Search

Clinical elements differentiating enteropathy due to angiotensin II-receptor-blockers (ARBs-E) from coeliac disease (CD) are poorly defined. The histopathological features on duodenal and gastric biopsies in these patients still need to be investigated. To describe the clinical phenotype of ARBs-E in comparison to CD, and the histological findings of gastric and duodenal biopsies in ARBs-E. Clinical data of patients with ARBs-E and CD diagnosed between 2013 and 2020 were retrospectively reviewed. Baseline presenting symptoms and demographics were compared (Fisher's exact test and t -test). Gastric and duodenal histology in ARBs-E were revised by two independent pathologists. 14 ARBs-E and 112 CD patients were enroled. Weight loss (p < 0.01), acute onset of diarrhoea (p < 0.01), hospitalization (p < 0.01), and older age at diagnosis (p < 0.01) were more common in ARBs-E. Duodenal histology in ARBs-E showed intraepithelial lymphocytosis in 71%, increased mucosal eosinophilic count in 57%, with preserved neuroendocrine, Paneth and goblet cells in all patients. Gastric histologic lesions at baseline, including lymphocytic gastritis, eosinophilic gastritis, chronic active gastritis, and metaplastic atrophic gastritis patterns were observed in 73% of patients, without Helicobacter pylori infection. ARBs-E showed a severe clinical phenotype, often requiring hospital admission. Gastric involvement at diagnosis is very common, and this could further support this diagnosis. [ABSTRACT FROM AUTHOR]

Duodenal dysbiosis has been suggested to possibly influence the clinical manifestations of coeliac disease (CD), both at onset and when symptoms persist despite a gluten-free diet (GFD). To evaluate the relationship between duodenal microbiota composition and: i) clinical phenotype of untreated CD (UCD); ii) presence and type of persistent symptoms despite a satisfactory serological and histological response to a strict GFD. Duodenal microbiota was analyzed by 16S rRNA sequencing and compared with i) clinical features in 12 adult UCD patients; ii) presence/absence and type of persistent symptoms (diarrhea-predominant vs. non-diarrhea predominant) in 25 adult treated coeliac patients (TCD) on a strict GFD. UCD with iron deficiency anemia (IDA) had a pro-inflammatory shift in their duodenal microbiota (reduction of Firmicutes, p = 0.03; increase of beta-Proteobacteria, p = 0.02) than those without IDA. TCD with persistent diarrhea showed a reduction of Actinobacteria (p = 0.03) and Rothia spp (p = 0.046) compared to TCD suffering from other type of persistent symptoms. A distinctive duodenal microbiota profile is associated with IDA in UCD, and diarrhea-predominant persistent symptoms in TCD. Clinical interventions may include reconsidering patients presenting with IDA as a specific disease subtype, and dietary rebalancing if diarrhea persists despite histological response to a GFD. [ABSTRACT FROM AUTHOR]

The natural history of patients with potential autoimmune gastritis (AIG), defined by the presence of serum anti-parietal cell antibody (PCA) positivity and no gastric histopathological alterations, is unknown. We therefore aimed to assess the natural history and clinical correlates of potential autoimmune gastritis (AIG). In 2000–2019, we enrolled potential AIG patients by monitoring once a year (±6 months) histopathological evolution into overt AIG, defined as the occurrence of atrophy in the oxyntic mucosa. Factors affecting disease progression were assessed. Fifty-one potential AIG patients (median age 57 years, IQR 43–73, F:M ratio 1.7:1) were monitored for up to 15 years (median 6 years, IQR 3–8). Of them, 24 (47.1%) evolved into overt AIG in a median time of 2 years (IQR 2–4.5). Having a concomitant autoimmune disorder (HR 4.09, 95% CI 1.52–11.00; p = 0.005), but not older age (HR 1.00, 95% CI 0.45–2.22; p = 0.992) and female sex (HR 1.19, 95% CI 0.51–2.78; p = 0.395), was associated with evolution into overt AIG. Roughly one in two potential AIG patients will evolve into overt AIG over a median time of two years, especially those with a concurrent autoimmune disorder. [ABSTRACT FROM AUTHOR]

