’EE può essere classificata in differenti tipi, a seconda della severità dell’insufficienza epatica, della presenza di shunt porto-sistemici e del numero di episodi pregressi o della persistenza del quadro clinico. Da un punto di vista clinico, i quadri di EE posso essere definiti come non alterato, nascosto (che comprende due condizioni, l’EE minima e quella di grado 1, secondo la classificazione che valuta il grado di coinvolgimento mentale) e quello manifesto (che presenta tre gradi di impegno mentale). I meccanismi patogenetici alla base delle differenti forme di EE sono complessi e numerosi, per es. il ruolo dell’ammonio, di citochine pro-infiammatorie, di composti simil-benzodiazepine e l’accumulo di manganese. Nel tempo sono state proposte e attuate differenti strategie terapeutiche per l’EE, in particolare per la forma manifesta, dal momento che la gestione dell’EE nascosta richiede una valutazione caso per caso. Momento fondamentale della gestione del paziente con EE è rappresentato dalla ricerca e dall’eventuale riconoscimento con conseguente trattamento dei fattori scatenanti. I trattamenti più efficaci, che possono essere effettuati singolarmente o in combinazione, sono rappresentati dai disaccaridi lattulosio e lattitolo e dall’antibiotico topico rifaximina. Ulteriori composti utilizzati nel trattamento della EE, in particolare nei casi non responsivi, sono rappresentati dagli aminoacidi ramificati e da composti in grado di favorire l’eliminazione dell’ammonio Hepatic encephalopathy (HE) is a common complication of liver cirrhosis and it can manifest with a broad spectrum of neuropsychiatric abnormalities of varying severity, acuity and time course with important clinical implications. According to recent guidelines, HE has been classified into different types, depending on the severity of hepatic dysfunction, the presence of porto-systemic shunts and the number of previous episodes or persistent manifestations. From a clinical point of view, HE can be recognized as unimpaired, covert (that deals with minimal and grade 1 according to the grading of mental state), and overt (that is categorized from grade 2 to grade 4). Different and only partially known pathogenic mechanisms have been identified, comprising ammonia, inflammatory cytokines, benzodiazepine-like compounds and manganese deposition. Different therapeutic strategies are available for treating HE, in particular the overt HE, since covert HE needs to be managed case by case. Recognition and treatment of precipitating factors represent fundamental part of the management. The more effective treatments, which can be performed separately or combined, are represented by non-absorbable disaccharides (lactulose and lactitol) and the topic antibiotic rifaximin; other possible therapies, mainly used in patients non responders to previous treatments, are represented by branched chain amino acids and metabolic ammonia scavengers.

Purpose: Liver stiffness (LS) has been shown to be of use in chronic liver disease patients but its utility in surgical judgment still needs to be proven. A decision-making approach was applied to evaluate whether LS measurement before surgery of hepatocellular carcinoma (HCC) can be useful in avoiding post-hepatectomy liver failure (PHLF). Materials and Methods: Decision curve analysis (DCA) was applied to 202 HCC patients (2008?–?14) with LS measurement prior to hepatectomy to verify whether the occurrence of PHLF grades B/C should be reduced through a decision-making approach with LS. Results: Within 90 days of surgery, 4 patients died (2?%) and grades B/C PHLF occurred in 29.7?% of cases. Ascites and/or pleural effusion, treatable with medical therapy, were the most frequent complications. DCA showed that using the “expected utility theory” LS measurement can reduce up to 39?% of cases of PHLF without the exclusion of any patient from surgery that duly undergoes an uncomplicated postoperative course. LS measurement does not add any information to normal clinical judgment for patients with a low (10?%) risk of PHLF. Conclusion: LS measurement can determine a reduction of PHLF under “expected utility theory” fulfilment. However, the degree of PHLF can be minor and “risk seeking” individuals can accept such a risk on the basis of surgical benefits.

