Going Outside the Gut: Immune Thrombocytopenia Presenting as a Rare Extraintestinal Manifestation of Ulcerative Colitis.

A 26-year-old male with no significant medical history presented with hematochezia and was diagnosed with ulcerative colitis (UC) accompanied by immune thrombocytopenia (ITP) as an extraintestinal manifestation (EIM) of UC. This case report delves into the uncommon overlap between UC, a subtype of inflammatory bowel disease primarily affecting the colon and rectum, and ITP, an autoimmune condition leading to platelet destruction. The patient's atypical presentation and subsequent positive response to a treatment regimen targeting both UC and ITP underscores the necessity for a thorough and multifaceted diagnostic approach in individuals with UC, especially when faced with non-gastrointestinal symptoms like unexplained thrombocytopenia. The findings from this study enhance the understanding of UC's diverse manifestations and highlight its potential intersection with other autoimmune diseases, advocating for integrated care strategies in managing such intricate clinical cases.

Chronic Idiopathic Ulcers Mimicking Cecal Carcinoma: A Case Report.

Chronic idiopathic ulcers of the colon pose diagnostic challenges due to their elusive etiology and potential resemblance to other intestinal pathologies, such as cecal carcinoma. This case report outlines the clinical course of a 68-year-old female patient who presented to the emergency department (ED) with persistent right lower quadrant pain. Despite multiple hospital visits yielding varied diagnoses, a definitive diagnosis was only made following a laparoscopic partial colectomy, which revealed chronic idiopathic ulcers with transmural scarring and adhesions to adjacent small intestine loops. Histological examination demonstrated a substantial ulcer bed populated by inflammatory cells, including large stellate and spindled stromal cells within the granulation tissue, alongside lymphoid hyperplasia and scar tissue extending into the muscularis propria. The initial presentation of this case could easily be mistaken for appendicitis, diverticulitis, carcinoma, or irritable bowel syndrome, highlighting the significance of considering chronic idiopathic ulcers in the differential diagnosis of patients presenting with cecal masses.

Lichen Planopilaris As Part of Multiple Autoimmune Syndrome: A Case Report of New Association.

Lichen planopilaris (LPP) is an uncommon inflammatory scalp condition. Its typical clinical presentation includes scaly, erythematous plaques resulting in irreversible alopecia. In this study, we report a female in her late 30s with hypothyroidism and Crohn's disease. She presented with gradual, localized hair loss that had been ongoing for the past four months. A thorough physical examination, and complemented by dermoscopic evaluation, confirmed the diagnosis of LPP. Individuals who have an autoimmune disease (AID) have a heightened propensity to develop additional AID. The coexistence of three or more AIDs falls under the definition of multiple autoimmune syndrome (MAS). This is the first case, to the best of our knowledge, of LPP being associated with MAS.

Prevalence and Risk Factors of Clostridium difficile Infection Among Patients Hospitalized for a Flare of Inflammatory Bowel Disease in King Abdulaziz University Hospital.

Background The gram-negative anaerobe Clostridium difficile is the main infectious cause of pseudomembranous colitis and infectious diarrhea in hospitalized patients. Inflammatory bowel disease (IBD) patients have been proven to have higher rates of Clostridium difficile infection (CDI). Antibiotic use is the most well-known of the several risk factors for CDI. A few more are advanced age, previous hospitalization, increased severity of an underlying illness, gastrointestinal surgery, and proton pump inhibitors. This study aimed to find out which factors predict CDI in IBD patients at King Abdulaziz University Hospital in Jeddah. Methods We conducted a retrospective cohort study of all inflammatory bowel disease patients who developed CDI with a total sample of 602 patients from 2009 through 2022 at King Abdulaziz University in Jeddah, Saudi Arabia. We identified the clinical data of patients diagnosed with CDI and admitted to the hospital for either diagnosis or follow-up, and we measured the frequencies and percentages as qualitative data and the mean ( standard deviation) as quantitative variables. A chi-square test was used to estimate the correlation between Clostridium difficile infections and multiple factors, including a history of previous hospitalizations, recent flares, intestinal manifestations, extraintestinal manifestations, comorbidities, and IBD medications. Meanwhile, independent t-tests were performed to analyze the continuous variables. Results Out of 602 IBD patients, 53 patients (8.8%) had a confirmed CDI test using an immunoassay for Clostridium difficile toxins A and B. Most of the patients were female and nonsmokers. Regarding colonic involvement, 47 individuals with the disease extending to their large colon also evaluated positive for CDI. Among patients with a positive history of CDI, there were 21 patients with a recent flare-up of fewer than five episodes, five patients had more than five episodes, and the rest did not have any recent flare-ups. Also, IBD patients were significantly at a higher risk for intestinal resection. Conclusion IBD patients are more susceptible to CDI due to flare-ups that require hospitalization and their medications. As a result, clinicians must consider CDI testing in IBD patients who are hospitalized and who are receiving medication to ensure early diagnosis and therapy.

Crohn's Disease is a Greater Risk Factor for Nonalcoholic Fatty Liver Disease Compared to Ulcerative Colitis: A Systematic Review.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases that have been associated with nonalcoholic fatty liver disease (NAFLD). This systematic review aimed to examine whether Crohn's disease confers a greater risk for nonalcoholic fatty liver disease compared to ulcerative colitis. A comprehensive search of electronic databases from January 2000 to May 2023 was conducted to identify observational studies investigating the association between Crohn's disease or ulcerative colitis and nonalcoholic fatty liver disease. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 checklist ensured transparent reporting, and the Newcastle-Ottawa Scale was used to assess study quality. Data synthesis revealed higher nonalcoholic fatty liver disease prevalence among Crohn's disease patients compared to ulcerative colitis patients across regions. Ten studies published between 2016 and 2022, encompassing a total of 4164 participants from three continents, were included in the review. The median proportion of Crohn's disease patients with nonalcoholic fatty liver disease was 37.22% (range: 10.95-53.80%), while it was 27.55% (range: 8.60-46.20%) for ulcerative colitis patients. Subgroup analysis by region confirmed CD's higher NAFLD risk. Median proportions for CD patients who developed NAFLD from North America, Europe, and Asia were 25.97% (range: 14.6-37.33%), 47.01% (range: 14.2-53.8%), and 20.78% (range: 10.95-30.6%), respectively, and the median proportion of persons with UC who developed NAFLD in studies from North America, Europe, and Asia were 17.28% (range: 8.6-25.96%), 37.70% (range: 25.64-46.20%), and 19.52% (range: 10.14-28.90%), respectively. Variations suggest differing mechanisms, disease features, and therapeutics. Transmural inflammation in Crohn's disease may increase metabolic abnormalities, including nonalcoholic fatty liver disease. Geographic differences in lifestyle, genetics, and environmental variables may also contribute. This review demonstrates that Crohn's disease patients face a higher nonalcoholic fatty liver disease risk than ulcerative colitis patients, emphasizing the need for early monitoring and prevention. Further studies are warranted to understand mechanisms and develop tailored management approaches.

Diet as an Optional Treatment in Adults With Inflammatory Bowel Disease: A Systematic Review of the Literature.

While the exact cause of IBD is unknown, there are a number of factors that are thought to contribute to its development, including environmental and genetic factors. While exclusive enteral nutrition (EEN) is a promising therapy for Crohn's disease (CD), it is not yet considered a first-line treatment. Additionally, the efficacy of EEN compared to corticosteroid treatment is still being investigated. EEN is suggested as a first-line therapy by which guidelines and in which age groups, as it may differ in pediatric and adult recommendations. Another finding was that dietary changes involving an increase in anti-inflammatory foods and decreased intake of foods high in inflammatory compounds are linked to a beneficial outcome both metabolically and microbiologically in patients with ulcerative colitis (UC) in remission. For relevant medical literature, we examined PubMed/Medline, the Cochrane Library, and Google Scholar as examples of medical databases. The articles were identified, evaluated, and eligibility applied, and nine publications were found. The finished articles investigated the role of several diet alternatives for patients with IBD. Some others have shown that following a normal low-fat diet may be effective in reducing the occurrence of subclinical colitis. The EEN and partial enteral nutrition (PEN) indicated no significant differences between both regimens, but both had good outcomes during active IBD. Other strict diets, such as the specific carbohydrate diet (SCD) versus the Mediterranean diet (MD), demonstrate excellent outcomes in patients with IBD. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) dietary counseling improves gastrointestinal symptoms and quality of life in IBD patients. Based on the above, we concluded that more studies determining which component of the diet is not clear (proteins, carbs balanced) or diet types are required to establish a particular diet employed as a treatment intervention in these individuals.

Analysis of the interferon-γ-induced secretome of intestinal endothelial cells: putative impact on epithelial barrier dysfunction in IBD.

The development of inflammatory bowel diseases (IBD) involves the breakdown of two barriers: the epithelial barrier and the gut-vascular barrier (GVB). The destabilization of each barrier can promote initiation and progression of the disease. Interestingly, first evidence is available that both barriers are communicating through secreted factors that may accordingly serve as targets for therapeutic modulation of barrier functions. Interferon (IFN)-γ is among the major pathogenesis factors in IBD and can severely impair both barriers. In order to identify factors transmitting signals from the GVB to the epithelial cell barrier, we analyzed the secretome of IFN-γ-treated human intestinal endothelial cells (HIEC). To this goal, HIEC were isolated in high purity from normal colon tissues. HIEC were either untreated or stimulated with IFN-γ (10 U/mL). After 48 h, conditioned media (CM) were harvested and subjected to comparative hyper reaction monitoring mass spectrometry (HRM™ MS). In total, 1,084 human proteins were detected in the HIEC-CM. Among these, 43 proteins were present in significantly different concentrations between the CM of IFN-γ- and control-stimulated HIEC. Several of these proteins were also differentially expressed in various murine colitis models as compared to healthy animals supporting the relevance of these proteins secreted by inflammatory activated HIEC in the inter-barrier communication in IBD. The angiocrine pathogenic impact of these differentially secreted HIEC proteins on the epithelial cell barrier and their perspectives as targets to treat IBD by modulation of trans-barrier communication is discussed in detail.

Protective potential of the gallbladder in primary sclerosing cholangitis.

Background & Aims: Gallbladder enlargement is common in patients with primary sclerosing cholangitis (PSC). The gallbladder may confer hepatoprotection against bile acid overload, through the sequestration and cholecystohepatic shunt of bile acids. The aim of this study was to assess the potential impact of the gallbladder on disease features and bile acid homeostasis in PSC. Methods: Patients with PSC from a single tertiary center who underwent liver MRI with three-dimensional cholangiography and concomitant analyses of serum bile acids were included. Gallbladder volume was measured by MRI and a cut-off of 50 ml was used to define gallbladder enlargement. Bile acid profiles and PSC severity, as assessed by blood tests and MRI features, were compared among patients according to gallbladder size (enlarged vs. normal-sized) or presence (removed vs. conserved). The impact of cholecystectomy was also assessed in the Abcb4 knockout mouse model of PSC. Results: Sixty-one patients with PSC, all treated with ursodeoxycholic acid (UDCA), were included. The gallbladder was enlarged in 30 patients, whereas 11 patients had been previously cholecystectomized. Patients with enlarged gallbladders had significantly lower alkaline phosphatase, a lower tauro-vs. glycoconjugate ratio and a higher UDCA vs. total bile acid ratio compared to those with normal-sized gallbladders. In addition, gallbladder volume negatively correlated with the hydrophobicity index of bile acids. Cholecystectomized patients displayed significantly higher aspartate aminotransferase and more severe bile duct strictures and dilatations compared to those with conserved gallbladder. In the Abcb4 knockout mice, cholecystectomy caused an increase in hepatic bile acid content and in circulating secondary bile acids, and an aggravation in cholangitis, inflammation and liver fibrosis. Conclusion: Altogether, our findings indicate that the gallbladder fulfills protective functions in PSC. Impact and implications: In patients with primary sclerosing cholangitis (PSC), gallbladder status impacts on bile acid homeostasis and disease features. We found evidence of lessened bile acid toxicity in patients with PSC and enlarged gallbladders and of increased disease severity in those who were previously cholecystectomized. In the Abcb4 knockout mouse model of PSC, cholecystectomy causes an aggravation of cholangitis and liver fibrosis. Overall, our results suggest that the gallbladder plays a protective role in PSC.

Spectrum of Autoimmune Liver Disease and Real-World Treatment Experience from a Tertiary Care Hospital.

Background and aims: Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India. Methods: A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC. Results: Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000-1.003], P = 0.034), high albumin (OR 1.91 [1.05-3.48], P = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33-0.91], P = 0.020) predicted complete response. Conclusion: AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response.

Post-Transplant Immunosuppression in Autoimmune Liver Disease.

Autoimmune liver diseases (AILDs) are a group of conditions where immune-mediated liver damage can lead to the need for transplantation. Collectively, they account for almost a quarter of all liver transplants. Outcomes in terms of graft and patient survival for all liver transplants have improved markedly over decades with improvements in patient selection, surgical techniques and longer-term care and this is also seen in patients with AILDs. The current five- and ten-year survival rates post-transplant in autoimmune disease are excellent, at 88% and 78%, respectively. A key factor in maintaining good outcomes post liver transplant for these autoimmune conditions is the immunosuppression strategy. These patients have increased the rates of rejection, and autoimmune conditions can all recur in the graft ranging from 12 to 60% depending on the population studied. Immunosuppressive regimens are centred on calcineurin inhibitors, often combined with low dose corticosteroids, with or without the addition of antimetabolite therapy. There is no clear evidence-based immunosuppressive regimen for these conditions, and a tailored approach balancing the individuals' immunological profile against the risks of immunosuppression is often used. There are disease-specific considerations to optimised graft function including the role of ursodeoxycholic acid in both primary biliary cholangitis and primary sclerosing cholangitis and the role and timing of colectomy in primary sclerosing cholangitis in inflammatory bowel disease patients. However, unmet needs still exist in the management of AILDs post liver transplantation particularly in building the evidence base for optimal immunosuppression as well as mitigating the risk of recurrent disease.

Cerebral venous thrombosis secondary to ulcerative colitis: A case report with a literature review.

Ulcerative colitis is an idiopathic inflammatory bowel condition that may be worsened by thromboembolic events such deep vein thrombosis, cerebral venous thrombosis, and pulmonary embolism. Cerebral venous thrombosis is a rare but critical consequence of ulcerative colitis characterized by high mortality and morbidity rate. It is thought to be caused by the hypercoagulable state that occurs during ulcerative colitis relapse. Cerebral venous thrombosis is a reversible condition with good outcomes when detected early and treated properly. In this study, we describe the case of a young woman who presented with cerebral venous thrombosis secondary to ulcerative colitis complicated by venous infarction with petechial cerebral hemorrhage.

Risk of SARS-CoV-2 infection in healthcare workers with inflammatory bowel disease: a case-control study.

Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of Novel coronavirus disease (COVID-19) due to occupational exposure is unknown. Aim: To assess the risk of COVID-19 in healthcare workers with IBD. Methods: A case control study enrolled 326 healthcare workers with IBD from 17 GETAID centres and matched non-healthcare workers with IBD controls (1:1) for gender, age, disease subtype and year of diagnosis. The study period was year 2020 during the COVID-19 outbreak. Results: In total, 59 COVID-19 were recorded among cases (n = 32) and controls (n = 27), including 2 severe COVID-19 (requiring hospitalization, mechanic ventilation) but no death. No difference was observed between healthcare workers and controls regarding the overall incidence rates of COVID-19 4.9 ± 2.2 vs. 3.8 ± 1.9 per 100 patient-semesters, P = 0.34) and the overall incidence rates of severe COVID-19 (0.6 ± 7.8 vs. 0.3 ± 5.5 per 100 patient-semesters, P = 0.42). In multivariate analysis in the entire study population, COVID-19 was associated with patients with body mass index > 30 kg/m2 (HR = 2.48, 95%CI [1.13-5.44], P = 0.02). Conclusion: Healthcare workers with IBD do not have an increased risk of COVID-19 compared with other patients with IBD.

Impact of hematopoietic stem cell transplantation in glycogen storage disease type Ib: A single-subject research design using 13C-glucose breath test.

Background: Glycogen storage disease type Ib (GSD Ib) is an autosomal recessively inherited deficiency of the glucose-6-phosphate translocase (G6PT). Clinical features include a combination of a metabolic phenotype (fasting hypoglycemia, lactic acidosis, hepatomegaly) and a hematologic phenotype with neutropenia and neutrophil dysfunction. Dietary treatment involves provision of starches such as uncooked cornstarch (UCCS) and Glycosade® to provide prolonged enteral supply of glucose. Granulocyte colony-stimulating factor (G-CSF) is the treatment of choice for neutropenia. Because long-term stimulation of hematopoiesis with G-CSF causes serious complications such as splenomegaly, hypersplenism, and osteopenia; hematopoietic stem cell transplantation (HSCT) has been considered in some patients with GSD Ib to correct neutropenia and avoid G-CSF related adverse effects. Whether HSCT also has an effect on the metabolic phenotype and utilization of carbohydrate sources has not been determined. Objective: Our objective was to measure the utilization of starch in a patient with GSD Ib before and after HSCT using the minimally invasive 13C-glucose breath test (13C-GBT). Design: A case of GSD Ib (18y; female) underwent 13C-GBT four times: UCCS (pre-HSCT), UCCS (3, 5 months post-HSCT) and Glycosade® (6 months post-HSCT) with a dose of 80 g administered via nasogastric tube after a 4 h fast according to our patient's fasting tolerance. Breath samples were collected at baseline and every 30 min for 240 min. Rate of CO2 production was measured at 120 min using indirect calorimetry. Finger-prick blood glucose was measured using a glucometer hourly to test hypoglycemia (glucose <4 mmol/L). Biochemical and clinical data were obtained from the medical records as a post-hoc chart review. Results: UCCS utilization was significantly higher in GSD Ib pre-HSCT, which reduced and stabilized 5 months post-HSCT. UCCS and Glycosade® utilizations were low and not different at 5 and 6 months post-HSCT. Blood glucose concentrations were not significantly different at any time point. Conclusions: Findings show that HSCT stabilized UCCS utilization, as reflected by lower and stable glucose oxidation. The results also illustrate the application of 13C-GBT to examine glucose metabolism in response to various carbohydrate sources after other treatment modalities like HSCT in GSD Ib.