Chronic atrophic gastritis (CAG) is an underdiagnosed condition characterised by translational features going beyond the strict field of gastroenterology as it may manifest itself by a variable spectrum of gastric and extra-gastric symptoms and signs. It is relatively common among older adults in different parts of the world, but large variations exist. Helicobacter pylori -related CAG [multifocal] and autoimmune CAG (corpus-restricted) are apparently two different diseases, but they display overlapping features. Patients with cobalamin and/or iron deficiency anaemia or autoimmune disorders, including autoimmune thyroiditis and type 1 diabetes mellitus, should be offered screening for CAG. Pepsinogens, gastrin-17, and anti- H. pylori antibodies serum assays seem to be reliable non-invasive screening tools for the presence of CAG, helpful to identify individuals to refer to gastroscopy with five standard gastric biopsies in order to obtain histological confirmation of diagnosis. Patients with CAG are at increased risk of developing gastric cancer, and they should be estimated with histological staging systems (OLGA or OLGIM). H. pylori eradication may be beneficial by modifying the natural history of atrophy, but not that of intestinal metaplasia. Patients with advanced stages of CAG (Stage III/IV OLGA or OLGIM) should undergo endoscopic surveillance every three years, those with autoimmune CAG every three-five years. In patients with CAG, a screening for autoimmune thyroid disease and micronutrient deficiencies, including iron and vitamin B 12 , should be performed. The optimal treatment for dyspeptic symptoms in patients with CAG remains to be defined. Proton pump inhibitors are not indicated in hypochlorhydric CAG patients. [ABSTRACT FROM AUTHOR]

Professions distinguished by repeated vocal stress carry a high risk of developing gastroesophageal reflux symptoms (GERS) which may affect vocal performance. To investigate the prevalence of self-reported GERS in professional opera soloists. A validated questionnaire regarding self-reported GERS (heartburn, regurgitation, chest pain, dysphagia, hoarseness, and cough) and lifestyle habits was administered to 116 professional opera soloists (mean age 34.1 ± 7.3 years, F:M ratio 1:1.1). Age and sex-matched opera choristers and control subjects were used as control. Prevalence rate ratios (PRRs) adjusted for confounding factors were evaluated. Among GERS, belching (33.6%), heartburn (19.8%), and dysphagia (15.5%) were the most commonly reported by soloists. In particular, a higher risk of heartburn (PRR 2.61, 95% CI 1.45–4.69) and dysphagia (PRR 2.58, 95% CI 1.31–5.10) was reported in soloists as compared to choristers. The prevalence of obesity and late dinner was higher in both choristers and soloists in comparison to the population sample (p < 0.001). GERS was more common among soloists who received pharmacologic treatment and their prevalence was unrelated to the years of singing activity. Professional opera soloists, regardless of the length of their career, are predisposed to developing GERS. Physicians should encourage patients to correct preventable risk factors. A prolonged pharmacological treatment might be needed. [ABSTRACT FROM AUTHOR]

Abstract Background Inflammatory bowel disease (IBD) is associated with neuroendocrine cell hyperplasia. Aims We investigated neuroendocrine cells in J-pouches of patients with ulcerative colitis undergoing restorative proctocolectomy and ileal pouch-anal anastomosis. Methods Sections from pouch biopsies of 17 patients and ileal biopsies of 17 active IBD patients and 16 controls were processed by immunohistochemistry for chromogranin A (CgA) and serotonin. Mucosal tryptophan hydroxylase (TpH)-1 and serotonin-selective reuptake transporter (SERT) transcripts were measured by quantitative RT-PCR. TpH-1 and SERT transcripts were detected in pouch biopsies cultured with infliximab or its isotype control, while interleukin (IL)-6 and IL-8 were measured in biopsy supernatants. Results A significant increase in CgA-positive cells and serotonin-positive cells was observed in both pouch and IBD ileum compared to control ileum. Significantly raised transcripts of TpH-1, but not SERT, were found in IBD ileum in comparison to control ileum, with no significant difference between pouch and IBD ileum. Infliximab had no influence on ex vivo pouch expression of TpH-1 and SERT, nor on the production of IL-6 and IL-8. Conclusion We here demonstrated neuroendocrine cell hyperplasia in pouch mucosa. Further studies are needed to clarify the pathophysiological implication of this finding. [ABSTRACT FROM AUTHOR]

Frailty, which is a syndrome that encompasses losses in physical, psychological and social domains, is responsible for enhanced vulnerability to endogenous and/or exogenous stressors. Frailty is a public health problem for an ageing society; however, it is poorly understood and often under-recognised in clinical settings. In particular, the impact of frailty on either intestinal functions, i.e. immune response, permeability, and absorption, or gut microbiota composition is as yet mostly unexplored. A better comprehension of the intestinal dysfunction occurring in the elderly would help in clarifying the mechanisms predisposing frail patients to a higher risk of infectious or inflammatory events. Moreover, recent evidence suggests that senescence-induced perturbations of the gut–brain axis are involved in the neuroinflammation process, thus raising the hypothesis that preserving gut permeability and preventing frailty-related changes in the microbiota composition might reduce the susceptibility to develop neurodegenerative disorders. In this review, we highlight the current insights concerning the relationship between frailty, intestinal functions, microbiota, and gut–brain axis. [ABSTRACT FROM AUTHOR]

The progressively growing knowledge of the pathophysiology of a number of immune-mediated gastrointestinal and liver disorders, including autoimmune atrophic gastritis, coeliac disease, autoimmune enteropathy, inflammatory bowel disease, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis and autoimmune pancreatitis, together with the improvement of their detection methods have increased the diagnostic power of serum antibodies. In some cases – coeliac disease and autoimmune atrophic gastritis – they have radically changed gastroenterologists’ diagnostic ability, while in others – autoimmune hepatitis, inflammatory bowel disease and autoimmune pancreatitis – their diagnostic performance is still inadequate. Of note, serum antibody misuse in clinical practice has raised a number of controversies, which may generate confusion in the diagnostic management of the aforementioned disorders. In this review, we critically re-evaluate the usefulness of serum antibodies as biomarkers of immune-mediated gastrointestinal and liver disorders, and discuss their pitfalls and merits. [ABSTRACT FROM AUTHOR]

Refractory celiac disease is characterized by mucosal damage in patients with celiac disease despite a gluten-free diet. Little is known about the mechanisms that cause persistent intestinal inflammation in these patients. We performed a case-control study of 17 consecutive patients diagnosed with refractory celiac disease from 2001 through 2014 (median age, 51 y; 10 women) and 24 patients with uncomplicated celiac disease (controls) to determine whether refractory disease is associated with infection by lymphotropic oncogenic viruses. We performed real-time PCR analyses of duodenal biopsy samples from all patients to detect Epstein–Barr virus (EBV), human herpesvirus-8, and human T-cell lymphotropic virus-I, -II, or -III. We used in situ hybridization and immunohistochemical analyses to identify infected cells and viral proteins. We did not detect human herpesvirus-8 or human T-cell lymphotropic viruses in any of the biopsy specimens. However, 12 of 17 (70.5%) biopsy specimens from patients with refractory celiac disease were positive for EBV, compared with 4 of 24 (16.6%) biopsy specimens from controls ( P < .001). EBV was detected in inflammatory cells and enterocytes. An analysis of latency- and replication-associated proteins confirmed active infection. Further studies are needed to determine whether EBV infection contributes to the pathogenesis of refractory celiac disease and enteropathy-associated T-cell lymphoma. [ABSTRACT FROM AUTHOR]

