On the operational definition of fatty liver

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Low Anisakis-specific IgE prevalence in dyspeptic patients in Italy – a retrospective study

Abstract The aims of this case-control study were to determine the prevalence of Anisakis-specific IgE in patients reporting chronic or acute gastrointestinal (GI) symptoms and to investigate the correlation with raw fish ingestion habits. A group of patients undergoing gastric endoscopy and a control group of healty subjects answered a self-administered questionnaire on their food habits, presence of symptoms (both allergic and not allergic), and general life style. The presence of anti-Anisakis IgE has been evaluated using a serum immunoCAP assay. Our data show a low prevalence of IgE directed against Anisakis allergens in Italy in dyspeptic patients, despite the high consumption of poorly cooked fish. These findings does not correlate with the results of studies from other Mediterranean countries, such as Spain, for example.The general prevalence of Anisakis allergens sensitization in Italy could be further investigated through screenings in the allergic population, especially on those patients who claim to have developed a fish allergy and with history of raw fish consumption. Moreover, the attention should be moved on recent allergic reactions associated with fishing ingestion. This could in fact indicate a recent encounter with the parasite. Finally, we must underline that the evaluation of Anisakis-specific IgG would have probably shown a difference in terms of exposure between the two groups; thus, it might be useful to detect also this antibody class in future population-based studies

Thermal Care of Functional Dyspepsia Based on Bicarbonate-Sulphate-Calcium Water: A Sequential Clinical Trial

Drug treatment of functional dyspepsia is often unsatisfactory. We assessed the efficacy of a bicarbonate-sulphate-calcium thermal water cycle of 12 days, in patients with functional dyspepsia. Patients with functional dyspepsia were sent by their general practitioners to 12 days of treatment with thermal water, 200–400 ml in the morning, at temperature of 33°C (91.4 F) and were evaluated on a strict intention to treat basis. Four efficacy endpoints were analyzed as follows: (i) reduction of the global symptoms score, (ii) reduction of intensity to a level not interfering with everyday activities, (iii) specific efficacy on ulcer-like or dysmotility-like dyspepsia and (iv) esophageal or abdominal-associated symptoms. Statistical significance was reached for all three primary outcomes after the first 29 consecutive patients. Thermal water reduced the global symptom score, reduced intensity of symptoms to a level not interfering with everyday activity, but was unable to completely suppress all symptoms. A parallel effect emerged for ulcer-like and dyspepsia-like subgroups. The effect on heartburn and abdominal symptoms was not significant, suggesting a specific effect of the water on the gastric and duodenal wall. The Roma II criteria identify a natural kind of dyspepsia that improves with thermal water. Ulcer-like and dysmotility-like are not therapeutically distinguishable subgroups. Patients with dominant esophageal or abdominal symptoms should receive a different therapy. Sequential methods are very effective for the evaluation of traditional care practices and should be considered preliminary and integrative to randomized controlled trials in this context

Inhibition of Natural Killer Cells through Engagement of CD81 by the Major Hepatitis C Virus Envelope Protein

The immune response against hepatitis C virus (HCV) is rarely effective at clearing the virus, resulting in ∼170 million chronic HCV infections worldwide. Here we report that ligation of an HCV receptor (CD81) inhibits natural killer (NK) cells. Cross-linking of CD81 by the major envelope protein of HCV (HCV-E2) or anti-CD81 antibodies blocks NK cell activation, cytokine production, cytotoxic granule release, and proliferation. This inhibitory effect was observed using both activated and resting NK cells. Conversely, on NK-like T cell clones, including those expressing NK cell inhibitory receptors, CD81 ligation delivered a costimulatory signal. Engagement of CD81 on NK cells blocks tyrosine phosphorylation through a mechanism which is distinct from the negative signaling pathways associated with NK cell inhibitory receptors for major histocompatibility complex class I. These results implicate HCV-E2–mediated inhibition of NK cells as an efficient HCV evasion strategy targeting the early antiviral activities of NK cells and allowing the virus to establish itself as a chronic infection

Circulating Hepatitis B Surface Antigen Particles Carry Hepatocellular microRNAs

Hepatitis B virus (HBV) produces high quantities of subviral surface antigen particles (HBsAg) which circulate in the blood outnumbering virions of about 1\103–6 times. In individuals coinfected with the defective hepatitis Delta virus (HDV) the small HDV-RNA-genome and Delta antigen circulate as ribonucleoprotein complexes within HBsAg subviral particles. We addressed the question whether subviral HBsAg particles may carry in the same way cellular microRNAs (miRNAs) which are released into the bloodstream within different subcellular forms such as exosomes and microvescicles. Circulating HBsAg particles were isolated from sera of 11 HBsAg carriers by selective immunoprecipitation with monoclonal anti-HBs-IgG, total RNA was extracted and human miRNAs were screened by TaqMan real-time quantitative PCR Arrays. Thirty-nine human miRNAs were found to be significantly associated with the immunoprecipitated HBsAg, as determined by both comparative DDCT analysis and non-parametric tests (Mann-Whitney, p<0.05) with respect to controls. Moreover immunoprecipitated HBsAg particles contained Ago2 protein that could be revealed in ELISA only after 0.5% NP40. HBsAg associated miRNAs were liver-specific (most frequent = miR-27a, miR-30b, miR-122, miR-126 and miR-145) as well as immune regulatory (most frequent = miR-106b and miR-223). Computationally predicted target genes of HBsAg-associated miRNAs highlighted molecular pathways dealing with host-pathoge