The use of patient’s diaries in Gastroenterology In the diagnostic and therapeutic work-up, which represents a relevant component of the complex patient-doctor relationship, the listening and understanding by the doctor of the patient’s personal and medical history is crucial. However, this communicative moment may be difficult and misleading for several reasons, e.g. the inability of the patient to fully recall his symptoms, but also difficulties for the doctor to understand the timely evolution of the clinical picture and its relationship with the daily activities. Research has shown that patient recall of symptoms is unreliable, possibly showing inaccuracies and biases. Recognition of recall's shortcomings has led to the use of diaries, which are intended to capture experiences close to the time of occurrence, thus limiting recall bias and producing more accurate data. Furthermore, clinical diaries represent a way for the patient to assess his own health status without clinician bias or interpretation. Self-reported diaries are also useful tools for both researchers and clinicians in collecting numerous subjective and behavioural variables relevant to research and clinical practice. Diaries have been used in different clinical conditions, such as to measure pain, sleep, coping with smoking urges, illness or injury and health care use, medication taking, exercise, eating-related behaviours. Different types of diaries are available and have been tested in clinical practice: paper-and-pencil and electronic diaries. The available literature regarding both the systematic reviews and the comparative studies has identified the main limits of the paper-and-pencil diaries: the patient’s literacy, the time to complete the daily diaries, the social acceptability of self-monitoring in public situation, the difficulties in determining when the diary is completed; beside the main limitation for electronic diaries is represented by the technical functioning and use of the device. Gastrointestinal diseases represent a field where the patient’s diary could have an important role not only in the patient-doctor relationship, but also in the overall clinical management. In fact the recognition and measurement of gastrointestinal symptoms is subject to several difficulties. This is particularly true in patients with functional dyspepsia or irritable bowel syndrome, very frequent conditions since they affect 20-40% of adults in the western world, whose definition is based on only clinical parameters. In fact functional dyspepsia is defined as a pain, or discomfort, localized at the epigastrium, with possibly associated symptoms such as postprandial fullness or heartburn, while irritable bowel syndrome is characterized by an abdominal pain, or discomfort, associated with a change in stool frequency or form. Since there are no biological markers for these two pathological conditions, clinical studies rely entirely on patient’s diary. Furthermore, since in most cases symptoms are related, if not induced, by food ingestion, it is very important, from a diagnostic and therapeutic point of view, to identify the possible causative role of nutrient/s in inducing abdominal symptoms. Dietary recall is a widely used diagnostic tool, with two main indications: to self-monitor one’s eating behaviour and food consumption on a daily basis as a part of an intervention and to record in detail all foods consumed for a computerized nutrient analysis for outcome assessment. In fact self-monitoring food intake is considered the cornerstone of behavioural treatment of obesity and other chronic disorders that can be managed by dietary modification and control, such as diabetes, dylipidemia and end stage renal disease. Also in this field, most of the available studies have compared different types of diaries, e.g. paper-based or digital based (for recording food intake: computerized assessment, personal digital assistants, digital photography and small cards) and most frequently they deal separately with clinical symptoms and food intake. On the contrary, the ideal condition could be represented by the simultaneous presence, in the self-reported diary, of both the symptoms occurring in the daily life and the nutrient assumption. However, very few studies have been performed using this type of diary in patients with functional gastrointestinal diseases. In the present chapter a critical analysis of the data actually available and a proposal for future studies will be performed.

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of α-interferon (IFNα) alone to the combination of IFNα plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNβ represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNβ treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNβ are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNβ treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported. A more recent study, performed to compare IFNβ alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-1b HCV hepatitis unresponsive to IFNα treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNβ and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.

L'articolo esamina i processi di riforma delle libere professioni italiane focalizzando l'attenzione sul DPR 137/12, comparando il campo giuridico con quello sanitario e analizzando il ruolo amrginale che la nuova legislazione affida all'università.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is becoming one of the most common causes of chronic liver disease worldwide. The economic and social cost of disease is very high and there is a need for effective treatments. Areas covered: The available and potential future treatments for NAFLD are reviewed. Expert opinion: Weight loss remains the cornerstone of treatment of hepatic steatosis, but difficult to pursue. A pragmatic approach relies on generic recommendations for weight loss and physical activity in the whole population and limiting interventions to subject at risk of disease progression, but the type of preferred treatment remains a matter of debate. The large number and mechanistic diversity of drugs that have so far been investigated bear testimony to the lack of a specific, effective agent. Insulin resistance remains the pivotal alteration responsible for liver disease and its progression and insulin sensitizers are regarded as the treatment of choice. Several ongoing studies are testing the effectiveness of new approaches on histological outcomes and new metabolic pathways are under scrutiny.

Analizza il rapporto tra formazione universitaria e mondo professionale

The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined.To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta.Forty-three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real-time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data.Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P0.001 and P0.01, respectively). MRP3 protein expression was not significantly different between the groups while RNA expression was significantly decreased in treated patients (P0.01). MRP4 did not show significant differences between the groups.Ursodeoxycholic acid administration induces placental MRP2 expression, and reduces bilirubin and bile acid levels in cord blood.

Principali quadri ecografici della patologia colecistica

The nuclear receptor PPAR-alpha (Peroxisome proliferator-activated receptor-alpha) regulates the transcription of genes involved in fatty acid and bile acid metabolism and transport. PPAR-alpha is activated following binding with natural (fatty acids) or exogenous (fibrates) ligands. A common polymorphism in the PPAR-alpha gene (PPARA) is a functional missense mutation which causes a leucine to valine substitution (L162V). Another frequent polymorphism is a G to C transversion in intron 7. In order to test the etiopathogenic relevance of PPARA polymorphisms in gallstone disease, we investigated the prevalence of exon 5 and intron 7 variants, either isolated or in combination, in gallstone patients and in a control population. One hundred and twenty seven gallstone patients (56 males, 71 females) admitted to the hospital for either elective cholecystectomy or endoscopic treatment of choledocolithiasis, were screened for the presence of PPARA polymorphisms. Control population was composed of 110 age matched hospital workers and university students (53 males, 57 females). After DNA extraction from peripheral blood leukocytes, PCR amplification of exon 5 and intron 7 was performed. Denaturing-high performance liquid chromatography (D-HPLC) was then used to screen the PCR products for the presence of polymorphisms. Automated sequencing was employed to confirm and characterize the polymorphisms. Statistical analysis was performed by the chi-square test. The overall carrier frequency of exon 5 L162V polymorphism was 11% in the control population and 13.4% in the gallstone group (p=NS). The total carrier frequency for intron 7 polymorphism was 25% in the control population, while in male and female lithiasic patients it was 43% and 37%, respectively (p= 0.03). The haplotype characterized by exon 5 L162V, in the absence of intron 7 polymorphism, was not found in males with gallstones, while a 11% frequency was observed in male controls (p=0.02). These data demonstrate a significant higher prevalence of PPARA intron 7 polymorphism in gallstone patients, mainly due to its frequency in the male subgroup. Furthermore, the haplotype characterized by exon 5 L162V, in the absence of an associated intron 7 polymorphism, seems to confer protection from gallstones in males but not in females, supporting an hormone modulation on PPAR-alpha polymorphic variants.

Il capitolo approfondisce i seguenti argomenti: -impatto dei fenomeni migratori sulla diffusione delle infezioni ed infestazioni a carico dell'apparato digerente; -cause di infezioni ed infestazioni gastrointestinali; - principali sintomi clinici delle infezioni ed infestazioni gastrointestinali; -strumenti diagnostici utili per la diagnosi di infezione ed infestazione gastrointestinale -indirizzi terapeutici nei confronti delle principali infezioni ed infestazioni gastrointestinali. dei fenomeni migratori sulla diffusione delle infezioni ed infestazioni

Background and aims: We aimed to improve non-invasive screening of varices needing treatment (VNT) and compare different screening strategies. Methods: 2,290 patients with chronic liver disease were included in a retrospective study. Etiologies were: virus: 50.0%, NAFLD: 29.5%, alcohol: 20.5%, VNT: 14.9%. Test descriptors were performance (spared endoscopy) and safety (missed VNT). VNT tests were evaluated according to their safety levels either for individual screening (95% negative predictive value (NPV)), population screening (95% sensitivity) or undifferentiated screening (100% sensitivity/NPV) without missed VNT. The tests provided three categories: missed VNT

Background & Aims Hepatocellular carcinoma (HCC) is a frequent complication of liver disease. When feasible, hepatic resection is the first-choice therapy. However, tumor recurrence complicates at least 2/3 hepatic resections at 5 years. Early recurrences are mainly tumor or treatment-related, but predictors of late recurrences are undefined. We aimed to evaluate the factors related to HCC recurrence after curative resection, with liver and spleen stiffness measurement (LSM and SSM) as markers of severity and duration of the underlying liver disease. Methods We enrolled patients with chronic liver disease and primary HCC suitable for hepatic resection. We followed up patients for at least 30 months or until HCC recurrence. We performed uni- and multivariate analyses to evaluate the predictive role of tumor characteristics, laboratory data, LSM and SSM for both early and late recurrence of HCC. Results We prospectively enrolled 175 patients. Early HCC recurrence at multivariate analysis was associated with viral etiology, HCC grading (3 or 4), resection margins Conclusions SSM seems to be the only predictor of late HCC recurrence, since it is directly correlated with the degree of liver disease and portal hypertension, both of which are involved in carcinogenesis. Lay summary The main result of this study is that spleen stiffness measurement, evaluated by transient elastography, seems to be the only predictor of the late recurrence of hepatocellular carcinoma, defined as recurrence after 24 months from liver resection. Indeed, spleen stiffness measurement is directly correlated with the degree of liver disease and portal hypertension, which are both involved in carcinogenesis.

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

Veno-occlusive-disease(VOD),also known as sinusoidal-obstruction-syndrome(SOS), is one of the main complications of hematopoietic stem cell transplantation and is related to the treatment with pyrrolizidine alkaloids or other toxic agents. Clinical diagnosis using the new criteria is the reference for SOS/VOD diagnosis. Increasing evidence suggests the emerging role of several imaging methods that could help the clinician in VOD/SOS assessment. The survival rate is higher when earlier specific therapy is initiated,improving early, non-invasive diagnosis of SOS/VOD is strongly needed.We aimed to assess in patients undergoing HSCT, the SOS/VOD diagnostic role of Liver Stiffness Measurement (LSM) evaluated by elastography techniques. The ElastoVOD project was an interventional study without drugs developed in two sequential phases:the first was monocentric proof of the concept study in Bologna from April 2015 to November 2017; the second was a national multicentre study involving around 47 Italian transplant centres and is still ongoing (clinicaltrial.govNCT03426358). LSM was performed before HSCT and at day +9/10, +15/17 and +22/24 post-HSCT. EBMT-criteria were used to establish a VOD/SOS diagnosis. Among the 456 patients undergoing HSCT, 20 patients developed SOS/VOD (4.4%) during the study period. A sudden increase of LSM, compared to the previous assessment and pre- HSCT measurement, was found in all patients who developed SOS/VOD. LSM increases occurred from 1 to more than ten days before clinical SOS/VOD appearance. The SOS/VOD diagnostic performance of increased LSM over pre-HSCT assessment showed AUROC 0.997 (Sens.75%Spec.98.7%). LSM gradually decreased following successful SOS/VOD specific treatment. Interestingly in the adult patient’s subgroup, LSM values did not significantly increase in patients experiencing hepato-biliary complications other than SOS/VOD. Elastography techniques measuring LSM represent the most recent and promising approach to perform an early, pre-clinical diagnosis and follow-up of SOS/VOD. In our view, a multidisciplinary approach to the SOS/VOD diagnosis should be highly encouraged.

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm worldwide. Recurrence of HCC after resection or loco-regional therapies represents an important clinical issue as it affects up to 70% of patients. This can be divided into early or late, if it occurs within or after 24 months after treatment, respectively. While the predictive factors for early recurrence are mainly related to tumour biology (local invasion and intrahepatic metastases), late recurrences are mainly related to de novo tumour formation. Thus, it is important to recognize these factors prior to any treatment in each patient, in order to optimize the treatment strategy and follow-up after treatment. The aim of this review is to summarize the current evidence available regarding predictive factors for the recurrence of HCC, according to the different therapeutic strategies available. In particular, we will discuss the role of new ultrasound-based techniques and biological features, such as tumor-related and circulating biomarkers, in predicting HCC recurrence. Recent advances in imaging-related parameters in computed-tomography scans and magnetic resonance imaging will also be discussed.

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: Baveno VI criteria enabled the screening of varices needing treatment (VNT) without endoscopy but created confusion by not stating the method used to calculate the 5% missed VNT limit, resulting in different calculations across validation studies. We analysed those calculations to clarify their diagnostic meaning. Methods: (a) Literature review and recalculation of the missed VNT rates according to the three definitions encountered. (b) Contingency table comparison of these latter to determine their diagnostic meanings. (c) Real case analysis. 4/Simulation of variations in the three main statistical descriptors (VNT, missed VNT or spared endoscopies). Results: Missed VNT rates in the three definitions varied five- to 10-fold across 7 papers. The contingency table showed that the definitions based on VNT prevalence and spared endoscopy as reference corresponded, respectively, to sensitivity and negative predictive value (NPV). The whole population-based definition corresponded to diagnostic accuracy (not pertinent in that setting). Real case analysis showed that concerning liver stiffness, the 95% sensitivity and NPV cut-offs for VNT were, respectively, 14.1 and 26.5 kPa. The VNT-based definition offered a more statistically powerful paired comparison between diagnostic tests, whereas the definition based on spared endoscopies was hampered by an unpaired comparison. Case simulation showed that the VNT-based definition was the most sensitive to descriptor variations. Conclusion: The definitions of missed VNT rate placing VNT or spared endoscopy as the denominator are appropriate, providing, respectively, sensitivity and NPV for VNT. We privilege the first since it corresponds to the true proportion of missed VNT.

Aims. Budd-Chiari Syndrome (BCS) is a rare vascular disease of the liver caused by the obstruction of the hepatic venous outflow located from the small hepatic venules up to the entrance of the inferior vena cava (IVC) into the right atrium. Current prognostic indexes are suboptimal for an individual prognostic assessment and subsequent management of patients with BCS. Liver (LSM) and spleen (SSM) stiffness measurements are widely validated prognostic tools in hepatology, but the evidence in patients with BCS is limited. This paper describes LSM and SSM in patients with BCS and their correlation with clinical, biochemical, and ultrasound findings from the same patients. Methods. We investigated a case series of seven patients with BCS diagnosis and available LSM and SSM evaluated by transient elastography (TE). Biochemical, imaging, and endoscopic findings nearest to the TE evaluation were recorded. Clinical outcomes and BCS evolution were described for each patient. When available, repeated TE assessments were also recorded. Results. Patients with acute nonfulminant manifestation of BCS presented near-the-upper-limit values (75 kPa) of LSM and SSM, which often persist until the placement of a transjugular intrahepatic portosystemic shunt (TIPS). On the other hand, TE values were markedly lower in patients with compensated BCS. In some patients with repeated TE measurement years after TIPS placement, LSM had decreased to values of Conclusions. Extremely elevated values of LSM and SSM are suggestive of BCS. The evaluation of both LSM and SSM by TE could help clinicians in the initial evaluation, risk stratification, and therapy response monitoring of patients with BCS.

To perform a systematic review with meta-analysis to assess whether ultrasound elastography can have a diagnostic role in detecting fibrotic bowel strictures in patients with Crohn's disease. MEDLINE via the PubMed, Ovid Embase, Scopus and Cochrane Library databases, and abstracts of international conference proceedings were searched up to March 31, 2018. Studies were included if they assessed the performance of abdominal ultrasound elastography in detecting fibrotic bowel strictures in patients with Crohn's disease using histology or the need for surgery after medical treatment as a reference standard. The quality of the studies was assessed using Quality Assessment of Diagnostic Accuracy Studies. 6 studies including a total of 217 patients with Crohn's disease and 231 bowel segments, of which 76 were bowel segments with fibrotic stricture, were selected. Three studies used strain ratio and three studies used strain value as parameters of bowel stiffness. Both the pooled standardized mean strain ratio and the pooled standardized mean strain value were higher in bowel segments with fibrotic strictures than in those without fibrotic strictures with a standardized mean difference of 0.85 (95 % confidence level [CI]: 0 to 1.71; p = 0.05) and 1.0 (95 % CI: -0.11 to 2.10; p = 0.08), respectively. There was a high heterogeneity between studies. All studies were at "high risk" or "unclear risk" of bias. Ultrasound elastography could be able to detect fibrotic bowel strictures in patients with Crohn's disease. Well-designed high quality diagnostic studies with a large sample size are needed.ZIEL: Durchführung eines systematischen Reviews mit Meta-Analyse, um zu beurteilen, ob Ultraschall-Elastografie eine diagnostische Rolle beim Erkennen fibrotischer Darmstrikturen bei Patienten mit Morbus Crohn spielen kann. Es wurden MEDLINE über die Datenbanken PubMed, Ovid Embase, Scopus und Cochrane Library sowie die Abstracts aus den Tagungsbänden internationaler Konferenzen bis zum 31. März 2018 durchsucht. Aufgenommen wurden Studien, wenn sie die Leistung der abdominalen Ultraschall-Elastografie bezüglich der Erkennung fibrotischer Darmstrikturen bei Patienten mit Morbus Crohn bewerteten und wenn als Referenzstandard eine histologische Untersuchung oder eine notwendige Operation im Anschluss an medizinische Behandlung durchgeführt wurde. Die Qualitätsbeurteilung der Studien erfolgte mittels QUADAS („Quality Assessment of Diagnostic Accuracy Studies“). 6 Studien wurden ausgewählt, die insgesamt 217 Patienten mit Morbus Crohn und 231 Darmsegmente, darunter 76 Darmsegmente mit fibrotischer Striktur, einschlossen. 3 Studien verwendeten die Strain-Ratio und die 3 anderen den Strain-Value als Parameter für die Darmsteifigkeit. Sowohl die gepoolte standardisierte mittlere Strain-Ratio als auch der gepoolte standardisierte mittlere Strain-Value waren in Darmsegmenten mit fibrotischen Strikturen höher als in solchen ohne fibrotische Strikturen. Die standardisierte Mittelwertdifferenz betrug mit fibrotischen Strikturen 0,85 (95 % Konfidenzniveau [CI]: 0 bis 1,71; p = 0,05) und ohne Strikturen 1,0 (95 % CI: –0,11 bis 2,10; p = 0,08). Es gab eine große Heterogenität zwischen den Studien. Alle Studien hatten ein „hohes" oder „nicht eindeutiges Risiko“ für Bias. Die Ultraschall-Elastografie könnte fibrotische Darmstrikturen bei Patienten mit Morbus Crohn nachweisen. Erforderlich sind gut konzipierte, qualitativ hochwertige Diagnosestudien mit ausreichender Stichprobengröße.

Background: Colonic diverticulosis is a common condition in industrialized countries. Up to 25% of patients with diverticula develop symptoms, a condition termed symptomatic uncomplicated diverticular disease (SUDD). The aim of the present study was to characterize neuroimmune interactions and nerve fiber plasticity in the colonic mucosa of patients with diverticula. Methods: Controls, patients with diverticulosis and with SUDD were enrolled in the study. Mucosal biopsies were obtained close to diverticula (diverticular region) and in a normal mucosa (distant site), corresponding to sigmoid and descending colon in the controls. Quantitative immunohistochemistry was used to assess mast cells, T cells, macrophages, nerve fibers, and neuronal outgrowth (growth-associated protein 43, GAP43+fibers). Key Results: No difference emerged in mast cells and T cells among the three groups. Macrophages were increased in patients with SUDD and diverticulosis as compared to controls. Nerve fibers were enhanced in patients with SUDD and diverticulosis in comparison with controls in the diverticular region. GAP43+fibers were increased only in patients with SUDD as compared to controls and to patients with diverticulosis in the diverticular region. In patients with SUDD, GAP43 density was increased in the diverticular region compared to distant site. Macrophages close to GAP43+ fibers were increased in the diverticular region of patients with SUDD. Significant correlations were found between GAP43+ fibers and immune cells. Conclusions and Inferences: Patients with diverticula are characterized by increased macrophage counts, while nerve fiber sprouting is increased only in the diverticular region of patients with SUDD suggesting a role in symptom generation.

none 13 no Published Online First: 12 September 2016 OBJECTIVE: The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study. DESIGN: Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls. Mucosal immunocytes, in the diverticular region and in unaffected sites, were quantified with immunohistochemistry. Mucosa and faecal microbiota were analysed by the phylogenetic platform high taxonomic fingerprint (HTF)-Microbi.Array, while the metabolome was assessed by 1H nuclear magnetic resonance. RESULTS: Compared with controls, patients with diverticula, regardless of symptoms, had a >70% increase in colonic macrophages. Their faecal microbiota showed depletion of Clostridium cluster IV. Clostridium cluster IX, Fusobacterium and Lactobacillaceae were reduced in symptomatic versus asymptomatic patients. A negative correlation was found between macrophages and mucosal Clostridium cluster IV and Akkermansia. Urinary and faecal metabolome changes in diverticular disease involved the hippurate and kynurenine pathways. Six urinary molecules allowed to discriminate diverticular disease and control groups with >95% accuracy. CONCLUSIONS: Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease. Barbara, Giovanni; Scaioli, Eleonora; Barbaro, Maria Raffaella; Biagi, Elena; Laghi, Luca; Cremon, Cesare; Marasco, Giovanni; Colecchia, Antonio; Picone, Gianfranco; Salfi, Nunzio; Capozzi, Francesco; Brigidi, Patrizia; Festi, Davide Barbara, Giovanni; Scaioli, Eleonora; Barbaro, Maria Raffaella; Biagi, Elena; Laghi, Luca; Cremon, Cesare; Marasco, Giovanni; Colecchia, Antonio; Picone, Gianfranco; Salfi, Nunzio; Capozzi, Francesco; Brigidi, Patrizia; Festi, Davide

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