Histological Improvement Research Articles

Effect of Canagliflozin Alone and in Combination with Metformin on Ovarian Histology of a Polycystic Ovary Syndrome Rat Model

<p><strong>Background and Objective:</strong> Canagliflozin reduces insulin resistance in diabetics and is hypothesized to produce a beneficial effect in polycystic ovarian syndrome (PCOS). Therefore, this study is planned to compare the effects of canagliflozin and metformin alone and in combination on ovarian histology of rat models with letrozole-induced PCOS.</p>
 <p><strong>Methods:</strong> It was a randomized experimental study on Sprague Dawley rats. A total of N = 40 female rats were divided randomly into six groups (A-F). With the exception of normal control group A, rats were given letrozole 1 mg/kg daily for 21 days till PCOS was induced. Group B was disease control, while rats in groups C-F were administered canagliflozin (10 mg/kg), metformin (100 mg/kg), a combination of canagliflozin (10 mg/kg) with metformin (100 mg/kg), and combination of canagliflozin (5 mg/kg) with metformin (50 mg/kg), respectively. Animals were sacrificed on the 48th day. Ovaries and uterus were removed, weighed, and processed for further histopathological analysis.</p>
 <p><strong>Results:</strong> All treatment groups showed significant improvement in ovarian histology. The number of primary and secondary follicles and cystic follicles was significantly lower (p < 0.001) in all treatment groups as compared to the disease control group.</p>
 <p><strong>Conclusion:</strong> Canagliflozin is effective for the treatment of PCOS and augments the effect of metformin in a rat model.</p>

Fecal lactoferrin early predicts long-term outcomes in ulcerative colitis: A post-hoc analysis of the UNIFI and PURSUIT trials.

Fecal lactoferrin (FL) is associated with disease activity and relapse in ulcerative colitis. However, whether FL could early predict long-term outcomes in ulcerative colitis is poorly understood. This post-hoc analysis included participants who received biologics and had available data of FL concentration at week 4 from the UNIFI and PURSUIT trials (n=1063). Therapeutic outcomes, including clinical remission, endoscopic improvement and remission, and histological improvement and remission, were evaluated at the end of maintenance therapy. The incidence of colectomy was observed from week 0 to maximum week 228 in the PURSUIT trial (n=667). Multivariate logistic and Cox proportional-hazard regression were conducted to evaluate the associations between FL and therapeutic outcomes and colectomy, respectively. A high FL level at week 4 was associated with poor long-term clinical, endoscopic and histologic outcomes. FL >84.5μg/mL predicted a low likelihood of clinical (OR [95% CI]: 0.43 [0.32, 0.57]; p<0.001), endoscopic (OR [95% CI]: 0.40 [0.29, 0.56]; p<0.001), and histological (OR [95% CI]: 0.27 [0.14, 0.53]; p<0.001) remission. Moreover, week-4 FL could add prognostic value to fecal calprotectin and clinical and endoscopic scores for informing long-term therapeutic outcomes. For the risk of colectomy, patients with week-4 FL <20.1 and ≥20.1µg/mL had an incidence rate of 1.10% and 6.39%, respectively. Patients with FL ≥20.1µg/mL had a 995% higher risk of colectomy (HR [95% CI], 10.95 [1.45, 82.74]). FL could be a promising prognostic biomarker for long-term therapeutic outcomes and risk of colectomy in patient of ulcerative colitis.

Exploring the Impact of Nutrition on Non-Alcoholic Fatty Liver Disease Management: Unveiling the Roles of Various Foods, Food Components, and Compounds.

There is a need to introduce standardized treatment options for non-alcoholic fatty liver disease (NAFLD) due to its global prevalence and the complications of this disease. Many studies have revealed that food-derived substances may be beneficial in dealing with this disease. Therefore, this review aims to evaluate the recently published studies on the food-derived treatment options for NAFLD. A comprehensive search of the PubMed database using keywords such as "NAFLD", "nutrition", "food", "derived", "therapy", and "guidelines" yielded 219 relevant papers for our analysis, published from 2004 to 2023. The results show the significant benefits of food-derived treatment in NAFLD therapy, including improvements in liver histology, hepatic fat amounts, anthropometric measures, lipid profile, and other metabolic measures. The availability of the substances discussed makes them a significant adjuvant in the treatment of this disease. The usefulness of Viusid as additional therapy to diet and physical activity should be emphasized due to improvements in liver histology; however, many other substances lead to a decrease in liver fat amounts including, e.g., berberine or omega-3 fatty acids. In addition, the synbiotic Protexin seems to be useful in terms of NAFLD treatment, especially because it is effective in both obese and lean subjects. Based on the latest research results, we suggest revising the therapeutic recommendations for patients suffering from NAFLD.

TOP-091 - Non-invasive tests of liver injury, inflammation and fibrosis are improved by efruxifermin and correlate with histological improvements in F2-F3 NASH patients: secondary analysis of Ph2b HARMONY study

TOP-091 - Non-invasive tests of liver injury, inflammation and fibrosis are improved by efruxifermin and correlate with histological improvements in F2-F3 NASH patients: secondary analysis of Ph2b HARMONY study

Liver histological reversibility of lamivudine in treatment-naïve children with chronic hepatitis B: a retrospective cohort study from a single center Shanghai China.

Low viral load of hepatitis B virus (HBV) infection may also result in serious liver complications. Whether long-term suppression of HBV replication has beneficial effects on the reversibility of the liver histology associated with chronic hepatitis B (CHB) in children is unclear. This study assessed the histological response of lamivudine (LAM) in CHB children. Treatment-naïve CHB patients who 1≤ aged <18 years, indicating the immune-active phase, and receiving LAM were enrolled. Demographics, biochemical value, virology and histology, and safety were retrospectively analysed. Patients visit the hospital at baseline, every 12 weeks during treatment, and every 24 or 48 weeks after treatment withdrawal. Histological inflammatory improvement was defined as a ≥1-point decrease in the inflammatory score. Fibrosis regression was defined as a decrease of ≥1 point or no worsening of the fibrosis score. Total 35 children enrolled, 13 of them were lost, and 22 patients remained in the study up to 10 years after treatment. Liver biopsy results both at baseline and before treatment withdrawal were available for 14 of the 22 patients. Of the 14 children, 78.6% were male and 78.6% were HBeAg-positive. At baseline, the mean age was 7.3±5.2 years. The serum HBV DNA level of 13 subjects was 7.3±1.3 log10 IU/m. and alanine aminotransferase (ALT) was 142±102 U/L. The mean inflammation score was 2.9±0.7. The mean fibrosis score was 3.7±0.8. The mean duration was 96.0±23.6 weeks (median 96 weeks). All patients (100%) had a normal ALT after a median 12-week treatment; after 24-week, HBV DNA were <1,000 IU/mL in 92.9%. At a median of 30-week, 100% of the HBeAg-positive patients showed HBeAg seroconversion; 7.1% exhibited HBsAg seroconversion after 24-week treatment. After a mean of 96-week, the 14 patients (100%) exhibited a mean 2.2-point inflammatory improvement from baseline (P<0.001), and 92.9% exhibited a mean 2.1-point fibrosis reduction (P<0.001). No virological breakthroughs or serious adverse events occurred. This study showed that 96-week mean duration of LAM may reverse advanced inflammation and fibrosis/cirrhosis in young CHB children.

SAT-507 - A biomarker of fibrosis resolution, CTX-III, increases after bariatric surgery in early NAFLD patients with histological liver improvements

SAT-507 - A biomarker of fibrosis resolution, CTX-III, increases after bariatric surgery in early NAFLD patients with histological liver improvements

Toxic effects of synthetic and natural indigo dyes on Danio rerio reproduction

The textile industry releases significant amounts of toxic pollutants. In the aquatic environment, the presence of these compounds can impact fauna and flora. The aim of this study was to verify if synthetic (95% purity) and natural indigo blue dye obtained from Indigofera tinctoria plants pose a risk to the aquatic fauna. To investigate ecotoxicological effects of these dyes at concentration of 100 mg.L-1, adult females and males of Danio rerio were exposed in chronic tests. At the end of the twenty-first day, reproduction was performed to evaluate the endpoints: number of eggs, egg viability, larvae survival, and gonadal histology, and the same experiments were repeated after another 21 days in clean water to evaluate the potential of biological recovery. All of the analyzed reproductive parameters were significantly reduced in the organisms exposed to both synthetic and natural indigo blue dyes in relation to the control, and males exposed to the synthetic dye, and females exposed to both natural and synthetic dyes presented gonadal histological alterations, evidencing an important chronic effect of these substances to the reproduction of D. rerio. After the biological recovery period, organisms exposed to both types of dyes showed histological improvements and they recuperated offspring production, but those exposed to the natural dye showed better reproductive performance. Overall, our findings suggested that levels of natural and synthetic indigo dyes permitted by the current legislations must be reviewed, and the substitution of synthetic by natural indigo whenever possible is recommended.

(011) Beneficial Effects of Vaginal Prasterone (DHEA) on the Vaginal Histology of Women with GSM Beyond the Epithelium

Abstract Introduction There is mounting evidence that androgens play an important role, together with estrogens, in the maintenance of genitourinary health. Objective Vaginal prasterone was used to characterize the histological changes associated with the dual androgen - estrogen stimulation of the vaginal wall in the treatment of the genitourinary syndrome of menopause (GSM). Since prasterone is converted to androgens which are subsequently aromatised in estrogens, a group of patients on aromatase inhibitors (AI) was included to isolate changes attributable to androgens. Methods Vaginal biopsies and vulvar pictures were collected before and after 12 weeks of treatment with 6.5 mg intravaginal prasterone daily (Intrarosa®). Eight women with GSM were recruited, including two breast cancer survivors on AI. Results Following treatment, the epithelium showed striking histological improvements, regaining thickness, ridges, active proliferation and glycogen synthesis. In the lamina propria, treatment led to increases in elastin content and nerve endings density. Visual evaluation of the vulva showed reduction of the redness and inflammation in the vestibule and the urethral meatus as well as a relaxation of the vaginal entrance. All observations were consistent between the groups with and without AI. Conclusions Data presented here are believed to be the first demonstration of the beneficial effects of androgens deep into the lamina propria of GSM patients both together with or independently from estrogens. Tissue changes observed could help understand some of the GSM symptomatology improvements observed before on dyspareunia and other sexual function parameters. While further studies are warranted to better understand how androgens and estrogens work synergistically in the treatment of GSM, the data presented here strongly suggest that prasterone has deep beneficial impacts on the urogenital tissue. Disclosure Yes, this is sponsored by industry/sponsor: Endoceutics Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endoceutics

P17 Platelet-rich plasma as a treatment for vulval lichen sclerosus: a systematic review of safety and efficacy

Abstract Introduction Vulval lichen sclerosus (VLS) is an inflammatory skin disease characterised by pain, itching, burning, apareunia, loss of vulval architecture and scarring. VLS has a significant impact on patients’ quality of life and certain patients find no symptomatic relief in the gold standard treatment of topical corticosteroids. Platelet-rich plasma (PRP) is derived from autologous plasma and injected into disease areas, it may provide superior outcomes for patients than current treatment options. This study systematically reviewed the safety and efficacy of platelet-rich plasma as a treatment for VLS. Methods This review followed PRISMA guidelines using a registered protocol (PROSPERO:CRD42022379894). Multiple databases were searched, along with grey literature on Clinicaltrials.gov, European Union Clinical Trials, and International Standard Randomised Controlled Trial registries. All studies evaluating the safety and/or efficacy of PRP for VLS were included. Results A total of 213 patients were assessed across nine studies. There was significant heterogeneity between studies, in the study design, PRP preparation method and injection volume of plasma used, and outcome measures. Forty-one percent (n=88) of patients reported resolution of symptoms on Quality-of-Life outcome measures or symptom assessment scales, 6% (n=12) patients had histological improvement of inflammation. PRP demonstrated symptom resolution and improvement, however the evidence is insufficient to conclude on its effectiveness or safety, and heterogenous outcome measures preclude pooled data analysis. Conclusion PRP may provide superior results than corticosteroids in certain patients with VLS, however further research is needed to ascertain the safety and efficacy profile of this treatment.

Histological improvement in chronic hepatitis C-autoimmune hepatitis overlap syndrome by glecaprevir and pibrentasvir.

A 60-year-old man with type-2 diabetes and chronic hepatitis C (HCV) was diagnosed with single hepatocellular carcinoma (HCC) of 67mm in the hepatic posterior right lobe. Lenvatinib 8mg was initiated but discontinued because of grade 3 liver injury. The patient continued to have prolonged liver injury and persistently high immunoglobulin G levels. Antinuclear antibody titer increased from 1:40 to 1:320. Histopathological examination of a liver biopsy specimen revealed interface hepatitis with lymphocyte and plasma cell infiltration, rosette formation, and emperipolesis, suggesting the possibility of autoimmune hepatitis (AIH). First, treatment with prednisolone was initiated; however, the response was poor. After starting glecaprevir/pibrentasvir (GLE/PIB) as direct-acting antivirals (DAA), HCV RNA rapidly disappeared, and serological liver function improved. After confirmation of sustained virological response 24, HCC recurrence was observed, and partial hepatectomy was performed. Background liver findings showed that liver parenchymal inflammation improved compared with that before DAA treatment. This is the first case of HCV-AIH overlap syndrome treated with DAA using GLE/PIB. Liver function improved within a short treatment period of 8weeks, as confirmed using serology and histology.

Neuroprotective effect by naringin against fluorosis-induced neurodegeneration in adult Wistar rats.

Fluorosis is widespread in several areas of the world and including India leading to dental and skeletal fluorosis as well as neurological manifestations. With a limited number of treatment options available, we have tried to address the issue with a nutraceutical such as naringin which is an alkaloid derived from the citrus fruit. Naringin is a potent antioxidant and has neuroprotective action which can counteract the redox imbalance induced by sodium fluoride ingestion. Neurological effects of fluorosis were evaluated in Wistar rats by open field test (OFT) and novel object recognition test (NORT) along with lipid peroxidation (LPO) and glutathione estimation in brain homogenate and cresyl violet staining of CA3 neurons in the hippocampus. Animals were divided into groups namely, normal, vehicle, fluoride, naringin 100 mg/kg bd.wt group and fluoride with naringin (FLU-NAR) group. Fluorosis was induced by providing 100 ppm of sodium fluoride ad libitum in drinking water for 30 days and prophylactic treatment of naringin for 15 days per oral. OFT, NORT and forced swim test showed significant (P ≤ 0.05) changes in the FLU-NAR group as compared to the fluoride group indicating behavioral changes in the fluoride group and positive changes in the FLU-NAR group with attenuation of stress, fear, hyperactivity and memory impairment. The decrease in LPO and increase in glutathione levels in the treatment group compared to the fluoride group were supported by histological improvement as compared to the fluoride group. Prophylactic treatment of naringin showed its possible neuroprotective effect, thus giving an alternative treatment strategy to deal with neurological manifestations of fluorosis.

CeAF Ameliorates Diabetic Wound Healing by Alleviating Inflammation and Oxidative Stress via TLR4/NF-κB and Nrf2 Pathways.