The impact of the COVID-19 pandemic on the mental health of patients diagnosed with inflammatory bowel diseases.

Understanding the profound impact of a viral pandemic on the mental health of patients with autoimmune diseases undergoing biological treatment is crucial for future insights. This cross-sectional case-control study aimed to assess the mental health implications of the COVID-19 pandemic on individuals with inflammatory bowel disease (IBD) in Romania, spanning from November 2022 to March 2023. A specialized self-report questionnaire in the Romanian language was developed to measure the multifaceted effects of COVID-19 on the mental well-being of these patients. The findings revealed a significant decline in the mental health of patients with IBD during the pandemic compared to the control group. Patients with IBD exhibited elevated levels of anxiety and concern regarding the virus. Intriguingly, despite the challenges, the vaccination rate was notably higher among patients with IBD, indicating a proactive approach to safeguarding their health. The study also shed light on various coping mechanisms employed by patients with IBD to navigate the pandemic-related restrictions. Engaging in activities such as social media and computer games emerged as effective strategies for managing heightened stress and limitations. In conclusion, the emergence of a novel viral pathogen represents a significant distress factor for patients with autoimmune diseases. Recognizing and comprehending these consequences enhances our understanding of the intricate interplay between physical and mental health and equips authorities with valuable insights to better manage future epidemics or viral outbreaks. This study underscores the importance of tailored support systems and strategies for patients with autoimmune diseases during global health crises.

Assessing the effect of interaction between gut microbiome and inflammatory bowel disease on the risks of depression.

Background: Gut microbiome and inflammatory bowel disease (IBD) are implicated in the development of depression, but the effect of their interactions on the risk of depression remains unclear. We aim to analyze the effect of interactions between gut microbiome and IBD on the risk of depression, and explore candidate genes involving the interactions. Methods: Using the individual genotype and depression traits data from the UK Biobank, we calculated the polygenetic risk scores (PRS) of 114 gut microbiome, ulcerative colitis (UC), Crohn's disease (CD), and total IBD (CD + UC) respectively. The effects of interactions between gut microbiome and IBD on depression were assessed through a linear regression model. Moreover, for observed significant interactions between gut microbiome PRS and IBD PRS, PLINK software was used to test pair-wise single nucleotide polymorphisms (SNPs) interaction of corresponding gut microbiome PRS and IBD PRS on depression. Results: We found 64 candidate interactions between gut microbiome and IBD on four phenotypes of depression, such as F_Lachnospiraceae (RNT) × (CD + UC) for patient health questionnaire-9 (PHQ-9) score (P = 1.48 × 10-3), F_Veillonellaceae (HB) × UC for self-reported depression (P = 2.83 × 10-3) and P_Firmicutes (RNT) × CD for age at first episode of depression (P = 8.50 × 10-3). We observed interactions of gut-microbiome-associated SNPs × IBD-associated SNPs, such as G_Alloprevotella (HB)-associated rs147650986 (GPM6A) × IBD-associated rs114471990 (QRICH1) (P = 2.26 × 10-4). Conclusion: Our results support the effects of interactions between gut microbiome and IBD on depression risk, and reported several novel candidate genes for depression.

ITCH deficiency clinical phenotype expansion and mitochondrial dysfunction.

