Polyomavirus BK replication in renal transplant recipients: combined monitoring of viremia and VP1 mRNA in urine

Introduction. Human polyomavirus BK (BKV) is worldwide distributed, with a seroprevalence rate of 70–90% in the adults. Following primary infection, BK remains latent in the renourinary tract as the epidemiologically most relevant latency site, and in B cell, brain, spleen and probably other tissues. Reactivation may occur in both immunocompetent subjects and immunocompromised patients. In renal transplantation, in the context of intense immunosuppression, viral replication may determine BKV-associated nephropathy (BKVAN) with interstitial nephritis and/or ureteral stenosis in 1–10% of the patients and leading to graft failure and return to haemodialysis in 30 to 80% of the cases (5). Screening of BKV replication represents the basic strategy to predict early the onset of BKVAN and may allow for earlier intervention with reduced allograft loss (3, 4). Nowadays, replication of BKV is monitored by quantification of BKV-DNA in serum and urine (2). The aim of this study was to evaluated the role of BKV VP1 mRNA in urine as a marker of viral replication in renal transplant recipients

Efficacy of a preparation based on calcium butyrate, bifidobacterium bifidum, bifidobacterium lactis, and fructooligosaccharides in the prevention of relapse in ulcerative colitis: A prospective observational study

Several compounds based on short chain fatty acids and/or probiotics/prebiotics have shown promising results in the therapy of ulcerative colitis (UC), possibly due to its key role in restoring gut homeostasis as well as intestinal barrier integrity. Here, we investigated the efficacy of a patented preparation based on calcium butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and fructooligosaccharides (FEEDColon(®), Princeps, Cuneo, Italy) in maintaining remission and improving subjective symptoms and inflammatory indices in patients with UC receiving 5-ASA therapy. A total of 42 patients were prospectively recruited and randomized in 21 patients receiving combination therapy with mesalamine (5-ASA) plus FEEDColon(®) and 21 patients treated with standard 5-ASA therapy. Patients were assessed at baseline, at 6-month, and 12-month follow-up (FU). Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12-month FU) was reached by 32 (76%) patients: 20 (95%) among those treated with 5-ASA + FeedColon(®), and 12 (57%) among those treated with 5-ASA only (p = 0.009). Consistently, patients treated with combination therapy improved subjective symptoms (quality of life, abdominal pain, and stool consistency) and reduced FC values, while those treated with 5-ASA alone, improved neither subjective symptoms nor FC during the FU. In conclusion, FEEDColon(®) supplementation appears to be a valid add-on therapy for the maintenance of remission in patients with UC. Further multicentre, placebo-controlled, double-blind clinical trials are needed to validate our results on larger cohorts of patients with UC

POS0230 INTESTINAL MICROBIOTA CHANGES TNF-INHIBITORS INDUCED IN IBD-RELATED SPONDYLOARTHRITIS

Background:the close relationship between joints and gut inflammation has long been known and several data suggest that the dysbiosis could represents the link between Spondyloarthritis (SpA) and Inflammatory Bowel Diseases (IBD). To date, the manipulation of the intestinal microbiota is considered the key to the cure or control of the natural history of several pathologies sustained or favored by dysbiosis. The introduction of biologic drugs, in particular Tumor Necrosis Factor inhibitors (TNFi), revolutionized the management of both these diseases, thanks to the strong inhibition of inflammation and partially indirectly with mechanisms not yet fully clarified. While the impact of conventional drugs on gut microbiota is well known poor data are available about TNFi.Objectives:to investigate the impact of TNFi on gut microbiota.Methods:we included CD or UC patients fulfilling criteria for axial or peripheral SpA (ASAS 2009) on a typical Mediterranean diet, naïve to biologics needing TNFi. Clinical history, physical examination, instrumental examinations, biochemical examination including C-reactive protein (CRP), erhytrocyte sedimentation rate (ESR), HLA-B27 and fecal calprotectin at the baseline and after 6 months were performed. TNFi included infliximab and adalimumab. Fecal samples were collected by patients themselves by 24 hours before the start of the therapy. The processing was performed through metagenomic NGS (next generation sequencing) including the amplification of the V3 and V4 regions of the 16S (V3 and V4) and sequencing on the Illumina MiSeq platform. All patients received the treatment at least until week 24. Clinical disease indices included Visual Analogue Scale (VAS)-pain and Visual Analgue Scale(VAS)-disease activity for all patients, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for axial involvement, clinical disease activity index (CDAI) and Health Assessment Questionnaire-Disability Index (HAQ-DI) for peripheral involvement, Harvey-Bradshaw Index for CD (HBI), or partial Mayo (pMAYO) score for UC, were assessed at baseline and at the end of the study. The study was approved by the ethics committee (approval code 0056924).Results:we evaluated 20 patients affected by enteropatic arthritis, naïve for biologic drugs, treated with TNFi. After six months of therapy we observed a significant increase in Lachnospiracae family (Δ +10.3, p 0.04) and in Coprococcus genus (Δ +2.8, p 0.003). We also observed a decrease trend in Proteobacteria (Δ -8.0 p 0.095) and Gammaproteobacteria (Δ -9, p 0.093) and an increase trend in Clostridia (Δ +8.2 p 0.083). We didn't find differences between TNFi responders (SpA improvement or IBD remission achieved) and not responders in terms of alpha and beta-diversity.Conclusion:the decrease of Proteobacteria and the increase of Lachnospiraceae and Coprococcus is consistent with the hypothesis that TNFi therapy, by decreasing inflammation, tends to restore the intestinal eubiosis. However further studies on larger cohort incuding the evaluation of gut virota and micobiota will be necessary to definitively clarify the effects of TNFi on the composition and function of the gut microbiota.References:[1]Bazin T et al. Sci Rep. 2018;8(1):5446.[2]Aden K et al. Gastroenterology. 2019;157(5):1279-1292.e11.Table 1.Comparison between clinical variables between baseline and T6 (six months)Clinical variablesT0T6P_valueFecal Calprotectin(μg/g)- median (IQR)207.5(125.5-446.2)81(50-197.2)0.004CRP(mg/L)- median(IQR)8.2(4.8-20.8)2.9(1-4)0.001ESR(mm/h)- median(IQR)21.5(10.8-34)11(7.8-21)0.003VAS_pain- median(IQR)50(38.8-60)35(10-42.5)0.001VAS_disease- median(IQR)50(38.8-50)37.5(25-42.5)0.006HAQ- mediana(IQR)0.6(0.1-0.8)0.2(0.1-0.6)0.004BASDAI_score- median(IQR)5.2(4.1-5.6)2.8(2.5-4.3)0.013CDAI_activity- median(IQR)13(10.5-16)7(5.2-11)0.004IBD activity n(%) - 011 (55%)20 (100%)0.174IBD activity n(%) - 16 (30%)0 (0%)IBD activity n(%) - 22 (10%)0 (0%)IBD activity n(%) - 31 (5%)0 (0%)Disclosure of Interests:None declared

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

Abstract Background: Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. Methods: Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. Results: 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. Conclusions: Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history. Keyword: Celiac disease, Complications, EATL, Prognosis, Glutens, Gluten-free die