Background Immune mechanisms have been implicated in nonceliac gluten sensitivity (NCGS), a condition characterized by intestinal and/or extraintestinal symptoms caused by the ingestion of gluten in non-celiac/non-wheat allergic individuals. Aims We investigated innate and adaptive immunity in self-reported NCGS versus celiac disease (CD). Methods In the supernatants of ex vivo -cultured duodenal biopsies from 14 self-reported NCGS patients, 9 untreated and 10 treated CD patients, and 12 controls we detected innate cytokines – interleukin (IL)-15, tumor necrosis factor-α, IL-1β, IL-6, IL-12p70, IL-23, IL-27, IL-32α, thymic stromal lymphopoietin (TSLP), IFN-α-, adaptive cytokines – interferon (IFN)-γ, IL-17A, IL-4, IL-5, IL-10, IL-13-, chemokines – IL-8, CCL1, CCL2, CCL3, CCL4, CCL5, CXCL1, CXCL10-, granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF). Results Mucosal innate and adaptive cytokines, chemokines and growth factors did not differ between self-reported NCGS, treated CD and controls. On the contrary, IL-6, IL-15, IL-27, IFN-α, IFN-γ, IL-17A, IL-23, G-CSF, GM-CSF, IL-8, CCL1 and CCL4 were significantly higher in untreated CD than in self-reported NCGS, treated CD and controls, while TSLP was significantly lower in untreated CD than in self-reported NCGS, treated CD and controls. Conclusion In our hands, patients with self-reported NCGS showed no abnormalities of the mucosal immune response. [ABSTRACT FROM AUTHOR]

Background The relationship between gluten ingestion and gastrointestinal tract function is a matter of debate. Aim We analysed the effect of gluten on gastric and gallbladder emptying and intestinal fermentation in healthy volunteers. Methods Ultrasound measurement of gastric and gallbladder emptying after both gluten-containing and gluten-free meals was performed in 18 volunteers (8 women, age 25.0 ± 2.5 years; BMI 22 ± 1.9). Breath hydrogen excretion after a gluten-containing meal, a gluten-free meal and a gluten-free meal with added gluten powder was measured in 16 volunteers (10 women, age 25.2 ± 2.7 years; BMI 22 ± 1.8). The severity of symptoms was monitored. Results Gluten presence in the meals was not recognised. Gastric emptying time was 81.6 ± 13.8 min after gluten-containing and 73.9 ± 21.6 min after gluten-free meals ( p = 0.11). Percentage ejection fraction after gluten-containing meals was 60 ± 9% and 60.6 ± 6% after gluten-free meals ( p = 0.68). Peak and cumulative hydrogen excretion were significantly higher after gluten-containing than after gluten-free meals (peak: 12.5 ± 7.3 vs 6.5 ± 5.1 parts-per-million, p < 0.01; and cumulative: 2319 ± 1720 vs 989 ± 680 parts-per-million/minute, respectively; p < 0.01). Adding gluten powder to the gluten-free meal did not modify fermentation. Symptoms were mild and not different after the meals. Conclusions In healthy volunteers, gluten may induce gastrointestinal alterations. Further studies are needed to clarify which patients could benefit from dietary modification. [ABSTRACT FROM AUTHOR]

Abstract: Background: Health-related quality of life is an important measure of treatment outcome; its evaluation requires the use of internationally validated ad hoc questionnaires. The McMaster Inflammatory Bowel Disease Questionnaire (IBDQ) is the most used specific instrument. Aim: To assess the validity and reliability of the Italian translation of the IBDQ. Methods: The IBDQ underwent forward and backward translation; 13 patients were enrolled for cognitive testing of the Italian version to increase clarity. For field testing, 113 patients (65 with Crohn''s disease and 48 with ulcerative colitis) completed both the IBDQ and the generic instrument 36-item Short Form Health Survey scale (SF-36). Results: Data quality was optimal with high completeness and low floor and ceiling effect. Item internal consistency was satisfied for 100% of patients, while discriminant validity showed a few items with higher correlations with other scales. Cronbach''s alpha coefficient was 0.96. Test–retest correlations indicated good reliability (Pearson R 0.81). Exploratory factor analysis indicated that the original grouping of the item was suboptimal. The score proved sensitive to disease activity, gender and quality of life as measured by the SF-36. Conclusions: The Italian translation of the McMaster Inflammatory Bowel Disease Questionnaire sounds natural and is easy to understand. A field test gave results comparable to other international validations, supporting its use in cross-national surveys. [Copyright &y& Elsevier]

Purpose: The current TNM classification is still unsatisfactory for collecting all the prognostic information from the clinical presentation of early gastric cancer: "T" is limited to two levels, the classes of "N" are still wide and "M" is generally absent.Patients and Methods: This study involved 99 patients who underwent radical gastric resection for early gastric cancer. Clinical and histological parameters were prognostically analyzed for both observed and relative survival. Univariate and multivariate analyses were applied to the proportional hazards model.Results: Number of metastatic lymph nodes and measure of the largest diameter of the tumor were the only independent prognosticators of observed and relative survival. Their similar relative hazards allowed an additive use of them in the N class. Two cut-off values of this composite clinical parameter are proposed for a good discrimination of the relative survival.Discussion: The number of metastatic lymph nodes is the cornerstone of the current TNM system and was confirmed as adequate. The possibility of adding tumor size to the number of the involved lymph nodes improves and amplifies the prognostic ability, which is presently limited by the rarity of lymph node involvement and the small number of the lymph nodes usually involved. [ABSTRACT FROM AUTHOR]

Background & Aims: The Marsh–Oberhuber classification of duodenojejunal mucosal lesions is currently used for celiac disease. A more simplified classification, which is based on 3 villous morphologies (A, non-atrophic; B1, atrophic, villous-crypt ratio <3:1; B2, atrophic, villi no longer detectable) and an intraepithelial lymphocyte count of >25/100 enterocytes, has recently been proposed. The aim of the study was to asses the interobserver agreement between different pathologists in classifying celiac disease lesions according to both Marsh–Oberhuber and the new classification system. Methods: Sixty patients were selected for the study: 10 subjects without celiac disease, 13 celiac patients with normal villi but a pathologic increase in intraepithelial lymphocytes >25/100 and hyperplastic crypts, and 37 patients with celiac disease with villous atrophy. Sixty slides were sent to 6 pathologists, who were blinded to each other and were not given any clinical information. Each pathologist received the set of biopsy specimens on 2 separate occasions and had to evaluate them according to both grading systems in a random order. The kappa statistic was used to assess agreement between each pair of pathologists. Results: Overall, mean kappa values were 0.35 (fair) for the Marsh–Oberhuber classification versus 0.55 (moderate) for the new classification system. Conclusions: The new classification for duodenal pathology in celiac disease gives better interobserver agreement compared with the more cumbersome Marsh–Oberhuber classification and contributes to the validity of diagnosis in celiac disease. [Copyright &y& Elsevier]

Background & Aims: Bloating represents a frequent gastrointestinal symptom, but the pathophysiologic mechanism responsible for its onset is still largely unknown. Patients very frequently attribute the sensation of bloating to the presence of excessive bowel gas, but not all patients with gas-related symptoms exhibit increased intestinal production of gas. It is therefore possible that other still unrecognized mechanisms might contribute to its pathophysiology. Our aim was to evaluate whether a subgroup of patients affected by functional abdominal bloating presents hypersensitivity to colonic fermentation. Methods Sixty patients affected by functional gastrointestinal disorders (11 functional bloating, 36 constipation-predominant, and 13 diarrhea-predominant irritable bowel syndrome) and moderate to severe bloating took part in the study. Twenty sex- and age-matched healthy volunteers were enrolled as a control group. All the subjects underwent a preliminary evaluation of breath hydrogen excretion after oral lactulose. Then, on a separate day, an evaluation of sensitivity thresholds at rectal level was performed with a barostat before and after the induction of colonic fermentation with oral lactulose. A control test with electrolyte solution was also performed. Results Both breath hydrogen excretion and mouth-to-cecum transit time did not differ between the 4 groups studied. Neither electrolyte solution nor lactulose modified sensitivity thresholds in healthy volunteers. In low hydrogen producers, basal perception and discomfort thresholds were similar to high hydrogen producers, but after lactulose both perception and discomfort thresholds were significantly reduced only in low hydrogen producers. Conclusions A subgroup of patients with functional gastrointestinal disorders and moderate to severe bloating might have hypersensitivity to products of colonic fermentation. [Copyright &y& Elsevier]

