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tBackground: Anaemia (AN) is frequently associated with inflammatory bowel diseases (IBD) and cannegatively influence the quality of life of patients.Aim: To evaluate the prevalence and causes of AN in IBD.Methods: We prospectively performed a one-year multicentre observational study including all IBD casesattending six Units. We also investigated patients’ main serological parameters.Results: The study population included 965 IBD patients (582 CD; 383 UC), of whom 142 were in-patientsand 823 out-patients. AN was diagnosed in 134 out of 965 IBD patients (14%). No significant difference inAN prevalence was observed between CD and UC. The prevalence of AN was higher in the hospitalized IBD(26% in- vs. 11.7% out-patients; p < 0.01; OR 2.2) and in active disease (CD: 34% active vs. 16% inactive;p < 0.01; OR 2.1 – UC: 26% active vs. 19% inactive; p = 0.03; OR 1.3). Iron deficiency was present in 72patients (53.7%), AN of chronic diseases in 12 (8.2%), mixed type AN in 11 (8.2%), thalassemia in 9 (6.7%),and macrocytic AN in 8 (5.9%).Conclusions: In Southern Italy, AN is common in IBD and is more frequent in active disease and hospitalizedpatients. Iron deficiency still remains the major cause of AN in IBD.

OBJECTIVE: The present study aimed to develop a food for special medical purposes (FSMP) and to assess its efficacy as adjuvant therapy in patients with chronic hepatitis C virus (HCV). DESIGN: Open randomized clinical trials with a tomato-based FSMP used as adjuvant treatment to the pharmacological therapy with pegilated interferon and ribavirin. SUBJECTS: Eight healthy volunteers and 39 HCV patients. INTERVENTIONS: For the bioavailability study, healthy subjects consumed 100 g/die FSMP for a week and their serum carotenoid profile at baseline, after the week of administration and 7 days later was determined. The same quantity of FSMP for 6 months by 20 of the 39 HCV patients was consumed in the clinical trial. Serum transaminase, haemoglobin (Hb) and hydroperoxide concentrations during the therapy were monitored in all patients. RESULTS: FSMP consumption caused a fourfold increase of lycopene serum concentration in healthy subjects. A significant increase of carotenoids after 1 month of consumption also in patients with HCV was recorded. Transaminase and Hb serum levels, as well as therapeutic response, were not influenced by FSMP. The decrease in serum hydroperoxides was independent from FSMP consumption in long-term responder patients, whereas nonresponder (NR) patients of FSMP group showed higher reductions than NR patients of Control group. CONCLUSIONS: The FSMP was effective in improving carotenoid status in healthy subjects. In HCV patients, it did not influence the therapeutic response, but it prevented carotenoid serum depletion and it was effective in improving the oxidative status during antiviral therapy in NR patients

Background HBV and HCV reactivation have been widely reported in patients undergoing immunosuppressive therapy (IT); however, few data are available on the risk of reactivation in patients with psoriasis receiving IT. The aim of our study was to assess the prevalence of HBV and HCV infection in patients with psoriasis and to evaluate the effects of IT during the course of the infection. Methods The study included psoriatic patients who attended an Italian tertiary referral hospital from 2009 to 2012. A total of 224 patients were enrolled. We evaluated: HBV and HCV markers, type of IT and the occurrence of viral reactivation. The observational period ranged from the beginning of IT to the last visit, with a mean follow-up period of 54 months. Results Two hundred and twenty patients (135 males and 89 females; mean age 59 years; range 18–86 years) with psoriasis, with or without psoriatic arthritis, receiving conventional IT and/or biological drugs were tested for markers of infection. We identified 23/224 patients (10.2%) with isolated positivity for HBcAb positivity, 36/224 (16%) with positivity for HBsAb/HBcAb, and 15/224 (6.6%) with positivity for HCV-Ab. No patient was HBsAg positive, none of them underwent pre-emptive therapy with lamivudine or other antiviral drugs and no one showed episodes of viral reactivation. Conclusions The prevalence of HBsAg in patients with psoriasis is lower than that observed in the general population. The prevalence of isolated positivity for HBcAb and of combined positivity for HBcAb and HBsAb is 10.2% and 16%, respectively. The prevalence of HCV infection (HCV-RNA+) is 4%. In patients with psoriasis and HCV-Ab or HBcAb positivity, the IT seems to be safe, regardless of the type of drugs.

Some reports have demonstrated an inadequate response to hepatitis B vaccination in patients affected by celiac disease. The aim of our study was to evaluate hepatitis B vaccination response in relation to gluten exposure status in patients with celiac disease. To measure the gluten exposure status at the time of vaccination, we considered three groups: group A (exposed to gluten), including patients vaccinated as 12-year-old adolescents (the celiac disease diagnosis was established after vaccination); group B (not exposed to gluten), including patients vaccinated as 12-year-old adolescents on a gluten-free diet at the time of vaccination; and group C (infants), including patients vaccinated at birth. The response of celiac patients to hepatitis B vaccination was compared to that of healthy subjects, i.e., those in the control group (group D). This study included 163 celiac patients (group A, 57 patients; group B, 46 patients; and group C, 60 patients) and 48 controls (group D). An inadequate response to hepatitis B immunization was present in 43.9% of patients in group A, 34.8% of patients in group B, 58.3% of patients in group C, and 8.3% of patients in group D (group A versus group D,P< 0.001; group B versus group D,P= 0.002; group C versus group D,P= 0.001) (no significant difference for group A versus group B and group A versus group C was evident). Our data suggest that gluten exposure does not influence the response to hepatitis B immunization and that the human leukocyte antigen probably plays the main immunological role in poor responses to hepatitis B-vaccinated celiac patients.

Chronic liver damage is a widespread pathology characterized by a progressive evolution from steatosis to chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. As the oxidative stress plays a central role in liver diseases pathogenesis and progression, the use of antioxidants have been proposed as therapeutic agents, as well as drug coadjuvants, to counteract liver damage. In this work in vitro and in vivo studies, with emphasis on humans and animals experiments, have been considered and reviewed according to antioxidant typologies. Great differences emerge as far as ingested doses, bioavailability and liver ability to accumulate the various compounds. Results available up to now suggest that lycopene-rich foods could be proposed in therapeutic treatment of some liver pathologies. On the other hand contradictory results have been obtained with alpha-tocopherol, beta-carotene and trans-resveratrol. Quercetin, silymarin, esculetin and thyme and rosemary among phenolic compounds need further studies.

Summary objectiveThe aim of this study was to investigate changes in thyroid hormone metabolism in relation to the development of hepatocellular carcinoma (HCC) in patients with HCV-related liver cirrhosis. materials and methods The study group (Group A) comprised 31 patients (25 M, 6 F; median age 62·1 years, range 54·0–81·5 years) affected by HCV-related liver cirrhosis with superimposed HCC. Acute and chronic systemic disease, other than cirrhosis, inducing ‘euthyroid sick syndrome’ was excluded in all patients. Serum TSH, FT4, FT3, rT3, and thyroxine-binding globulin (TBG) levels were retrospectively evaluated in frozen aliquots drawn at the time of tumour diagnosis and every 6 months for 3–7 years before HCC diagnosis. The control group (Group B) comprised 29 patients affected by HCV-related liver cirrhosis without HCC, matched for sex, age and grade of liver dysfunction. results At the time of HCC diagnosis, all patients in Group A were euthyroid with serum TSH, FT4, FT3 and TBG values not significantly different from those of cirrhotic patients of Group B. However, at diagnosis Group A patients had serum rT3 values that were significantly higher than those in Group B (35·0 ng/dl, range 12·0–162·0 vs. 19·0 ng/dl, range 10·0–51·0; Group A vs. Group B; P

Summary Background : The consumption of unfiltered coffee, containing bioactive diterpenes, causes an increase in plasma homocysteine concentration. A slight increase in plasma homocysteine is also caused by large quantities of filtered coffee. Coffee terpenes also raise plasma glutathione in mice. Aim : To verify the effect of Italian-style coffee consumption on the plasma concentration of glutathione and homocysteine in healthy subjects. Methods : Twenty-two volunteers consumed five cups of coffee per day for 1 week and maintained their usual diet. Five subjects were enrolled as controls. The intervention trial was preceded and followed by seven coffee-free days. Results : Plasma glutathione increased by 16% (P

Background: Alpha interferon (IFN) alone or in combination with Ribavirin (RBV) is the treatment of choice for HCV related chronic liver disease. There are many types of alpha IFN and to date only few reports are available comparing different types of alpha interferon. We run a randomised controlled trial with the aim to compare tolerability and efficacy of two different types of IFN: recombinant alpha 2b interferon (IFN-R) and leukocyte alpha n-3 interferon (IFN-L) at the same dosage of 3 MU subcutaneously thrice weekly for one year. Methods: one hundred sixty eight consecutive anti-HCV positive naive patients, 34 mild chronic active hepatitis (MCH), 81 moderate-severe hepatitis (MSCR) and 53 active cirrhosis (CIRR) that met the inclusion criteria were enrolled into the study. The diagnosis of HCV chronic liver disease was established by liver biopsy performed on patients with abnormal serum alanine aminotransferase (ALT) value for at least one year. HCV serology: all patients were tested for confirmatory test RIBA II, HCV-RNA, and identification of viral genotype. Patients were randomised to receive either IFN-R or IFN-L. Follow-up continued for at least two years after stopping treatment. Results: no significant differences were observed between the two groups of treatment as far as the incidence of side effects is concerned. Tolerability was good: only 11 in IFN-R and 8 patients IFN-L group respectively had to stop therapy due to side effects. The two types of IFN showed a comparable efficacy: an end of therapy response was observed in 34% of IFN-R and 30% of IFN-L patients; a sustained response was seen in 16% of IFN-R and in 19% of IFN-L patients. Conclusion: in the treatment of patients with chronic hepatitis C there was no statistically significant difference in tolerability and efficacy between the two IFNs tested.

We would like to share with the readers the results of our experience in 50 celiac disease (CD) patients, enrolled between September 2012 and April 2013, who were referred to our third-level CD Unit. The fecal calprotectin (FC) concentration of 50 adults with newly diagnosed CD was compared to that of a control group of 50 healthy subjects. FC level was determined by enzyme linked immunosorbent assay with diagnostic cut-off of 75 μg/g. In addition, we tried to correlate the FC level with symptoms, histological severity of CD (Marsh grade) and level of tissue transglutaminase antibodies (aTg) in CD patients. Finally, FC level was increased in five CD patients and in four controls (10% vs 8%, P = NS); mean FC concentration of patients and controls were 57.7 (SD ± 29.1) and 45.1 (SD ± 38.4) respectively. Furthermore, no significant correlation was seen between FC levels and symptoms/Marsh grade/aTg. The five CD patients did not show inflammatory lesions (e.g., ulcers, erosions) at upper endoscopy. The four healthy controls with positive FC were followed-up for further six months; in this observational period they did not show clinical signs of any underlying disease. On these bases, we think that FC is not able to investigate the subclinical inflammatory changes of active CD and FC should be considered a useless tool in the diagnostic work-up of uncomplicated CD but it should be accompanied by aTg when ruling out organic disease in patients with irritable bowel syndrome.

Coffee consumption is inversely related to the degree of liver injury in patients with nonalcoholic fatty liver disease (NAFLD). Molecular mediators contributing to coffee's beneficial effects in NAFLD remain to be elucidated. In this study, we administrated decaffeinated espresso coffee or vehicle to rats fed an high-fat diet (HFD) for 12 weeks and examined the effects of coffee on liver injury by using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) proteomic analysis combined with mass spectrometry. Rats fed an HFD and water developed panacinar steatosis, lobular inflammation, and mild fibrosis, whereas rats fed an HFD and coffee exhibited only mild steatosis. Coffee consumption increased liver expression of the endoplasmic reticulum chaperones glucose-related protein 78 and protein disulfide-isomerase A3; similarly, coffee drinking enhanced the expression of the mitochondrial chaperones heat stress protein 70 and DJ-1. Furthermore, in agreement with reduced hepatic levels of 8-isoprostanes and 8-hydroxy-2′-deoxyguanosine, proteomic analysis showed that coffee consumption induces the expression of master regulators of redox status (i.e., peroxiredoxin 1, glutathione S-transferase α2, and D-dopachrome tautomerase). Last, proteomics revealed an association of coffee intake with decreased expression of electron transfer flavoprotein subunit α, a component of the mitochondrial respiratory chain, involved in de novo lipogenesis. In this study, we were able to identify by proteomic analysis the stress proteins mediating the antioxidant effects of coffee; moreover, we establish for the first time the contribution of specific coffee-induced endoplasmic reticulum and mitochondrial chaperones ensuring correct protein folding and degradation in the liver.

SummaryBackground The new ESPGHAN guidelines for diagnosis of paediatric coeliac disease suggest to avoid biopsy in genetically pre-disposed and symptomatic individuals with positive anti-endomysial antibodies (EMA) and anti-tissue transglutaminases (a-tTG). However, duodenal biopsy remains the gold standard in adult coeliac disease. Aims To establish the cut-off values of a-tTG, which would: predict the presence of duodenal histology (Marsh ≥2) diagnostic for coeliac disease; and predict the presence of villous atrophy (Marsh 3) in adults. Methods We performed an observational prospective study including all consecutive adult patients with suspected coeliac disease. All subjects were tested for EMA and a-tTG. Coeliac disease diagnosis was made in presence of Marsh ≥2, a-tTG >7 U/mL and positive EMA. A ROC curve was constructed to establish the best specificity cut-off of a-tTG levels, which would predict the presence of Marsh ≥2 and Marsh 3 at histology. Results The study included 310 patients with positive antibodies. Histology showed Marsh 1 in 8.7%, Marsh 2 in 3.5%, Marsh 3 in 87.7%. The best cut-off value of a-tTG for predicting Marsh ≥2 was 45 U/mL (sensitivity 70%; specificity 100%; PPV 100%; NPV 24.1%); the best cut-off for predicting villous atrophy was 62.4 U/mL (sensitivity 69%, specificity 100%; PPV 100%; NPV 31%). Conclusions The diagnosis of coeliac disease can be reached without histology in adult patients with positive EMA and a-tTG levels >45 U/mL. An a-tTG level >62.4 was diagnostic for villous atrophy. These results could contribute to improving the diagnosis of coeliac disease by allowing for a significant reduction in diagnosis-related costs.

In 2014, the European Medicines Agency (EMA) has given the license to two new direct-acting antiviral: sofosbuvir and simeprevir. The evidence provided by the studies, reported a high rate of SVR even in patients with decompensated cirrhosis. This and other innovative elements are potentially adept at changing the entire natural course of HCV. However, the dramatic prevalence rates of HCV observed in Italy, and the high prices that are expected to be required by the pharmaceutical industry, raises some critical issues about how to regulate access to such drugs. The objective of this article is to present a new decision model for the evaluation of novel therapies for HCV. This model is intended to provide a tool for the decision-maker that seeks to address the main issues related to the introduction of HCV new treatments. The model that we have structured follows the classic Bayesian approach, using data from reference literature for staging the action of treatments depending on the level of fibrosis (F0, F1, F2, F3, F4). The model is designed to consider patients with all genotypes and allows to make comparisons between innovative and traditional therapies (dual, triple, IFN free, PI combinations, etc.), for both experienced and naïve patients. In addition, the model is used to simulate mixed cohorts of patients, representing a population with HCV with different levels of fibrosis and different genotypes. To show the potential of the model, we created some simple scenarios assuming different levels of SVR and pricing. The results of our model show that, even assuming an SVR rate of 100%, the administration of new treatments for HCV subjects F1 / 2 has an incremental cost-effectiveness ratio not sustainable. In contrast, for the subjects F3 and F4, low incremental SVR rates and an incremental cost of the innovative therapy of € 40,000 would be cost effective. The added value of this model is its versatility and applicability to diverse assessment needs. In addition, the model offers an opportunity for reflection even to the industry, which in the years to come will have to develop strategies for entering the market and offer sustainable prices for decision-makers and at the same time remunerate the investment in research and development consistently with the expectations of the shareholders.

Background & Aims Multipotent stem/progenitor cells are found in peribiliary glands throughout human biliary trees and are able to generate mature cells of hepato-biliary and pancreatic endocrine lineages. The presence of endodermal stem/progenitors in human gallbladder was explored. Methods Gallbladders were obtained from organ donors and laparoscopic surgery for symptomatic cholelithiasis. Tissues or isolated cells were characterized by immunohistochemistry and flow cytometry. EpCAM+ (Epithelial Cell Adhesion Molecule) cells were immunoselected by magnetic microbeads, plated onto plastic in self-replication conditions and subsequently transferred to distinct serum-free, hormonally defined media tailored for differentiation to specific adult fates. In vivo studies were conducted in an experimental model of liver cirrhosis. Results The gallbladder does not have peribiliary glands, but it has stem/progenitors organized instead in mucosal crypts. Most of these can be isolated by immune-selection for EpCAM. Approximately 10% of EpCAM+ cells in situ and of immunoselected EpCAM+ cells co-expressed multiple pluripotency genes and various stem cell markers; other EpCAM+ cells qualified as progenitors. Single EpCAM+ cells demonstrated clonogenic expansion ex vivo with maintenance of stemness in self-replication conditions. Freshly isolated or cultured EpCAM+ cells could be differentiated to multiple, distinct adult fates: cords of albumin-secreting hepatocytes, branching ducts of secretin receptor+ cholangiocytes, or glucose-responsive, insulin/glucagon-secreting neoislets. EpCAM+ cells transplanted in vivo in immune-compromised hosts gave rise to human albumin-producing hepatocytes and to human Cytokeratin7+ cholangiocytes occurring in higher numbers when transplanted in cirrhotic mice. Conclusions Human gallbladders contain easily isolatable cells with phenotypic and biological properties of multipotent, endodermal stem cells.

Background. A high incidence of thyroid autoantibodies and/or disorders was observed in subjects with hepatitis C virus-related chronic hepatitis during interferon-alpha therapy. Aim. To evaluate whether thyroid autoimmunity and dysfunction, induced by interferon-alpha therapy, could be viewed as predictors for treatment response and as valid prognostic markers of liver disease progression. Patients. A total of 136 subjects (96 males/40 females; median age 48 years; range 23–64) affected by biopsy-proven chronic hepatitis C (33.1 % with compensated liver cirrhosis). Methods. All subjects were treated with interferon-alpha therapy at 6 MU 3 times weekly for 12 months and then followed up for an average period of 60 months (range 12–108). Routine laboratory tests, virological assessment, liver ultrasound, thyroid function tests (serum free-triiodothyronine, free-thyroxine, serum thyrotropin), and autoimmunity were performed for all subjects. Results. Percentage of thyroid autoimmunity and thyroid dysfunction in long-term responders was not significantly different compared to that in non-responders (47.0% and 11.8% vs 35.3% and 5.9%, respectively; non significant). The multivariate model demonstrated that the absence of cirrhosis was the only factor significantly related to successful response to therapy (odds ratio: 14.9; 95% confidence interval: 1.9–115.0 for chronic hepatitis C vs presence of cirrhosis). Moreover, the occurrence of thyroid autoimmunity during interferon therapy was similar both in patients with or without worsening of liver disease (33.3% and 39.8%, respectively, p = not significant). No subject with ongoing liver disease developed thyroid dysfunction during treatment, as opposed to the 10 118 (8.4%) with a better course of liver disease; however, this difference was not statistically significant. The multivariate model showed that age was the only covariate significantly associated with unfavourable outcome of liver disease (odds ratio: 18.6; 95% confidence interval: 2.3–151.9, for those over 48 years vs younger patients). Conclusions. There is no evidence that the immune mechanism involved in the pathogenesis of thyroid autoimmune phenomena is the same as that regulating the therapeutic clearance of HCV or modulating the unfavourable course of HCV-related chronic hepatitis. However, our study confirmed that liver disease seems to progress more slowly in younger subjects.

Background. Quite often subjects affected by chronic hepatitis C virus infection have no clinical signs of liver disease and serum aminotransferase values never go beyond the upper limit of normal. Yet these subjects, defined “asymptomatic HCV carriers”, often have active viral replication and various degrees of histological damage. Aims. To verify, in a population of antibody to hepatitis C virus carriers, if normal serum aminotransferase values in hepatitis C virus-RNA positive differed considerably from those in hepatitis C virus-RNA negative subjects. Subjects/Methods. We followed 24 anti-hepatitis C virus-positive subjects (15 hepatitis C virus-RNA positive and 9 negative) by measuring alanine and aspartate aminotransferase levels at 3-month intervals for a median of 40 months (range 6–77). Results. Determinations resulted repeatedly and rigorously within the normal range in all participants. Alanine aminotransferase values were higher in hepatitis C virus-RNA positives than in negatives (mean ± SD: 0.609±0.172 vs 0.434±0.153 times the upper limit of normal; p

the AFP, the poorer the prognosis, but no good evidence in the literature exists on the minority of patients with HCC who do not secrete AFP. Our aim was to analyse this sub-group of patients from a cohort with advanced HCC treated with Sorafenib, and assess survival outcomes. Methods: Consecutive patients with a confirmed diagnosis of HCC as per AASLD criteria, treated with Sorafenib at Queen Elizabeth Hospital Birmingham UK, between April 2009 and March 2014 were included in the analysis. We took our local reference range of 400ng/ml (HR: 1.02, p = 0.89). The Kaplan–Meier curve presented shows the separation of survival curves for the 3 groups. Conclusions: There is very little published in the literature about the AFP non-secretor HCC sub-group. Our data shows that this sub-group has better prognosis compared to patients with AFP secretory HCC. We believe that this data is important for clinicians and patients for prognostication and decision making. P0340 CLINICAL PATTERNS OF HEPATOCELLULAR CARCINOMA (HCC) IN NON ALCOHOLIC FATTY LIVER DISEASE (NAFLD): A MULTICENTER CASE–CONTROL STUDY F. Piscaglia, G. Svegliati Baroni, A. Barchetti, A. Pecorelli, S. Marinelli, C. Tiribelli, S. Bellentani, HCC-NAFLD Italian Study (full list exceeds available space) Bolondi L, Zoli M, Trevisani F, Malagotti D, Bugianesi E, Vanni E, Mezzabotta L, Cabibbo G, Petta S, Fracanzani A, Fargion S, Marra F, Fani B, Sacco R, Morisco F, Caporaso F, Guarino M, et al.. Dpt of Medical and Surgical Sciences, University of Bologna, Uni of Internal Medicine, University of Bologna, Bologna, Gastroenterology, University of Ancona, Ancona, Liver Research Center, Science Park – Basovizza Campus, Trieste, Italy E-mail: fabio.piscaglia@unibo.it

Background/Aim: The aim of this study was to evaluate if plasma levels of alpha-glutathione-S-transferases (determined in basal conditions and monthly for 1 year during and 1 year after interferon therapy) could characterize patients who show only a primary response. Methods: We studied 48 patients with biopsy-proven, hepatitis C virus ribonucleic acid positive chronic hepatitis treated with interferon: 18 were "Sustained Responders", 12 "Relapsers" and 18 "Non-Responders". Results: Relapsers showed higher basal levels of alpha-glutathione-S-transferases, which remained higher than normal even when alanine aminotransferases normalized. No correlation was documented between alpha-glutathione-S-transferase levels and all other parameters examined (alanine aminotransferases, γ-glutamyl-transpeptidase, viremia, and histological activity index). Conclusions: These findings suggest that alpha-glutathione-S-transferase levels may be considered a predictive index of response to interferon therapy in chronic hepatitis C patients.

Fresh and dried figs are important components of the Mediterranean diet. In Cilento (Southern Italy), figs belonging to cultivar "Dottato" are used for the production of "PDO Cilento white figs," as dried figs. In this article, we reported the characterization of the phenolic compounds in 19 fig samples: 9 fresh figs cultivar "Dottato" from Cilento (Italy), 10 dried fig samples from Cilento (2), Turkey (6), and Greece (2). The following phenolic compounds were identified and quantified by high-performance liquid chromatography (HPLC)/UV-DAD: chlorogenic acid, protocatechuic acid, vanillic acid, luteolin-3,7-di-O-glucoside, luteolin 7-glucoside, apigenin-7-O-rutinoside, rutin, quercetin-3-glucoside, and cyanidin-3-O-rutinoside. A discriminative analysis between the peel and pulp of the samples was carried out. The 1st crop ("breba") and the 2nd one (full crop) from Dottato figs were considered, as well as the effect of fig pollination. The majority of the phenolic compounds were predominant in the fig peel. Significant quantitative differences were found among fresh figs, whereas also some qualitative differences were obtained between fresh and dried figs from the same origin in Dottato cultivar, and among dried figs from different origins. Breba crop resulted richer in phenolics than figs of the 2nd crop. Considering the dried figs, the Turkish ones had the highest concentration in phenolic compounds. Other compounds such as the aminoacids tyrosine and tryptophan were also detected by HPLC-DAD analysis in Dottato figs, probably due to the similarity of their chemical structure.The results of this research could be useful to deepen the knowledge about the phenolic composition of a fruit that is particularly appreciated in Mediterranean area and presents an increasing interest worldwide. We also characterized a typical Italian fig (Cilento Dottato) that has relevant economical importance in Southern Italy; thus, our work could be applied by producers and industries for the valorization of dried figs as high-quality products. From the consumer viewpoint, a comparison among dried figs from different origins found on the retail market has a huge significance to inform about what the market offers and what product is the richest one in polyphenol content.

In recent years, a number of case reports and clinical studies have highlighted the risk of hepatitis B and C virus reactivation in patients with inflammatory bowel disease who are treated with immunosuppressive drugs. The cases of viral hepatitis reactivation that have been reported are characterized by a wide range of clinical manifestations, from viremia without clinically relevant manifestations to fulminant life-threatening hepatitis. The development and dissemination of biological immunosuppressive drugs have led to a significant increase in the number of reports of interest to physicians in a variety of clinical settings. On this topic, there have been a number of published guidelines and reviews that have collected the available evidence, providing recommendations on prophylactic and therapeutic strategies and methods for monitoring patients at risk. However, it should be noted that, to date, very few clinical studies have been published, and most of the recommendations have been borrowed from other clinical settings. The published studies are mostly retrospective and are based on very heterogeneous populations, using different therapeutic and prophylactic regimens and obtaining conflicting results. Thus, it seems clear that it is desirable to concentrate our efforts on prospective studies, not conducting further reviews of the literature in the continued absence of new evidence.

Helicobacter pylori (H. pylori) is a widespread pathogen infecting about 40% of people living in urban areas and over 90% of people living in the developing regions of the world. H. pylori is well-documented as the main factor in the pathogenesis of peptic ulcer disease, chronic gastritis, and gastric malignancies such as cancer and mucosa-associated lymphoid tissue-lymphoma; hence, its eradication is strongly recommended. The Maastricht IV consensus, which focused on the management of H. pylori infection, set important new strategies in terms of treatment approaches, particularly with regards to first- and second-line treatment protocols and led to improved knowledge and understanding of H. pylori resistance to antibiotics. In recent years, various fluoroquinolone-based protocols, mainly including levofloxacin, have been proposed and effectively tested at all therapeutic lines for H. pylori eradication. The aim of the present paper is to review the scientific literature focused on the use of fluoroquinolones in eradicating H. pylori.

BACKGROUND Both thiopurines and anti-tumor necrosis factor (TNF) α agents are effective for treating Crohn's disease (CD) as they can induce clinical remission (CR) and mucosal healing (MH) in most patients. Nevertheless, data on transmural healing (TH) induced by thiopurines and anti-TNF-α agents are still lacking. This study aimed to explore the rate of TH evaluated by bowel sonography in patients with CD treated with biologics and immunosuppressors and its correlation with CR and MH. METHODS We performed an observational longitudinal study evaluating TH, CR, and MH in all patients with CD attending our clinic who would complete 2 years of maintenance treatment with biologics or thiopurines. CR and MH were assessed in accordance with current literature, whereas TH was recorded using bowel sonography. All patients underwent endoscopy and bowel sonography before starting treatment and 2 years later. RESULTS The study included 66 patients with CD treated with biologics and 67 patients receiving thiopurines. Finally, TH was present in 17 patients on biologics and only 3 patients treated with thiopurines (25% versus 4%; P < 0.01; odds ratio = 6.2). CR was achieved in 37 patients on biologics and in 34 patients on thiopurines (59.7% versus 53%; P = not significant), whereas MH was more frequent in patients treated with anti-TNF-α agents even though without statistical significance (38% versus 25%; P = not significant). CONCLUSIONS TH can be achieved in approximately 25% of patients with CD treated with anti-TNF-α agents and significantly correlates with MH. Further studies are needed to define the potential role of TH as long-term prognostic factor.

Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy; however, few data are available about the risk of HBV and HCV reactivation in patients with inflammatory bowel disease, receiving immunosuppressive drugs. The aim of our study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with inflammatory bowel disease and to value the effects of immunosuppressive therapy during the course of the infection. Retrospective observational multicenter study included all consecutive patients with inflammatory bowel disease who have attended seven Italian tertiary referral hospitals in the last decade. A total of 5096 patients were consecutively included: 2485 Crohn's disease and 2611 Ulcerative Colitis. 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV-positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (six HBsAg+; four isolated anti-HBc+ and 10 anti-HCV+). One of six patients showed HBsAg+ and one of four isolated anti-HBc+ experienced reactivation of hepatitis. Two of six HBsAg patients received prophylactic therapy with lamivudine. Only one of 10 anti-HCV+ patients showed mild increase in viral load and ALT elevation. Screening procedures for HBV and HCV infection at diagnosis have been underused in patients with inflammatory bowel disease. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previous reported.

UnlabelledThe aim of the present work was to test the potential of Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) in the diagnosis of liver cirrhosis and the assessment of disease severity by direct analysis of exhaled breath. Twenty-six volunteers have been enrolled in this study: 12 patients (M/F 8/4, mean age 70.5 years, min-max 42-80 years) with liver cirrhosis of different etiologies and at different severity of disease and 14 healthy subjects (M/F 5/9, mean age 52.3 years, min-max 35-77 years). Real time breath analysis was performed on fasting subjects using a buffered end-tidal on-line sampler directly coupled to a PTR-ToF-MS. Twelve volatile organic compounds (VOCs) resulted significantly differently in cirrhotic patients (CP) compared to healthy controls (CTRL): four ketones (2-butanone, 2- or 3- pentanone, C8-ketone, C9-ketone), two terpenes (monoterpene, monoterpene related), four sulphur or nitrogen compounds (sulfoxide-compound, S-compound, NS-compound, N-compound) and two alcohols (heptadienol, methanol). Seven VOCs (2-butanone, C8-ketone, a monoterpene, 2,4-heptadienol and three compounds containing N, S or NS) resulted significantly differently in compensate cirrhotic patients (Child-Pugh A; CP-A) and decompensated cirrhotic subjects (Child-Pugh B+C; CP-B+C). ROC (Receiver Operating Characteristic) analysis was performed considering three contrast groups: CP vs CTRL, CP-A vs CTRL and CP-A vs CP-B+C. In these comparisons monoterpene and N-compound showed the best diagnostic performance.ConclusionsBreath analysis by PTR-ToF-MS was able to distinguish cirrhotic patients from healthy subjects and to discriminate those with well compensated liver disease from those at more advanced severity stage. A breath-print of liver cirrhosis was assessed for the first time.

Background & aims: We previously demonstrated the efficacy of garlic extract (GE) in the prevention of rat liver fibrosis by inhibiting tissue transglutaminase (tTG) activity. In the present study we aimed to evaluate the potential of GE in the regression of liver fibrosis and the underlining mechanism. Methods: Male Wistar rats were i.p. injected, twice a week, for 7 weeks, with CCl4 to develop liver fibrosis. Successively, a group was immediately sacrificed, while the remaining two groups received the GE or the vehicle, respectively, over the following 2 wks. A group of normal rats was also included in the study. Liver function, histology, and collagen deposition in parallel with gene and protein expression of α-SMA, tTG, TGF-β1, SEMA-7A, and metalloproteinase inhibitor 1 (TIMP1) as well as measure of active by total TGF-β1 were assessed. Results: CCl4 administration increased alanine-aminotransferase (ALT) activity, hepatic collagen deposition and gene and protein expression of all monitored markers. GE, but not the sole vehicle, restored liver histology and function by decreasing fibrogenesis markers (α-SMA, tTG, TGF-β1, SEMA-7A and TIMP1). Active by total TGF-β1 was significantly reduced (p < 0.05) in GE treated rats compared to the CCl4 at 7 weeks, and vehicle rats. Conclusions: These findings concurrently suggested that GE elicited therapeutic effect against liver fibrosis. Regression of liver fibrosis occurred by reducing myofibroblasts (through modulation of HSCs activation mechanisms), remodelling extracellular matrix (through increase of its degradation) and regenerating liver tissue and functions: three processes regulated by fine mechanisms where active TGF-β1 and tTG play a central role.

Objective: Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4-induced rat liver fibrosis. Results: CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P < 0.001 in all cases). Circulating levels of proinflammatory cytokine TNF-a were significantly increased in rats with liver fibrosis as compared with normal rats, while symbiotic treatment normalized the plasma levels of TNF-a and significantly enhanced anti-inflammatory cytokine IL 10. TNF-a, TGF-b, TLR4, TLR2, iNOS and a-SMA mRNA expression in the liver were up-regulated in rats with CCl4-induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 + symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Conclusions: Our results provide evidence that in CCl4-induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis.

Background: Recent evidence indicate that gut microbiota plays a key role in the development of NAFLD through the gut-liver axis. An altered gut permeability induced by alterations of tight junction (TJ) proteins allows the passage of bacteria and substances leading to liver inflammation, hepatocyte damage and fibrosis. This study aims to evaluate the influence of decaffeinated coffee on gut permeability in a rat model of fat liver damage induced by a high fat diet (HFD). Methods: Twelve Male Wistar rats were assigned to 3 groups. The first group received HFD for 5 months and drank water; the second group received HFD for 5 months and drank water added with 1.2mL decaffeinated coffee/day starting from the 4th month; the third group received standard diet (SD) and drank water. Protein and mRNA expression levels of Toll-Like Receptor-4 (TLR-4), Occludin and Zonula occludens-1 (ZO-1) were assessed in rat intestines. Results: A significant reduction of Occludin and ZO-1 was observed in HFD fed rats (0.97±0.05 vs 0.15±0.08 p˂0.01, and 0.97±0.05 vs 0.57±0.14 p˂0.001, respectively); this reduction was reverted in HFD+COFFEE rats (0.15±0.08 vs 0.83±0.27 p˂0.01, and 0.57±0.14 vs 0.85±0.12 p˂0.01, respectively). The TLR-4 expression up-regulated by HFD was partially reduced by coffee administration. Conclusions: HFD impairs the intestinal tight junction barrier integrity. Coffee increases the expression of tight junctions proteins reverting the altered gut permeability, and reduces TLR4 expression. Key Words: NAFLD, coffee, Occludin, Zonulin-1, rat model, TLR4.