Prevalence of Hepatobiliary Manifestations in Inflammatory Bowel Disease: A GRADE Assessed Systematic Review and Meta-Analysis of more than 1.7 Million Patients.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] comprises an immune-mediated group of chronic gastrointestinal disorders. Patients with IBD may experience extraintestinal manifestations, such as hepatobiliary complications. This meta-analysis aims to assess the prevalence of different hepatic manifestations in IBD patients. METHODS: For this systematic review and meta-analysis, PubMed, Scopus, Web of Science, and Embase were searched until July 20, 2022, by specifying keywords for IBD, hepatic manifestations, and study type. Full texts of cohort studies in English that examined the prevalence of different hepatic manifestations were included in this study. The primary outcome was the overall prevalence of hepatic manifestations in IBD patients. For the statistical analysis, a proportion by random effect model meta-analysis was performed. The registration number for the protocol of this study in PROSPERO is CRD42022369595. RESULTS: From the 4421 articles retrieved from the primary search, 118 met the inclusion criteria and were included in the final analysis. After a pooled analysis of 1 729 128 patients, the overall prevalence of hepatic manifestations was 3.49% (95% confidence interval [CI]: 3.31-3.68%; I2: 99.55%). The pooled prevalence of non-alcoholic fatty liver disease in 228 216 patients was 26.1% [95% CI: 22.1-30.2%; I2: 99.018%]. After pooled analysis of 9642 patients, the prevalence of primary sclerosing cholangitis was 1.67% [95% CI: 1.47-1.88%; I2: 99.10%]. The pooled prevalence of biliary stones was 4.1% [95% CI: 3.6-4.7%; I2: 97.43%]. Autoimmune hepatitis (0.51% [95% CI: 0.26-0.75%]; I2: 85.36%) and portal vein thrombosis (0.21% [95% CI: 0.08-0.33%]; I2: 97.95%) are considered as rare manifestations. CONCLUSION: This study summarizes the prevalence and importance of different hepatic manifestations in IBD patients. These findings are crucial for the management of extraintestinal manifestations, especially hepatic manifestations, in IBD patients.

Genetic modification and preconditioning strategies to enhance functionality of mesenchymal stromal cells: a clinical perspective.

INTRODUCTION: Mesenchymal stromal cell (MSC)-based therapy has generated great hope for the treatment of various diseases such as myocardial infarction and stroke. Unfortunately, MSC-based therapy faces major hurdles in its translation to clinical practice. To address these issues, preconditioning and genetic modification strategies have been developed. Through preconditioning, MSCs are cultured under sub-lethal conditions of environmental stresses or treated with specific drugs, biomolecules, and growth factors. Genetic modification is a procedure in which specific genetic sequences are transferred into the MSCs via viral vectors or CRISP/Cas9 in order to alter the expression of distinctive genes. AREAS COVERED: In this article, a comprehensive review on preconditioning and gene modification inducers, mechanisms of action, and their impacts were discussed. In addition, clinical trials that used preconditioned and genetic modified MSCs are debated. EXPERT OPINION: Numerous preclinical investigations have demonstrated that preconditioning and genetic modifications considerably enhance MSC's therapeutic capacity through improving their survival rate, antioxidant activity, growth factor secretion, immunomodulation, homing efficiency, and angiogenesis. For MSC preconditioning and genetic modification to achieve clinical translation, remarkable outcomes in clinical trials are of pivotal importance.

Clinical and laboratory findings following transplantation of allogeneic adipose-derived mesenchymal stromal cells in knee osteoarthritis, a brief report.

BACKGROUND: Mesenchymal stromal cells (MSCs) injection has been proposed as an innovative treatment for knee osteoarthritis (KOA). Since, allogeneic MSCs can be available as off-the-shelf products, they are preferable in regenerative medicine. Among different sources for MSCs, adipose-derived MSCs (AD-MSCs) appear to be more available. METHODS: Three patients with KOA were enrolled in this study. A total number of 100 × 106 AD-MSCs was injected intra-articularly, per affected knee. They were followed up for 6 months by the assessment of clinical outcomes, magnetic resonance imaging (MRI), and serum inflammatory biomarkers. RESULTS: The primary outcome of this study was safety and feasibility of allogeneic AD-MSCs injection during the 6 months follow-up. Fortunately, no serious adverse events (SAEs) were reported. Assessment of secondary outcomes of visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and knee osteoarthritis outcome score (KOOS) indicated improvement in all patients. Comparison between baseline and endpoint findings of MRI demonstrated a slight improvement in two patients. In addition, decrease in serum cartilage oligomeric matrix protein (COMP) and hyaluronic acid (HA) indicated the possibility of reduced cartilage degeneration. Moreover, quantification of serum interleukin-10 (IL-10) and interleukin-6 (IL-6) levels indicated that the host immune system immunomodulated after infusion of AD-MSCs. CONCLUSION: Intra-articular injection of AD-MSCs is safe and could be effective in cartilage regeneration in KOA. Preliminary assessment after six-month follow-up suggests the potential efficacy of this intervention which would need to be confirmed in randomized controlled trials on a larger population. TRIAL REGISTRATION: This study was registered in the Iranian registry of clinical trials (https://en.irct.ir/trial/46) in 24 April 2018 with identifier IRCT20080728001031N23.

PSC associated inflammatory bowel disease: a distinct entity.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a rare, chronic, and progressive cholestatic disease involving intra- and/or extrahepatic bile ducts. PSC in many patients results in end-stage liver diseases. Nearly 60% of the PSC patients suffer from concomitant inflammatory bowel diseases (IBDs). Classically, IBDs are divided into two principle types: Crohn's disease (CD) and ulcerative colitis (UC). However, with growing knowledge, PSC-associated IBD (PSC-IBD) seems to be a rather distinct entity with specific genetics, clinical, and microbiota characteristics. AREAS COVERED: In this article, we aim to review the unique characteristics of PSC-IBD from clinical, genetic, and microbiota point of view. EXPERT OPINION: PSC-IBD's unique characteristics contribute to the notion that it could be a distinct entity. Acknowledgment of PSC-IBD as a novel entity necessitates designing new clinical guidelines for diagnosis and developing novel therapies.

Gut mycobiome: The probable determinative role of fungi in IBD patients.

Inflammatory bowel disease (IBD) is a multi-factorial autoimmune disorder that its causative agents are unknown. The gut microbiota comprises of bacteria, viruses, fungi and protozoa that its role in IBD has remained controversially. Bacteria constitute more than 99% of the gut microbiota composition, and the main core of the gut microbiota is composed from Bacteroidetes and Firmicutes. The gut microbiota plays an important role in training, development and haemostasis of the immune responses during the life. Fungi compose a very small portion of gut microbiota, but play determinative roles in homeostasis of the gut bacterial composition and the mucosal immune responses. An interkingdom correlation between bacteria and fungi has been suggested. For example, the presence of Salmonella enterica serovar Typhimurium reduces the viability and colonisation of C albicans. Alterations in the composition and function of the gut microbiota, which is known as dysbiosis, are a usual event in patients who suffer from IBD. Although the main reason for this alteration is not clear, the interaction between gut bacteria and gut fungi seems to be an important subject in IBD patients. This review covers new findings on the interaction between fungi and bacteria and the role of fungi in the pathophysiology of IBD.