Background & Aims: In view of the excellent quality of the images obtained and its magnification capability, videocapsule endoscopy was proposed as a promising tool to evaluate the degree of duodenal villous atrophy. We studied whether the capsule can discriminate different degrees of mucosal damage caused by different conditions; we also evaluated interobserver and intraobserver variability in the assessment of villous atrophy with the capsule. Methods: Thirty-two patients underwent both gastroscopy with multiple duodenal biopsies and videocapsule endoscopy. Twenty-six had different forms of celiac disease with different stages of villous atrophy; 5 patients had irritable bowel syndrome and 1 had Crohn’s disease. Videocapsule findings were evaluated blindly by 3 observers. Histologic Marsh criteria and a specifically developed classification of videocapsule mucosal patterns were used to compare videocapsule findings and histology. Results: The study of the correlation between videocapsule and histologic findings showed a Kappa statistic of .45, .49, and .51 for observers 1, 2, and 3, respectively. The sensitivity was 90.5% for observer 1 and 95.2% for observers 2 and 3; the specificity was 63.6% for all observers. Conclusions: Videocapsule findings regarding the degree of intestinal mucosal atrophy show only moderate agreement with the histologic pattern; they have a very high sensitivity but a disappointing specificity. This method therefore cannot be proposed as an alternative to traditional biopsy examinations, but it suggests that a duodenal biopsy examination should be performed when an atrophic mucosal pattern is observed in patients undergoing videocapsule examination for other reasons. [Copyright &y& Elsevier]

Background & Aims: We investigated the prevalence of functional hyposplenism in autoimmune disorder (AID)-associated and complicated celiac disease (CD). In addition, because the association between hyposplenism and overwhelming infections caused by Streptococcus pneumoniae in patients with CD is well known, we investigated whether immunoglobulin (Ig)M memory B cells, which are responsible for protection against infections by encapsulated bacteria and require the spleen for their generation and/or survival, mirror the reduced splenic function in CD. Methods: Peripheral blood samples were collected from 73 adult CD patients (27 with AID, 36 without AID, and 10 with CD-related complications including enteropathy-associated T-cell lymphoma, refractory sprue, and ulcerative jejunoileitis). Thirty-four non-CD patients with AID, 35 healthy volunteers, and 29 splenectomized patients also were studied. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function, and flow cytometry was performed to analyze peripheral blood B cells. Results: A significantly higher risk for hyposplenism was found in AID-associated CD (59%) and complicated CD (80%) than in uncomplicated CD without AID (19%). In AID-associated CD, the degree of splenic function did not correlate to the duration of gluten-free diet. In AID-associated and complicated CD, the frequency of circulating IgM memory B cells was significantly lower than in CD patients without AID or healthy subjects. A significant inverse correlation between IgM memory B cells and pitted red cells was found in all 73 CD patients. Conclusions: The prevalence of splenic hypofunction is increased in CD with AID and in complicated CD, and is not related to the duration of gluten-free diet. IgM memory B cells are reduced in AID-associated and complicated CD. This defect, which is related to the impairment of splenic function, might predispose hyposplenic CD patients to infections by encapsulated bacteria. [Copyright &y& Elsevier]

Coeliac disease predisposes to metabolic osteopathy. The entity of bone loss is higher in patients with malabsorption at diagnosis but it is also present in asymptomatic or poorly symptomatic patients, occurring in roughly half of them. Calcium malabsorption and the release of proinflammatory cytokines, activating osteoclasts, represent the main mechanisms responsible for bone derangement. In coeliacs, the presence of an increased fracture risk was recently questioned and its importance on clinical grounds was reconsidered, in view of the fact that gluten-free diet generally improves bone mass and, consequently, reduces fracture risk. However, gluten-free diet rarely normalizes bone mass and the co-administration of mineral active drugs may be useful in a subgroup of coeliacs. [Copyright &y& Elsevier]

Background & Aims: Autoimmune atrophic gastritis (AIG) is characterized by immune-mediated chronic inflammation of the gastric body and fundus, leading to hypo-achlorhydria and vitamin B12 deficiency. We analyzed the clinical features of AIG and sought to identify factors that might be used in diagnosis. Methods: We collected and analyzed clinical data from 99 consecutive patients (age, 59 ± 17 y) who were diagnosed with AIG, based on histologic factors and the presence of autoantibodies against gastric parietal cells. Results: Clinical factors that led to a diagnosis of AIG included hematologic findings related to vitamin B12 deficiency (n = 37), incidental histologic evidence in gastric biopsy specimens (n = 34), immune disorders (n = 18; 9 were celiac disease), neurologic symptoms (n = 6), and a family history of AIG (n = 4). Conclusions: Based on an analysis of 99 consecutive patients with AIG, this disorder is not solely a condition of the elderly. Other features to look for in making a diagnosis of AIG include vitamin B12 deficiency, histologic factors, and immune disorders. [ABSTRACT FROM AUTHOR]

Background and aims Blood lysosomal acid lipase (LAL) is reduced in non-alcoholic steatohepatitis, which is the major cause of cryptogenic cirrhosis (CC); few data on LAL activity in CC do exist. We investigated LAL activity in a cohort of patients with liver cirrhosis. Methods This is a multicentre cohort study including 274 patients with liver cirrhosis of different aetiology from 19 centres of Internal Medicine, Gastroenterology and Hepatology distributed throughout Italy. Blood LAL activity (nmol/spot/h) was measured with dried blood spot extracts using Lalistat 2. Results Overall, 133 patients had CC, and 141 patients had cirrhosis by other causes (61 viral, 53 alcoholic, 20 alcoholic + viral, 7 autoimmune). Mean age was 64.2 ± 13.4 years, and 28.5% were women. Patients with CC were older compared to other aetiology-cirrhosis, with a lower Child-Turcotte-Pugh (CTP, p =0.003) and MELD ( p =0.009) score, and a higher prevalence of cardio-metabolic risk factors and previous ischemic events. In the whole cohort, median LAL activity value was 0.58 nmol/spot/h, 0.49 and 0.65 in the groups of CC and known-aetiology cirrhosis, respectively ( p =0.002). The difference remained significant after adjustment for white blood cells count ( p =0.001). Multivariable linear regression analysis showed that CC ( vs. known aetiology, Beta = −0.144, p =0.018), platelet count (Beta = 0.398, p < 0.001) and CTP score (Beta = −0.133, p =0.022) were associated with log-LAL activity. Similar results were found using MELD as covariate. Conclusions We found a marked reduction of LAL activity in patients with cryptogenic cirrhosis compared to the other known aetiologies. A prospective study will clarify the role of LAL in chronic liver diseases. [ABSTRACT FROM AUTHOR]

Recent progresses in the immune mechanisms implicated in chronic inflammatory disorders have led to a more in-depth knowledge of the pathogenesis of autoimmune diseases of the gastrointestinal tract, including autoimmune atrophic gastritis, celiac disease, autoimmune enteropathy and ulcerative colitis. While the pathogenic role of specific circulating autoantibodies, i.e., respectively anti-parietal cell, anti-tissue transglutaminase, anti-enterocyte and anti-neutrophil cytoplasmic, is still controversial, some common T-cell mediated mechanisms for inflammation – increase in T helper cell type 1/type 17 pro-inflammatory cytokines- or losing self-tolerance-abnormal regulatory T cell function – are recognized as crucial mediators of the tissue damage causing atrophy of the stomach mucosa in autoimmune atrophic gastritis, villous flattening of the small bowel in celiac disease and autoimmune enteropathy, and mucosal ulceration of the colon in ulcerative colitis. This review deals with novel advances in the immunological bases of the aforementioned autoimmune gastrointestinal disorders, and it also highlights immune mechanisms of progression from chronic inflammation to cancer and implications for new therapeutic targets. [ABSTRACT FROM AUTHOR]