Autoimmune Disease, Multisystem, with Facial Dysmorphism (ADMFD) is an autosomal recessive disorder due to pathogenic variants in the ITCH gene. It is characterized by failure to thrive, dysmorphic facial features, developmental delay, and systemic autoimmunity that can manifest variably with autoimmune hepatitis, thyroiditis, and enteropathy, among other organ manifestations. It was originally described in 10 consanguineous Old Order Amish patients, and more recently in two patients of White British and Black German ethnicities. While the role of ITCH protein in apoptosis and inflammation has previously been characterized, a defect in cellular bioenergetics has not yet been reported in ITCH deficiency. Here we present a Caucasian female originally evaluated for possible mitochondrial respiratory chain deficiency, who ultimately was found to have two novel variants in ITCH with absence of ITCH protein in patient derived fibroblasts. Clinical studies of patient muscle showed mitochondrial DNA copy number of 57% compared to controls. Functional studies in skin fibroblasts revealed decreased activity of mitochondrial fatty acid oxidation and oxidative phosphorylation, and decreased overall ATP production. Our findings confirm mitochondrial energy dysfunction in a patient with ITCH deficiency offering the opportunity to assess alternative therapeutic options.

Inflammatory conditions play a role in recurrence of PSC after liver transplantation: An international multicentre study.

Background & Aims: Liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complicated by recurrence of PSC (rPSC) in up to 25% of recipients. Recurrence has been shown to be detrimental for both graft and patient survival. For both PSC and rPSC, a medical cure is not available. To predict and ideally to prevent rPSC, it is imperative to find risk factors for rPSC that can be potentially modified. Therefore, we aimed to identify such factors for rPSC in a large international multicentre study including 6 centres in PSC-prevalent countries. Methods: In this international multicentre, retrospective cohort study, 531 patients who underwent transplantation for PSC were included. In 25% of cases (n = 131), rPSC was diagnosed after a median follow-up of 6.72 (3.29-10.11) years post-LT. Results: In the multivariable competing risk model with time-dependent covariates, we found that factors representing an increased inflammatory state increase the risk for rPSC. Recurrent cholangitis before LT as indication for LT (hazard ratio [HR] 3.6, 95% CI 2.5-5.2), increased activity of inflammatory bowel disease after LT (HR 1.7, 95% CI 1.08-2.75), and multiple acute cellular rejections (HR: non-linear) were significantly and independently associated with an increased risk of rPSC. In contrast to the findings of previous studies, pretransplant colectomy was not found to be independently protective against the development of rPSC. Conclusions: An increased inflammatory state before and after LT may play a causal and modifiable role in the development of rPSC. Pretransplant colectomy did not reduce the risk of rPSC per se. Recurrent cholangitis as indication for LT was associated with an increased risk of rPSC. Impact and implications: Recurrence of PSC (rPSC) negatively affects survival after liver transplant (LT). Modifiable risk factors could guide clinical management and prevention of rPSC. We demonstrate that an increased inflammatory state both before and after LT increases the incidence of rPSC. As these are modifiable factors, they could serve as targets for future studies and therapies. We also added further evidence to the ongoing debate regarding preventive colectomy for rPSC by reporting that in our multicenter study, we could not find an independent association between colectomy and risk of rPSC.

Integrated gut microbiome and metabolome analyses identified fecal biomarkers for bowel movement regulation by Bifidobacterium longum BB536 supplementation: A RCT.

Background: Bifidobacterium longum BB536 supplementation can be used to regulate bowel movements in various people, including healthy subjects and patients with irritable bowel syndrome (IBS); however, individuals vary in their responses to B. longum BB536 treatment. One putative factor is the gut microbiota; recent studies have reported that the gut microbiota mediates the effects of diet or drugs on the host. Here, we investigated intestinal features, such as the microbiome and metabolome, related to B. longum BB536 effectiveness in increasing bowel movement frequency. Results: A randomized, double-blind controlled crossover trial was conducted with 24 adults who mainly tended to be constipated. The subjects received a two-week dietary intervention consisting of B. longum BB536 in acid-resistant seamless capsules or similarly encapsulated starch powder as the placebo control. Bowel movement frequency was recorded daily, and fecal samples were collected at several time points, and analyzed by metabologenomic approach that consists of an integrated analysis of metabolome data obtained using mass spectrometry and microbiome data obtained using high-throughput sequencing. There were differences among subjects in B. longum intake-induced bowel movement frequency. The responders were predicted by machine learning based on the microbiome and metabolome features of the fecal samples collected before B. longum intake. The abundances of eight bacterial genera were significantly different between responders and nonresponders. Conclusions: Intestinal microbiome and metabolome profiles might be utilized as potential markers of improved bowel movement after B. longum BB536 supplementation. These findings have implications for the development of personalized probiotic treatments.