Liver and White/Brown Fat Dystrophy Associates with Gut Microbiota and Metabolomic Alterations in 3xTg Alzheimer's Disease Mouse Model

Metabolic impairments and liver and adipose depots alterations were reported in subjects with Alzheimer's disease (AD), highlighting the role of the liver-adipose-tissue-brain axis in AD pathophysiology. The gut microbiota might play a modulating role. We investigated the alterations to the liver and white/brown adipose tissues (W/BAT) and their relationships with serum and gut metabolites and gut bacteria in a 3xTg mouse model during AD onset (adulthood) and progression (aging) and the impact of high-fat diet (HFD) and intranasal insulin (INI). Glucose metabolism (18FDG-PET), tissue radiodensity (CT), liver and W/BAT histology, BAT-thermogenic markers were analyzed. 16S-RNA sequencing and mass-spectrometry were performed in adult (8 months) and aged (14 months) 3xTg-AD mice with a high-fat or control diet. Generalized and HFD resistant deficiency of lipid accumulation in both liver and W/BAT, hypermetabolism in WAT (adulthood) and BAT (aging), abnormal cytokine-hormone profiles, and liver inflammation were observed in 3xTg mice; INI could antagonize all these alterations. Specific gut microbiota-metabolome profiles correlated with a significant disruption of the gut-microbiota-liver-adipose axis in AD mice. In conclusion, fat dystrophy in liver and adipose depots contributes to AD progression, and associates with altered profiles of the gut microbiota, which candidates as an appealing early target for preventive intervention.This study was conducted within the JPI-HDHL-INTIMIC Knowledge Platform of Food, Diet, Intestinal Microbiomics, and Human Health (sub-project no. KP-778 MISVILUPPO, Italian Ministry of Agricultural, Food and Forestry Policies, Ministry Decree 23092/7303/19), and the JPI-HDHL-INTIMIC Joint Transnational Research program (project no. INTIMIC-085 GUTMOM, Italian Ministry of Education, University and Research, Ministry Decree no. 946/2019). The funders had no role in study design, data collection and analysis, or preparation of the manuscript. Projects supported by the Joint Action “European Joint Programming Initiative: A Healthy Diet for a Healthy Life (JPI HDHL)” are funded by the respective national/regional funding organisations: Fund for Scientific Research (FRS—FNRS, Belgium); Research Foundation—Flanders (FWO, Belgium); INSERM Institut National de la Santé et de la Recherche Médicale (France); Federal Ministry of Food and Agriculture (BMEL) represented by Federal Office for Agriculture and Food (BLE, Germany); Ministry of Education, University and Research (MIUR), Ministry of agricultural, food, and forestry policies (MiPAAF), National Institute of Health (ISS) on behalf of the Ministry of Health (Italy); the National Institute of Health Carlos III (Spain); The Netherlands Organisation for Health Research and Development (ZonMw, The Netherlands), Austrian Research Promotion Agency (FFG) on behalf of the Austrian Federal Ministry for Education, Science, and Research (BMBWF), Ministry of Science and Technology (Israel), Formas (Sweden). DM gratefully acknowledges funding from the Ministry of Science and Innovation of Spain (ACPIN2017-117 and PID2019-108973RB-C22).Peer reviewe

Treatment of chronic hepatitis B: from research to clinical practice via the consensus conferences

The aim of antiviral therapy of chronic hepatitis B is to control Hepatitis B Virus (HBV) replication and to cure liver disease avoiding the progression of chronic hepatitis to cirrhosis and the end stage complications of cirrhosis. HBeAg/anti-HBe seroconversion is the hallmark of response in hepatitis B "e" antigen (HBeAg) positive patients. In the patients with antibody against HBeAg (anti-HBe positive) the combination of HBV DNA and anti-HBc IgM tests provides adequate diagnostic accuracy. Patients with biochemical and/or histological disease activity are eligible to therapy. The drug choice is based on age, disease severity, risk of complications, side effects and compliance, particularly in anti-HBe positive patients where prolonged treatment is needed. Interferon (5-6 MU daily or 9-10 MU thrice weekly for 4-6 months) is the first line therapy for HBeAg positive patients and (5-6 MU thrice weekly for 12-24 months) for anti-HBe positive patients. When IFN is contraindicated or ineffective, Lamivudine (100 mg) or Adefovir Dipivoxil (10 mg) are given as long as 4-6 months after HBeAg/anti-HBe seroconversion or for long-term treatments in HBeAg positive non-responders and anti-HBe positive patients. Patients with more advanced forms of cirrhosis and portal hypertension are to be treated within liver transplantation programs. Fifteen to 30% of treated patients achieve sustained response and more than 60% of them experience long-term disease remission during therapy. In perspectives, currently available molecular and immunologic tools and modelling of viral dynamics will help to address the therapy issue with more complex, efficacious and individually tailored treatment schedules

Pathogenic significance of HBV variants

Paper presented at the International conference on Hepatitis BAvailable from Centro de Informacion y Documentacion Cientifica CINDOC. Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai