Pracovní skupina pro idiopatické střevní záněty (PS IBD) České gastroenterologické společnosti přináší v následujícím textu aktualizovaná doporučení pro medikamentózní léčbu ulcerózní kolitidy (UC). Tato doporučení zahrnují přehled léků konvenčních i medikamentů označovaných jako pokročilá (advanced) nebo též cílená léčba. Její rychlý rozvoj v posledních letech dále akceleroval a přinesl nové možnosti pacientům, u nichž konvenční léčiva selhávají nebo nejsou tolerována. Aktualizovaná doporučení jsou ve srovnání s předchozími [1] textem stručnějším a více zaměřeným na praktické informace o léčbě. Užitečnou pomůckou by pro čtenáře měl být závěrečný algoritmus, který shrnuje současné poznatky a zkušenosti expertů PS IBD v oblasti cílené terapie UC. Praktickou stránku textu podtrhuje i rozdělení cílené léčby na léky první linie a vyšších linií tak, jak stanovují aktuální úhradové podmínky Státního ústavu pro kontrolu léčiv (SÚKL). Do textu jsme nezařadili část věnovanou léčbě IBD v graviditě a laktaci, toto téma bude publikováno v samostatném článku v některém z dalších čísel časopisu. Narůstající potřeba moderní léčby spolu s dramaticky stoupajícími počty pacientů s UC v České republice vyžadují zapojení stále většího počtu aktivních gastroenterologů a zájemců o problematiku IBD. Právě jim je následující text určen především.

Inflammatory bowel diseases (IBD) and primary sclerosing cholangitis (PSC) are chronic inflammatory conditions with limited biomarker-driven diagnostic tools. Proteomic profiling offers a promising approach to uncover specific biomarkers that could refine diagnostic accuracy, monitor disease activity, and guide therapeutic strategies. Our primary aim is to identify novel biomarkers for PSC-IBD and conventional ulcerative colitis (UC) via proteomic approach. The secondary aim is to advance the etiopathogenic understanding of the diseases by linking specific proteomic profiles with disease phenotypes. This single-center, prospective, biomarker-discovery study will involve 50 participants with PSC-IBD, 50 with UC, and 50 healthy controls. Biopsy samples from five bowel segments will be analyzed for proteomic signatures by an untargeted approach. The findings will subsequently undergo multi-step external validation in separate cohorts of 30 patients with PSC-IBD and 30 with UC, utilizing targeted proteomics, immunohistochemistry, and ELISA in bowel mucosa and peripheral blood, respectively. This proposed study aims to identify novel biomarkers to improve the diagnostic accuracy of PSC-IBD and UC and refine the disease activity assessment. Its robust design and large sample size provide a strong foundation for successful biomarker identification, with the potential to enhance clinical management of patients.

Patients with primary sclerosing cholangitis (PSC) often undergo orthotopic liver transplantation (OLTx) for end-stage disease. PSC is closely associated with inflammatory bowel disease (IBD), and some patients experience refractory course after OLTx. Upadacitinib (UPA) is a novel, effective, orally administered, selective JAK1 inhibitor introduced for the treatment of ulcerative colitis with limited data on post-OLTx population. This study aims to evaluate efficacy and safety of UPA on post-OLTx PSC patients with IBD. This retrospective, single-centre observational study was conducted at IKEM, Czech Republic. We included all patients with PSC who underwent OLTx and had concomitant IBD, who were started on UPA and followed at our centre. The induction dose of UPA was 45 mg daily for three months for all patients, followed by a maintenance dose of 15–45 mg daily. The partial Mayo score (pMayo) and Mayo endoscopic subscore (MES) were used to evaluate IBD activity at baseline and the end of follow-up. Prednisolone (5–40 mg) was administered to all patients except one, who received budesonide (9 mg) daily. Data were extracted from patients’ medical records and charts and stored in MS Excel. Prism 10 was used for statistical analysis; the Wilcoxon rank test was used to compare pMayo and MES before and after treatment. In total, 10 patients were included, with a median follow-up of 13.3 months (range 1.6–21.9). Baseline cohort characteristics are shown in Table 1. There was a significant decrease in the median pMayo score from 5.5 at baseline to 2 at the end of follow-up (p < 0.01, Figure 1A). Clinical response was observed in all patients except one, who had no initial response. Follow-up endoscopy was performed in 7 patients. The median MES decreased from 3 at baseline to 0 or 1 in three patients, and from 2 to 1 in the other three patients at follow-up endoscopy, but this change did not reach statistical significance (p = 0.625, Figure 1B). Endoscopic remission was confirmed in two patients. Half of the included patients experienced mild adverse effects: acne, rash, recurrent upper respiratory tract infections, CMV colitis, and mild Covid-19 infection. No serious adverse events were detected. There were no changes in liver enzymes or tacrolimus levels during follow-up compared with baseline. Two of the seven patients with re-PSC showed a tendency for decreased ALP and GGT levels; the other patients had stable liver test results. UPA was discontinued in two patients, one due to adverse events and the other due to primary failure. UPA appears to be an effective and safe treatment option for active IBD after OLTx and failure of previous biologic or innovative therapy. Conflict of interest: Dr. Hlavaty, Mojmir: No conflict of interest Brezina, Jan: No conflict of interest Bajer, Lukas: No conflict of interest Trunecka, Pavel: No conflict of interest Hucl, Tomas: No conflict of interest Drastich, Pavel: No conflict of interest

Celiac disease is a systemic autoimmune affliction triggered by dietary gluten in genetically predisposed subjects. Current estimation of the prevalence of celiac disease is approximately 1% for the global population. These data are consistent with current figures from the Czech Republic (prevalence of 1.06% in 2023). Celiac disease can be associated with several complications including malignancy. Exact epidemiology data on T-cell lymphoma and small intestinal adenocarcinoma in the Czech Republic over the period 2010–2023 are also provided. Unlike the no-biopsy approach in children, despite current non-conclusive discussion and besides serology, upper gastrointestinal endoscopy, biopsies, and histology are mandatory for proper diagnosis and initial assessment of the severity of celiac disease in adults. However, there are so far no unified and integrated recommendations for the follow-up of adult celiac disease. Although the risk of malignancy in celiac disease is relatively low, especially in a strict gluten-free diet, it might nevertheless be further decreased by an individualized surveillance. Endoscopy controls with biopsies for histology, immunohistochemistry, and flow cytometry are essential. The purpose of this article was to review the risk and diagnostics of malignancy in celiac disease. A proposal for the individualized surveillance of premalignant gastrointestinal lesions in adult celiac disease was drafted.

Background: The expanding therapeutic landscape of ulcerative colitis (UC) introduces uncertainty regarding the optimal positioning of new agents. Objectives: This study aimed to compare the real-world persistence of advanced therapies for UC. Design: This observational cohort study used a population-based national registry of biologic and small-molecule therapies for inflammatory bowel disease, CREdIT, to identify patients treated with advanced therapy for UC. Methods: The primary outcome was treatment persistence – defined as time from therapy initiation to discontinuation or last follow-up, whichever occurred first – and was analysed using mixed-effects Cox models and inverse probability weighting. Persistence was assessed overall, in first-line therapy, and in second-line therapy after adalimumab or infliximab exposure. Results: We included 3718 observations from 2525 patients with UC (48% female). Infliximab (40%), vedolizumab (27%) and adalimumab (17%) were most frequently used. At 5 years, 1852 of 3718 observations (49.8%) remained on the same therapy. The treatment line alone was not associated with treatment persistence after accounting for patient-level clustering using a mixed-effects model. Vedolizumab showed significantly greater persistence than infliximab or adalimumab, including in first-line use. In second-line settings post-anti-tumour necrosis factor (TNF) exposure, upadacitinib had the highest persistence compared to tofacitinib, vedolizumab and ustekinumab, whereas vedolizumab was more persistent than tofacitinib. Conclusion: Vedolizumab demonstrated longer persistence than infliximab or adalimumab, regardless of treatment line. Following anti-TNF failure, upadacitinib showed the highest persistence.

The impairment of intestinal barrier function is implicated in primary sclerosing cholangitis, but the clinical evidence is scarce. Therefore, we performed a cross-sectional study to evaluate serological markers of inflammation and intestinal permeability (Reg3a, iFABP, Zonulin, Calprotectin) in patients after liver transplantation (LT) for PSC. The cohort included 26 subjects with PSC recurrence (rPSC), 87 subjects without PSC recurrence (non-rPSC), and a unique control group consisting of post-LT patients (n = 113) transplanted due to alcohol cirrhosis. Generalized Linear Models were calculated to assess the association between serological markers of intestinal barrier function or inflammation (IP_Models) and PSC diagnosis per se (IP_Model_1), non-rPSC (IP_Model_2) or rPSC incidence (IP_Model_3) and compared with models (ST_Models) based on validated PSC markers (ALP, GGT, bilirubin). The increased probability of PSC occurrence (IP_Model_1, p < 0.001, AIC = 182) was associated with higher serum Reg3a concentration, while a negative association was found for iFABP, BMI, and age. The probability of non-recurrence (IP_Model_2, p < 0.001, AIC = 167) was associated with lower Reg3a concentration, older age, and BMI. The performance of IP_Models_1,2 and ST_models_1,2 was comparable. rPSC prediction was less precise by both models (IP_Model_3 p = 0.063, AIC = 92; ST_Model_3 p < 0.001, AIC = 108). rPSC incidence was positively associated with fecal calprotectin and serum zonulin concentrations, while it was independent of Reg3a, iFABP, age or BMI. In conclusion, this pilot study suggests that impaired intestinal permeability is associated with the pathophysiology of rPSC. Our data could serve as a basis for testing in a larger independent validation cohort and, if confirmed, help to explain the mechanisms underlying the pathophysiology of PSC and the recurrence of this disease after transplantation.

BACKGROUND & AIMS:Primary sclerosing cholangitis (PSC)-associated alterations of fecal gut microbiota have already been described, but data on the mucosal microbiota are still limited. We aimed to further define disease-specific mucosal microbial patterns independent of geography and assess the relationship to liver transplantation (LTx), gut inflammation (inflammatory bowel disease), and PSC recurrence (rPSC). METHODS:We performed 16S ribosomal RNA gene (V3-V4) sequencing of ileocolonic biopsies from 115 patients with PSC (pre-LTx), 159 liver-transplanted patients (post_LTx, recurrence occurred in 38), and 96 healthy controls (HC) from Norway and the Czech Republic. RESULTS:Alpha diversity was lower in all PSC groups compared with HC. Elastic net models discriminated pre_LTx (AUC ileum 0.97; colon 0.93; p <0.001) and post_LTx PSC patients (AUC ileum 0.97; colon 0.97; p <0.001) from HC, and distinguished pre_LTx from post_LTx (AUC ileum 0.83; colon 0.83; p <0.001). The shared, cohort-independent PSC microbiota was dominated by Enterococcus, Pseudomonas, Veillonella, Klebsiella, and Streptococcus, while several common commensals were underrepresented. A microbial dysbiosis index calculated from PSC-associated genera correlated negatively with alpha diversity and serum albumin, while a positive correlation was observed with markers of cholestatic disease (ALP, GGT) and liver fibrosis (APRI). There were no associations with the presence of inflammatory bowel disease or fecal calprotectin. Differences between post-LTx patients with and without recurrence were limited, but several genera deregulated in pre-LTx PSC (Klebsiella, Bilophila, Coprococcus, Odoribacter) showed similar trends in rPSC. CONCLUSIONS:Our findings in two European countries revealed a distinct mucosal microbiota composition associated with PSC that persists after LTx. These microbial patterns correlate with the severity of liver injury in PSC but not with markers of intestinal inflammation. IMPACT AND IMPLICATIONS:This study provides an extensive evaluation of mucosa-associated microbiota in primary sclerosing cholangitis (PSC) before and after liver transplantation across two European cohorts. The persistence of PSC-related dysbiosis after transplantation highlights the importance of the gut-liver axis in PSC and supports further investigation into microbiota-driven mechanisms. Together with the strong association between microbiota composition and markers of cholestasis and fibrosis, this suggests potential clinical utility as an indicator of disease activity or even as a target for prevention or therapy.

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease associated with inflammatory bowel disease. Liver transplantation (LT) is the only curative treatment for most patients with PSC. Recurrence of PSC (rPSC) is a common long-term complication after liver transplantation in this patient group, affecting graft survival and overall patient survival. There are several lines of evidence indicating that dysregulation of the microbiome and gut barrier dysfunction are key etiologic factors in the pathogenesis of PSC. The aim of this study was to evaluate serological markers of intestinal barrier function in patients with PSC after LT and in control group, to determine potential biomarkers for rPSC. Methods This is a cross-sectional study of patients after LT for PSC at the Institute for Clinical and Experimental Medicine, Prague. The control group consists of patients who underwent liver transplantation for alcohol-related liver disease and/or hepatocellular carcinoma. The rPSC was assessed by MRCP and/or liver biopsy according to the Mayo criteria. IBD status was assessed by endoscopy, biopsy, and faecal calprotectin. We performed ELISA for Zonulin and Reg3a. The Kruskal-Wallis and Mann-Whitney test were used to evaluate the statistical differences. Results A total of 85 patients were included in the study after LT for PSC and 56 controls. rPSC was detected in 18 (21.18%) patients. IBD was diagnosed in 77 (90.5%) patients, of which 3 (3.9%) were categorised as Crohn’s disease. The remainder, 82 patients, were classified as ulcerative colitis, 41.9% with right-sided predominance and 24.3% with back-wash ileitis. The IBD treatment consisted of 5-ASA in 58 patients, azathioprine in 12 patients, vedolizumab in 5 patients, anti-TNFa in 1 patient and 9 patients were on 10 mg or more of prednisone or equivalent. MayoDAI was evaluated at the time of the visit with mean 1.74 (SD ±2.06). There was a significant difference in Reg3a levels between patients with IBD and control subjects (p<0.05, Figure 1.). No significant difference in Reg3a levels was found between rPSC patients and controls (p=0.3). Interestingly, Zonulin levels were significantly higher in the control group than in PSC patients with or without IBD (p<0.001). No significant difference in Reg3a and Zonulin was found between PSC and rPSC patients and between patients in remission and with active IBD. Conclusion Reg3a was associated with PSC-IBD in patients with PSC after LT, but its association with rPSC is unclear and should be investigated in a prospective setting. Zonulin reached higher levels in the control group.

BACKGROUND Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear. AIM To assess the accuracy of MES in UC and PSC-UC patients, we performed histological scoring using Nancy histological index (NHI). METHODS MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy. NHI and inflammation were evaluated in biopsies from the cecum, rectum, and terminal ileum. In addition, perinuclear anti-neutrophil cytoplasmic antibodies, fecal calprotectin, body mass index, and other relevant clinical characteristics were collected. RESULTS The median MES and NHI were similar for UC patients (MES grade 2 and NHI grade 2 in the rectum) but were different for PSC-UC patients (MES grade 0 and NHI grade 2 in the cecum). There was a correlation between MES and NHI for UC patients (Spearman's r = 0.40, P = 0.029) but not for PSC-UC patients. Histopathological examination revealed persistent microscopic inflammation in 88% of PSC-UC patients with MES grade 0 (46% of all PSC-UC patients). Moreover, MES overestimated the severity of active inflammation in an additional 11% of PSC-UC patients. CONCLUSION MES insufficiently identifies microscopic inflammation in PSC-UC. This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.

Summary: Cholestatic liver diseases are characterized by their progressive nature and limited conservative treatment options. Liver transplantation is the only effective method of treatment for the terminal stage. Before the era of liver transplantation, patients with cholestatic disease had a significantly reduced life expectancy. Liver transplantation is now indicated not only for patients with chronic liver failure or hepatobiliary malignancy, but also for those with reduced quality of life from cholestatic symptoms. Post-transplant care is particularly specific because of the presence of immune-associated diseases, such as inflammatory bowel disease in patients with primary sclerosing cholangitis. Recurrence of the underlying disease in the liver graft is a common long-term complication that can negatively affect graft survival and overall life expectancy. Despite the risk of recurrence, the long-term outcomes of liver transplantation for cholestatic disease are excellent, achieving longer survival compared to other transplant recipients. Key words: liver transplantation – primary sclerosing cholangitis – primary biliary cholangitis – secondary sclerosing cholangitis – liver sarcoidosis

BACKGROUND AND AIMS:Gastric restriction techniques have recently emerged as minimally invasive bariatric procedures. Endoscopic sutured gastroplasty (ESG) with the Endomina (Endo Tools Therapeutics, Gosselies, Belgium) triangulation platform proved to be safe and effective for the treatment of class I and II obesity in prospective studies. In this registry, we aimed to further assess on a larger scale the safety and efficacy of the procedure in routine practice with a dedicated device. METHODS:This was a multicenter, observational, prospective post-market study including patients with obesity undergoing Endomina ESG. The primary safety outcome was the occurrence of serious adverse device effects (SADEs) at 12 months. The primary efficacy outcome was the technical success defined by completing the procedure without premature abortion owing to technical issues. The rates of procedure-related adverse events, weight loss outcomes, and quality of life changes were collected. RESULTS:A total of 142 patients underwent ESG in 3 centers from July 2020 to March 2023. Of these, 67 (mean body mass index, 38.5 ± 6.3 kg/m2) reached at least 12 months of follow-up up to October 2022. Technical success was 100%. No SADEs occurred. Seven mild procedure-related adverse events were reported overall. Mean percentage of excess weight loss and total body weight loss at 12 months' follow-up were 48.5% ± 38.6 and 15.3% ± 10.6, respectively (n = 67). Improved quality of life was observed following ESG. CONCLUSIONS:ESG is safe and effective, thus offering a satisfactory therapeutic option for a wide range of obese patients on a large scale.

Gastrointestinal tract is the most common locality for well-differentiated neuroendocrine tumors (NET). While their occurrence in patients with ulcerative colitis (UC) is uncommon, it has been well documented. However, the causal relationship between development of NET and chronic intestinal inflammation or dysplasia remains controversial. The presence of NET in the ileal pouch in UC patients has been described only in a few reports to date. In this article, we present a case of such a tumor arising in the pouch in a patient with primary sclerosing cholangitis-associated UC, who underwent a restorative proctocolectomy with ileal pouch anal anastomosis and liver transplantation. The case is supported by a review of a relevant literature.   Correspondence address: Ondrej Fabian Clinical and Transplant Pathology Centre Institute for Clinical and Experimental Medicine Videnska 1958/9 Prague, 14021 Czech Republic ondrej.fabian@ikem.cz; ondrejfabian5@gmail.com.

A 59-year-old patient with type 2 diabetes, dyslipidemia, and hypertension underwent the placement of a duodenojejunal bypass (EndoBarrier; GI Dynamics, Boston, Massachusetts, USA). At the time of the endoscopy procedure, the patient weighed 110 kg and was 172 cm tall, resulting in a body mass index (BMI) of 37.3 kg/m2. The procedure, performed under general anesthesia, concluded without complications. Postoperatively, the patient was prescribed 40 mg of proton pump inhibitors (PPIs) twice daily and advised to avoid fiber. Early side effects included daily nausea (five to eight episodes), and epigastric pain was managed with antiemetics and ongoing PPI use. One month later, an endoscopy confirmed the duodenojejunal bypass was correctly positioned but revealed ulcers at the device's sharp edges. Despite initial challenges, symptoms improved significantly within three weeks. After 12 months, the patient had lost 30 kg, reducing their (BMI) to 27.3 kg/m2. The patient chose to keep the bypass despite the conclusion of the study and against medical advice about potential risks.

Background/Aims: Upper gastrointestinal bleeding (UGIB) is the most common GI condition requiring hospitalization. The present study aimed to evaluate the safety and feasibility of using the PillSense system (EnteraSense Ltd.), a novel diagnostic tool designed for the rapid in vivo detection of UGIB, in human volunteers. Methods: In the present study, 10 volunteers swallowed a PillSense capsule, followed by 2 servings of an autologous blood preparation. Participants were monitored for capsule passage, overall tolerability of the procedure, and adverse events. Results: The procedure was completed per the protocol established in the present study in 9/10 cases. In 9 of the subjects, after capsule ingestion, the device indicated the absence of blood with sensor output values of 1. After the ingestion of the first blood mixture, the sensor outputs of all devices increased to a range from 2.8 to 4, indicating that each sensor capsule detected blood. The sensor output remained within that range after the ingestion of the second mixture; however, in one case, the baseline capsule signal was positive, because of a preexisting condition. The passage of the capsule was verified in all patients, and no adverse events were reported. Conclusions: The first trial of the PillSense system in human subjects demonstrated the feasibility, safety, and tolerability of utilizing this product as a novel, noninvasive, and easy-to-use triage tool for the diagnosis of patients suspected of having UGIB.

Background:Tumor necrosis factor-alpha (TNF-α) agonists revolutionized therapeutic algorithms in inflammatory bowel disease (IBD) management. However, approximately every third IBD patient does not respond to this therapy in the long term, which delays efficient control of the intestinal inflammation.Methods:We analyzed the power of serum biomarkers to predict the failure of anti-TNF-α. We collected serum of 38 IBD patients at therapy prescription and 38 weeks later and analyzed them with relation to therapy response (no-, partial-, and full response). We used enzyme-linked immunosorbent assay to quantify 16 biomarkers related to gut barrier (intestinal fatty acid-binding protein, liver fatty acid-binding protein, trefoil factor 3, and interleukin (IL)-33), microbial translocation, immune system regulation (TNF-α, CD14, lipopolysaccharide-binding protein, mannan-binding lectin, IL-18, transforming growth factor-β1 (TGF-β1), osteoprotegerin (OPG), insulin-like growth factor 2 (IGF-2), endocrine-gland-derived vascular endothelial growth factor), and matrix metalloproteinase system (MMP-9, MMP-14, and tissue inhibitors of metalloproteinase-1).Results:We found that future full-responders have different biomarker profiles than non-responders, while partial-responders cannot be distinguished from either group. When future non-responders were compared to responders, their baseline contained significantly more TGF-β1, less CD14, and increased level of MMP-9, and concentration of these factors could predict non-responders with high accuracy (AUC = 0.938). Interestingly, during the 38 weeks, levels of MMP-9 decreased in all patients, irrespective of the outcome, while OPG, IGF-2, and TGF-β1 were higher in non-responders compared to full-responders both at the beginning and the end of the treatment.Conclusions:The TGF-β1 and CD14 can distinguish non-responders from responders. The changes in biomarker dynamics during the therapy suggest that growth factors (such as OPG, IGF-2, and TGF-β) are not markedly influenced by the treatment and that anti-TNF-α therapy decreases MMP-9 without influencing the treatment outcome.

Purpose Obesity and its related severe comorbidities are increasing rapidly. The duodenal-jejunal bypass is an endoscopically implanted device (mimicking the Roux-en-Y gastric bypass) developed to support weight reduction and improve type 2 diabetes control. Materials and Methods Retrospective data analysis of consecutive patients undergoing duodenal-jejunal bypass (EndoBarrier®, DJB) implantation between 2013 and 2017 was performed to evaluate safety as well as short- and long-term efficacy. Results One hundred and twenty-one patients (mean BMI of 43.1 ± 7.2 kg/m 2 and weight of 138.2 ± 28.6 kg) underwent DJB implantation. The mean dwelling time was 15.5 months, the mean total body weight loss (%TBWL) after explantation was 10.3% ± 7.9% (14.2 kg, p < 0.0001), and the mean BMI was 39.5 ± 7.3 kg/m 2 ( p < 0.0001). There was no significant weight gain 24 months after the explantation. Seventy-seven patients had type 2 diabetes mellitus (T2DM) with a mean HbA1c before implantation of 5.6% ( n = 52). The mean HbA1c after explantation was 5.1% ( p = 0.0001). Significant reductions in transaminase and lipid levels before and after explantation were observed. One complication occurred during implantation and another during explantation. In 16 patients, the device had to be extracted earlier than expected (7 for severe adverse events and 9 for adverse events; 13.2%). Conclusion Despite an evident rate of adverse events, the DJB shows promise as a weight-loss procedure. Our results show that some patients implanted with the device maintained reduced weight even 24 months after explantation, while many improved T2DM control. Graphical Abstract