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P001 Bowel sonography in predicting post-operative course of Crohn’s disease F. Castiglione1 *, A. Testa1, F. Sabbatini1, L. Bucci2, G. Pesce3, G.D. De Palma4, M. Diaferia1, N. Caporaso1, A. Rispo1. 1Gastroenterology University Federico II, Naples, Italy, 2Surgery University Federico II, Naples, Italy, 3Emergency Surgery University Federico II, Naples, Italy, 4Surgery and Advanced Technologies University Federico II, Naples, Italy

The aim of the present study was to evaluate whether hepatitis C virus plays any role in the development of hepatocellular carcinoma in cirrhotic patients. The role of age, sex, alcohol abuse, and infection by other hepatitic viruses, such as hepatitis B and Delta viruses, was also assessed. We found that mean age and male/female ratio were significantly higher in patients with HCC plus liver cirrhosis than in those with liver cirrhosis alone. Also, the prevalence of HCV infection was found to be higher in HCC patients compared to cirrhotics. Further, by means of multiple logistic regression, we evaluated the independent role of each variable in the development of HCC. Age, male sex, and to a lesser degree, HCV infection, as assessed by anti-HCV positivity, were the only risk factors which significantly correlated with the development of HCC. Moreover, when age and sex were excluded from the statistical model, HCV infection, but not HBV, HDV, and alcohol abuse, appeared to be associated with HCC. In conclusion, based on these data, age and male sex are the most important factors for the development of hepatocellular carcinoma in cirrhotic patients. Hepatitis C virus, at least in the Mediterranean area, may play a role as an additive risk factor of HCC in patients suffering from liver cirrhosis.

This study was undertaken to evaluate the effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients. Sixteen cirrhotics were randomly assigned to metoclopramide (10 mg i.v.) or saline. Metoclopramide significantly decreased transmural variceal pressure (15.7% decrease, p less than 0.05 vs. basal value). In order to evaluate if the metoclopramide-induced drop in transmural variceal pressure was due to an effect on portal haemodynamics, we also measured, by means of real time and pulsed Doppler ultrasonography, portal vein diameter, mean velocity of portal flow, and portal venous flow. No significant change was observed before and after metoclopramide. In conclusion, metoclopramide, which increases lower oesophageal sphincter pressure, significantly decreases transmural variceal pressure in cirrhotic patients. However, it does not have any effect on portal haemodynamics.

Quite often patients affected by chronic HCV infection show no clinical signs of liver disease and display persistently normal aminotransferase values. These patients, defined “healthy or asymptomatic carriers,” can have active viral replication and various degrees of histological liver damage. Aim: To verify, in a population of healthy anti-HCV-positive carriers, if the aminotransferases of viremics (although in the normal range) are considerably different from those of non viremics. Patients and Methods: We followed 26 healthy anti-HCV-positive subjects (17 HCV-RNA+ and 9 HCV-RNA-) by determining ALT and AST at 3-month intervals for an average of 2.6 years (range l-4). Results: During the entire follow-up, aminotransferases persistently remained in the normal range on all samples (237 testings: 150 HCV-RNA+ and 87 HCV-RNA-). The ALT mean was 0.618 t0.171 x maximum normal value (MNV) and 0.434 k 0.153 x MNV respectively in the HCV-RNA+ and in the HCVRNAsubjects (p< 0.001). The same consistent difference in AST mean values of the two groups was also evidenced (0.652 + 0.168 and 0.528 + 0.150 x MNV; p< 0.001). Conclusions: In healthy HCV carriers, infection generally progresses with modest cytolytic activity and therefore, the current MNV are misleading.

We studied serological and tissue markers of Hepatitis B virus (HBV) infection in seven healthy carriers of HBsAg and in 58 patients with chronic active hepatitis (CAH), of whom 20 were HBsAg positive and 38 HBsAg negative. Surface antigen was found as the only marker of HBV infection in the liver tissue of all healthy carriers and HBsAg positive in 40% of the CAH patients. Core antigen was detected only in CAH patients: 7/20 HBsAg positive (in two alone and in five together with HBsAg) and 5/38 HBsAg negative (four with circulating anti-HBs and anti-HBc and one with only anti-HBc). All the healthy carriers of the surface antigen presented HBsAg in the liver as the only marker of HBV. Furthermore, all healthy carriers were found to be anti-HBe positive, whereas in the 16 HBsAg positive CAH patients examined for the e system, HBeAg and anti-HBe were found with the same frequency (43.7%). Of the 33 HBsAg negative CAH patients examined, anti-HBe was present in four who also had circulating anti-HBc and anti-HBs. In HBsAg positive CAH patients core antigen was found in the liver tissue of 4/7 HBeAg positive cases and in 2/7 anti-HBe positive, while surface antigen was detected in 3/7 HBeAg positive, 5/7 anti-HBe positive and in the two HBeAg/anti-HBe negative individuals. In HBsAg negative CAH patients, surface antigen was never found in the liver tissue; core antigen was detected, however, in five who had circulating anti-HBc (one in the presence and four in the absence of anti-HBe). In conclusion, from these data it would appear that the various serological patterns of HBV infection, particularly as concerns the presence of antibodies and presence or absence of HBsAg, are not invariably able to predict whether or not HBV antigens are present in liver tissue or, in other words, if active replication does occur.

The morphologic characterization of portal and lobular infiltrates of chronic active hepatitis (CAH) was performed on liver biopsy sections from 18 patients: 6 HBsAg-positive/anti-delta-negative with tissue signs of hepatitis B virus (HBV) replication, 6 HBsAg-positive/anti-delta-positive with tissue signs of hepatitis delta virus (HDV) replication, and 6 HBsAg-negative without clinical or serologic evidence of autoimmune disease. No statistically significant differences were found among all the three groups of patients studied. Results from the 6 HBsAg-negative cases with T4/T8 ratio greater than 1 confirm the differences reported between this type and autoimmune forms of CAH. The lack of statistically significant differences among patients with CAH of different etiology suggests that etiologic factors play a minor role in determining the characteristics of the inflammatory liver infiltrates.

α1fetoproteina (AFP) e stata da vari AA. riscontrata con notevole frequenza nel siero di soggetti con carcinoma primitivo del fegato, solo sporadicamente in altre epatopatie acute o croniche, specie dell’infanzia, ed in tumori metastatici epatici. Vari AA. hanno inoltre recentemente segnalato frequente associazione tra antigene Australia (Au) e carcinoma epatocellulare. Nel siero di 57 epatopazienti acuti o cronici Au-positivi e di 17 soggetti con neoplasie epatiche primitive o secondarie e stata ricercata AFP mediante elettrosineresi. Con la fissazione del complemento e stata valutata la presenza di Au nel siero dei pazienti con tumore epatico. AFP e stata ritrovata nel 55,5 % dei tumori primitivi del fegato ed in nessuno degli altri casi; Au era presente nel 22,2 % dei casi di carcinoma epatocellulare ed in nessuno dei tumori secondari. Tali dati, unitamente alla frequente associazione di epatoma con cirrosi post-necrotica e con dati anamnestici di pregressa epatite acuta, inducono a prospettare possibili correlazioni patogenetiche tra infezione epatitica ed epatoma. L’esistenza inoltre, sia nella nostra casistica sia in quelle di altri AA., di non trascurabile incidenza di epatopatie croniche e di carcinomi epatocellulari in nuclei familiari, rende suggestiva 1’ipotesi di fattori predisponenti su base genetica, capaci di condizionare le modalite evolutive dell’infezione epatitica.

Only limited data are available on the development of neutralizing antibodies (NAB) in patients with chronic hepatitis C (CHC) treated with pegylated interferon-α (PEG-IFN-α). The aim of this study was to evaluate the immunogenicity of PEG-IFN-α when administered to CHC patients who had or had not previously received standard IFN-α therapy. In addition, the specificities of NAB, together with the ability of leucocyte (LE) -IFN-α to re-establish therapeutic responsiveness in NAB-positive patients, were evaluated. NAB were assessed using a quantitative, standardized, virus-induced cytopathic effect assay. The seroconversion rate to PEG-IFN-α was higher in patients who had received previous standard IFN-α treatment than in those treated exclusively with PEG-IFN-α. Also, NAB produced during PEG-IFN-α therapy were unable to neutralize LE-IFN-α entirely, even though they can neutralize several IFN-α subtypes. In addition, the results indicate that a change to LE-IFN-α therapy can be associated with restoration of clinical responses in NAB-positive patients who had become resistant after showing an initial response to PEG-IFN-α treatment. This study emphasizes the importance of evaluating NAB development in CHC patients who become resistant to PEG-IFN-α treatment, and suggests management alternatives for patients who develop NAB.

The prevalence of serum markers of primary delta infection was determined in 532 patients with acute benign hepatitis B seen in Italy, and in 111 patients with fulminant hepatitis B seen in Italy, France and England. Patients with fulminant hepatitis had significantly higher prevalence of delta markers (43/111, 39%) than did those with benign hepatitis (101/532, 19%). In 25 of the 43 patients with delta-positive fulminant hepatitis, serum markers indicated a primary hepatitis B infection while in the remaining 18, IgM antibody to hepatitis B core antigen was absent, indicating that hepatitis B preceded superinfection with the delta agent. The increased morbidity of HBsAg hepatitis with delta infection may result from the cumulative simultaneous exposure to hepatitis B virus and delta, or from superinfection of HBsAg carriers with delta.

Serological evidence of infection with the hepatitis B virus associated delta agent (delta) was found in 34 of 270 Italian children with HBsAg-positive liver disease. In different histological forms of chronic HBsAg hepatitis the prevalence of delta infection increased in parallel with the activity of the disease and was maximal in children with cirrhosis. During two to seven years of follow up the hepatitis deteriorated in 38% of the 34 patients with delta infection and ameliorated only in 9%. By contrast the disease usually ran a mild course in the 236 delta-negative carriers of HBsAg, with remission in 55% of these children and deterioration in only 7%. The outcome of chronic hepatitis associated with delta infection was not influenced by treatment with steroids and azathioprine. Chronic delta infection in children is usually accompanied by serious liver disease, that has a tendency to progress and is unresponsive to conventional immunosuppressive treatment.

The prevalence of hepatitis delta virus (HDV) infection was significantly higher among the relatives of 79 carriers of HBsAg with antibody to HDV (index cases) than among relatives of 111 carriers without serological evidence of HDV infection (controls). Antibody to HDV was found in 45 of the 80 (56%) carriers of HBsAg in families of index cases but only in 2 of 59 (3%) carriers in families of controls (P less than 0.0001). During follow-up new HDV infection developed in 31% of 13 susceptible carriers in families of index cases, but only in 1.2% of 162 susceptible carriers in families of controls (P less than 0.001). None of the family members previously unexposed to the hepatitis B virus had HDV markers in serum or developed this infection during the follow-up. Familial clustering shows that HDV is transmitted by personal contacts, presumably through the inapparent permucosal or percutaneous passage of virus during close or intimate contact. The family model indicates that endemic HDV is maintained and spread through the network of carriers in the community, and that HBsAg carriers in contact with HBsAg/HDV carriers are at high risk of contracting HDV.

Antibody to the hepatitis delta virus (anti-delta) was detected in 112 out of 2487 (5%) individuals fortuitously found to have the hepatitis B surface antigen (HBsAg) in the blood. Liver function was impaired in 38% (43 of 112) of the anti-delta-positive carriers but in only 9% (215 of 2375) of the anti-delta-negative subjects (p less than 0.001). Liver biopsy specimens were obtained from 31 antibody-positive and 97 antibody-negative subjects with impaired liver function. Important histological changes were observed in 61% of the 31 antibody-positive carriers (7 chronic active hepatitis, 4 active cirrhosis, 8 inactive cirrhosis) but in only 19% of the 97 antibody-negative carriers (p less than 0.001). The presence of anti-delta in serum identifies a subpopulation of apparently healthy HBsAg carriers whose risk of underlying liver disease is four times higher than that in the ordinary carrier. The identification of anti-delta in a symptom-free HBsAg carrier with abnormal liver function is thus an indication for a diagnostic liver biopsy.

A group of 164 consecutive patients with chronic liver disease and 60 healthy HBsAg carriers were investigated in an area highly endemic for hepatitis B virus (HBV). Eighty-two of the 164 patients (50%) were found to be HBsAg-positive and only 39 (24%) had no HBV markers. A statistically significant correlation was found in the HBsAg-positive patients between the HBe system, their age and the time which had elapsed since their acute episode. Thus, the prevalence of HBeAg decreased with increasing age and with increasing time since their acute episodes. Furthermore, a statistically significant correlation was found between the presence of HBeAg and active chronic liver disease. Of the patients with chronic active hepatitis with or without cirrhosis, all patients below the age of 13 years were HBsAg-positive and 72% were also HBeAg-positive. The data suggest that the HBeAg-positivity in HBsAg carriers is of limited duration and that the seroconversion from HBeAg to anti-HBe is related to a histologically less active or inactive stage of the disease.

HBsAg, HBeAg, anti-HBc, anti-HBs, IgM anti-HAV, total and IgM anti-delta (RIA) and IgM anti-HBc (ELISA) have been determined on sera of 72 male patients with acute hepatitis (68 HBsAg positive and 4 anti-HBc-positive) at the onset of the disease and at 2, 4 and 6 months thereafter, and of 77 patients with HBsAg-positive chronic active hepatitis. The results indicate that testing for IgM anti-HBc in acute hepatitis is necessary to identify cases of hepatitis B even in the absence of positivity for HBsAg and/or HBeAg. HBsAg-positive cases, negative for IgM anti-HBc, were due to delta superinfection of chronic carriers of HBsAg. Recovery was always associated with negativity of IgM anti-HBc; IgM anti-HBc persistence was not found in all cases evolved to chronicity. In chronic hepatitis cases positivity for IgM anti-HBc was found only in 39% of the anti-delta-negative and only in 5.5% of the anti-delta-positive cases.

We study the relations between two-dimensional Yang-Mills theory on the torus, topological string theory on a Calabi-Yau threefold whose local geometry is the sum of two line bundles over the torus, and Chern-Simons theory on torus bundles. The chiral partition function of the Yang-Mills gauge theory in the large N limit is shown to coincide with the topological string amplitude computed by topological vertex techniques. We use Yang-Mills theory as an efficient tool for the computation of Gromov-Witten invariants and derive explicitly their relation with Hurwitz numbers of the torus. We calculate the Gopakumar-Vafa invariants, whose integrality gives a non-trivial confirmation of the conjectured nonperturbative relation between two-dimensional Yang-Mills theory and topological string theory. We also demonstrate how the gauge theory leads to a simple combinatorial solution for the Donaldson-Thomas theory of the Calabi-Yau background. We match the instanton representation of Yang-Mills theory on the torus with the nonabelian localization of Chern-Simons gauge theory on torus bundles over the circle. We also comment on how these results can be applied to the computation of exact degeneracies of BPS black holes in the local Calabi-Yau background., Comment: 62 pages, 5 figures

The agri-food sector and supply chain is a foundational component of society and is required for healthy populations across the globe. Feeding the world, not only with enough calories, but with nutritious food that has been sustainably sourced and processed, is a continuous and developing challenge. Despite this, careers in research and development opportunities in the agri-food sector have less visibility in comparison to other sectors, and we argue that agri-food remains under-represented in education and training, from school through to higher education. In this perspective, we explore how diversity in people, skills and education contributes to the agri-food sector, and how fostering this diversity could help to solve some of the big challenges faced in 2021 and beyond. Specific focus is given to education and training schemes, and the lack of agri-food topics in relevant science degrees.(c) 2021 Society of Chemical Industry (SCI).

The aim of our research was to evaluate the effect of different types of vegetable oils, namely extra virgin olive oil (EVOO), olive oil, and sunflower oil, on the chemical properties and volatile profile of traditional Neapolitan pizza, produced by using tomato sauce and EVOO. The quality indices and polyphenols in vegetable oils were analyzed to assess the lipid oxidation as affected by cooking in traditional wood-fired ovens. Peroxide value significantly increased in all vegetable oils, particularly in sunflower oil. EVOO polyphenols decreased about 30% their initial level, particularly simple phenolics. Total individual phenolic compounds decreased from 254.6 to 172.0 mg/kg. Pizza cooking caused the development of some neo-formation volatile compounds caused by lipid oxidation and Maillard reaction. Some positive key odor compounds were found in pizza cooked with EVOO, and the addition of tomato sauce and EVOO caused a dramatic change in its volatile pattern.

Background. Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. Aim. To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. Patients and methods. This retrospective, cross-sectional study involved 1195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. Results. Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. Conclusions. This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. © 2018 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved.

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.