With the rise in diabetes incidence, diabetic foot ulcers have become the most common clinically chronic refractory wounds. Persistent chronic inflammation is a typical feature of diabetic cutaneous wounds, and diabetic wound healing can be improved by alleviating inflammation and oxidative stress. Chick early amniotic fluids (ceAF) consist of native conglutinant substances with balanced amounts of growth factors, cytokines, and chemokines. However, whether ceAF modulates inflammation and oxidative stress and thus promotes diabetic wound healing remains unknown. RAW264.7 cells were categorized into four groups: negative control, LPS, LPS + ceAF, and ceAF. 10% of ceAF was selected to treat different groups of mice with a full-thickness skin defect wound. Then, RT-qPCR, western blot, immunofluorescence, and other assays were carried out to explore the effect of ceAF on wound healing and its molecular mechanism. Topical administration of ceAF improved M2 macrophage polarization and inflammatory response in the wound tissues, thereby ameliorating delayed wound healing. Histological improvement could be observed in the grade of inflammation, collagen deposition, and neovascularization in wound edge tissues. ceAF also increased M2 macrophage-specific markers expression and exogenous ceAF suppressed LPS-induced cellular inflammatory response in vitro high glucose environment. Additionally, ceAF could activate TLR4/NF-κB and Nrf2 signal transductions to promote M2 macrophage polarization in vitro. In summary, ceAF downregulates inflammatory response, regulates M2 macrophage transition via TLR4/NF-κB and Nrf2 signaling pathways, and thus improves diabetic wound healing.

Histopathological response to denosumab in giant cell tumours of bone - A review of 11 cases.

Giant cell tumor (GCT) of the bone is a locally aggressive primary bone tumor, that can rarely metastasize. Arising mostly in epiphysis of the long bones in young adults, the tumor is composed of mononuclear cells that are admixed with osteoclastic giant cells(OLGCs), which express RANK ligand and RANK respectively. Denosumab a monoclonal antibody against RANK ligand has been shown to reduce the tumor by causing bone lysis by inhibiting RANKL. Histological changes in 11 patients of GCT who were treated with denosumab are presented here. Clinical records and slides of 11 patients of GCT who had been administered neoadjuvant denosumab were included in the study. Evaluation of pre and post therapy GCT specimens was performed by two pathologists (RK and VM). There were 4 males and 7 females. Their mean age was 30 years. All the patients received 120 mg denosumab subcutaneously every week with additional 120 mg on days 8 and 15 of therapy. The histological slides were reviewed and following points noted: 1) degree of ossification,2) fibrosis,3) loss of osteoclastic giant cells,4) proliferation of mononuclear cells,5) atypia,6) Permeation of osteoid by malignant cells. Out of 11 cases, 2 cases did not show any significant histological improvement. 7 cases showed reduction in giant cells, increased fibrosis, enhanced mononuclear cell proliferation and ossification consistent with a pathological response. Atypia and osteoid permeation were noted in 2 cases which showed transformation to osteosarcoma. Denosumab treated giant cell tumor show dramatic histological changes. The post therapy lesions may bear no resemblance to pretherapy lesion. There may be complete resolution or may be confused with benign or malignant lesions Rarely they may show sarcomatous transformation. It is imperative that the pathologist is aware of these changes to prevent diagnostic pitfalls as it poses therapeutic and prognostic implications.

MACHINE LEARNING-BASED PREDICTION OF GEBOES SCORE AND HISTOLOGIC IMPROVEMENT AND REMISSION THRESHOLDS IN ULCERATIVE COLITIS

Histology is emerging as a key therapeutic endpoint for ulcerative colitis driven by associations between histologic response and long-term outcomes. However, existing scoring systems are subjective and consequently have variable inter- and intra-reader variability. Geboes scoring is a well-established system for ulcerative colitis histologic assessment that has previously been used to define thresholds for histo-endoscopic mucosal improvement (Geboes Score ≤3.1, together with Mayo score 0 or 1) and histologic remission (Geboes Score <2). Here we report the first machine learning (ML)-based prediction of the Geboes Score, and Geboes Score-derived thresholds of histologic improvement and remission, directly from whole slide images (WSI) of hematoxylin and eosin (H&E)-stained mucosal biopsies.

A comparative study of acetyl-l-carnitine and caloric restriction impact on hippocampal autophagy, apoptosis, neurogenesis, and astroglial function in AlCl3-induced Alzheimer's in rats.

Alzheimer's disease (AD) is a worldwide chronic progressive neurodegenerative disease. We aimed to investigate and compare the neuroprotective impact of acetyl-l-carnitine and caloric restriction (CR) on AlCl3-induced AD to explore the pathogenesis and therapeutic strategies of AD. Sixty-seven adult male Wistar rats were allocated into Control, AlCl3, AlCl3-acetyl-l-carnitine, and AlCl3-CR groups. Each of AlCl3 and acetyl-l-carnitine were given by gavage in a daily dose of 100mg/kg and CR was conducted by giving 70% of the daily average caloric intake of the control group. Rats were subjected to behavioral assessment using open field test, Y maze, novel object recognition test and passive avoidance test, biochemical assay of serum phosphorylated tau (pTau), hippocampal homogenate phosphorylated adenosine monophosphate-activated protein kinase, Beclin-1, Bcl-2-associated X protein, and B cell lymphoma 2 (Bcl2) as well as hippocampal Ki-67 and glial fibrillary acidic protein immunohistochemistry. AlCl3-induced cognitive and behavioral deficits coincident with impaired autophagy and enhanced apoptosis associated with defective neurogenesis and defective astrocyte activation. Acetyl-l-carnitine and CR partially protect against AlCl3-induced behavioral, cognitive, biochemical, and histological changes, with more ameliorative effect of acetyl-l-carnitine on hippocampal apoptotic markers, and more obvious behavioral and histological improvement with CR.

VEGFA-modified DPSCs combined with LC-YE-PLGA NGCs promote facial nerve injury repair in rats

ObjectiveThe aim of this research was to investigate the effect of vascular endothelial growth factor A (VEGFA)-overexpressing rat dental pulp stem cells (rDPSCs) combined with laminin-coated and yarn-encapsulated poly(l-lactide-co-glycolide) (PLGA) nerve guidance conduit (LC-YE-PLGA NGC) in repairing 10 mm facial nerve injury in rats. Study DesignrDPSCs isolated from rat mandibular central incisor were cultured and identified in vitro and further transfected with the lentiviral vectors (Lv-VEGFA). To investigate the role and mechanisms of VEGFA in neurogenic differentiation in vitro, semaxanib (SU5416), Cell Counting Kit-8 (CCK-8), real-time quantitative polymerase chain reaction (qPCR) and Western blotting were performed. Ten-millimeter facial nerve defect models in rats were established and bridged by LC-YE-PLGA NGCs. The repair effects were detected by transmission electron microscopy (TEM), compound muscle action potential (CMAP), immunohistochemistry and immunofluorescence. ResultsExtracted cells exhibited spindle-shaped morphology, presented typical markers (CD44+CD90+CD34−CD45−), and presented multidirectional differentiation potential. The DPSCs with VEGFA overexpression were constructed successfully. VEGFA enhanced the proliferation and neural differentiation ability of rDPSCs, and the expression of neuron-specific enolase (NSE) and βIII-tubulin was increased. However, these trends were reversed with the addition of SU5416. This suggests that VEGFA mediates the above effects mainly through vascular endothelial growth factor receptor 2 (VEGFR2) binding. The LC-YE-NGC basically meet the requirements of facial nerve repair. For the in vivo experiment, the CMAP latency period was shorter in DPSCS-VEGFA-NGC group in comparison with other experimental groups, while the amplitude was increased. Such functional recovery correlated well with an increase in histological improvement. Further study suggested that VEGFA-modified DPSCs could increase the myelin number, thickness and axon diameter of facial nerve. NSE, βIII-tubulin and S100 fluorescence intensity and immunohistochemical staining intensity were significantly enhanced. ConclusionVEGFA-modified rDPSCs combined with LC-YE-PLGA NGCs have certain advantages in the growth and functional recovery of facial nerves in rats.

Gene therapy for cross-correction of somatic organs and the CNS in mucopolysaccharidosis II in rodents and non-human primates

Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by deficient activity of iduronate-2-sulfatase (I2S), leading to pathological accumulation of glycosaminoglycans (GAGs) in tissues. We used iduronate-2-sulfatase knockout (Ids KO) mice to investigate if liver-directed recombinant adeno-associated virus vectors (rAAV8-LSP-hIDSco) encoding human I2S (hI2S) could cross-correct I2S deficiency in Ids KO mouse tissues, and we then assessed the translation of mouse data to non-human primates (NHPs). Treated mice showed sustained hepatic hI2S production, accompanied by normalized GAG levels in somatic tissues (including critical tissues such as heart and lung), indicating systemic cross-correction from liver-secreted hI2S. Brain GAG levels in Ids KO mice were lowered but not normalized; higher doses were required to see improvements in brain histology and neurobehavioral testing. rAAV8-LSP-hIDSco administration in NHPs resulted in sustained hepatic hI2S production and therapeutic hI2S levels in cross-corrected somatic tissues but no hI2S exposure in the central nervous system, perhaps owing to lower levels of liver transduction in NHPs than in mice. Overall, we demonstrate the ability of rAAV8-LSP-hIDSco to cross-correct I2S deficiency in mouse somatic tissues and highlight the importance of showing translatability of gene therapy data from rodents to NHPs, which is critical for supporting translation to clinical development.

European multicenter study on the real-world use and clinical impact of extracorporeal photopheresis after heart transplantation

Aim of this study was to describe the real-world use of extracorporeal photopheresis (ECP) and assess its impact on clinical outcomes in the modern era of heart transplantation. Seven transplant centers from 5 European countries participated in this retrospective, observational, single-arm chart review study. All patients received ECP after heart transplantation in 2015 or later. Data were extracted from medical records between November 2020 and December 2021. Overall, 105 patients were enrolled and followed for an average of 2 years after initiation of ECP. Reasons to start ECP were acute cellular rejection (35.2%), rejection prevention (32.4%), mixed rejection (18.1%), and antibody-mediated rejection (14.3%). Rejection ISHLT grades improved from start to end of ECP treatment in 92% of patients treated with ECP for rejection. Of patients who started ECP to prevent rejection, 88% remained free from any rejection despite a reduction of calcineurin inhibitors. Overall survival was 95%, and no deaths were related to ECP. Safety events occurred in 18 patients, of which 13 experienced complications with venous access. This study, the largest European ECP study in heart transplantation, demonstrates that ECP can effectively be used to treat different rejection types and to prevent rejection in the modern era of immunosuppression. Patients with rejections who have received ECP have shown high response as measured by histological improvements in ISHLT classification. A high percentage of patients in the prevention group remained free from rejection despite reduction in immunosuppression, in particular calcineurin inhibitors.

Clinical utility of urinary gluten immunogenic peptides in the follow-up of patients with coeliac disease.

Gluten-free diet (GFD) is the only treatment for patients with coeliac disease (CD) and its compliance should be monitored to avoid cumulative damage. To analyse gluten exposures of coeliac patients on GFD for at least 24 months using different monitoring tools and its impact on duodenal histology at 12-month follow-up and evaluate the interval of determination of urinary gluten immunogenic peptides (u-GIP) for the monitoring of GFD adherence. Ninety-four patients with CD on a GFD for at least 24 months were prospectively included. Symptoms, serology, CDAT questionnaire, and u-GIP (three samples/visit) were analysed at inclusion, 3, 6, and 12 months. Duodenal biopsy was performed at inclusion and 12 months. At inclusion, 25.8% presented duodenal mucosal damage; at 12 months, this percentage reduced by half. This histological improvement was indicated by a reduction in u-GIP but did not correlate with the remaining tools. The determination of u-GIP detected a higher number of transgressions than serology, regardless of histological evolution type. The presence of >4 u-GIP-positive samples out of 12 collected during 12 months predicted histological lesion with a specificity of 93%. Most patients (94%) with negative u-GIP in ≥2 follow-up visits showed the absence of histological lesions (p < 0.05). This study suggests that the frequency of recurrent gluten exposures, according to serial determination of u-GIP, could be related to the persistence of villous atrophy and that a more regular follow-up every 6months, instead of annually, provides more useful data about the adequate adherence to GFD and mucosal healing.

A235 “WHAT’S SPRUE WITH YOU?”: OLMESARTAN-INDUCED ENTEROPATHY AS AN UNCOMMON MIMICKER OF CELIAC DISEASE

Abstract Background Olmesartan-induced enteropathy is an uncommon mimicker of celiac disease. Symptoms include diarrhea and weight loss and pathology shows villous atrophy, intraepithelial lymphocytes, and subepithelial collagen deposition. In contrast to celiac disease, tissue transglutaminase (TTG) is not elevated and gluten avoidance does not induce clinical or histologic improvement. Both clinical and histologic findings are reversible with cessation of pharmacologic therapy. Purpose To raise clinician awareness of an uncommon but reversible cause of enteropathy. Method A 67-year old man presented with 3 months of progressive diarrhea and 35lb weight loss on a background of hypertension, dyslipidemia, and type 2 diabetes. His medications included olmesartan, amlodipine, metformin, aspirin, and atorvastatin, none of which were new. Infectious stool studies, serum and fecal inflammatory markers, imaging, TTG and IgA were normal. Panendoscopy revealed duodenitis with biopsies consistent with active enteritis, intraepithelial lymphocytosis and villous shortening suggestive of olmesartan-induced enteropathy given negative TTG. Olmesartan was discontinued. Result(s) His symptoms completely resolved over several weeks after discontinuation. Conclusion(s) Olmesartan is an uncommon but reversible mimicker of celiac disease. It was first described in 2012 in a case series of 22 patients, all of whom had negative celiac serology and demonstrated histologic and clinical improvement with cessation of olmesartan. Time from medication initiation to onset of symptoms ranged from 6 months to 7 years, with a mean of 3.1 years. While case reports exist of angiotensin-receptor blockers as causative agents, the most common is olmesartan, implicated in 94% of ARB-induced enteropathy cases in a recent systematic review. The exact mechanism of injury is unknown. The delay in onset of symptoms suggests a cell-mediated immunity phenomenon. An immune-mediated reaction is also supported by the high prevalence of HLA-DQ2/DQ8 haplotypes (71%) among affected individuals vs. 30-40% in the general population. Olmesartan may be implicated more strongly than other ARBs due to its higher affinity for AT1 receptors; theoretically leaving unsaturated AT2 receptors to bind angiotensin. AT2 receptors are known to induce cellular apoptosis, and unopposed cellular death could theoretically lead to villous atrophy. The overall risk of developing enteropathy on olmesartan is rare, but not well quantified. This is likely due to both underrecognition, and variability in study designs leading to inability to perform meta-analysis on currently available data. Data from a French cohort estimates a crude incidence rate of 5.6 per 100,000 person years for patients on olmesartan developing intestinal malabsorption requiring hospitalization. Despite its rarity, prescribers should be cognizant of this side effect which can evolve even after years of medical therapy. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared