Management of Post-Operative Crohn's Disease: Knowns and Unknowns.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by relapsing-remission phases. CD often requires surgical intervention during its course, mainly ileo-cecal/ileo-colonic resection. However, surgery in CD is not curative and post-operative recurrence (POR) can happen. The management of CD after surgery presents challenges. Ensuring timely, effective, and safe therapy to prevent POR is essential but difficult, considering that approximately 20-30% of subjects may not experience endoscopic POR and that 40-50% will only exhibit intermediate lesions, which carry a low risk of mid- and long-term clinical and surgical POR. Currently, there are two accepted intervention strategies: early post-operative prophylactic therapy (systematically or based on the patient's risk of recurrence) or starting therapy after confirming endoscopic POR 6-12 months after surgery (endoscopy-driven prophylactic therapy). The risk of overtreatment lies in exposing patients to undesired adverse events, along with the costs associated with medications. Conversely, undertreatment may lead to missed opportunities to prevent bowel damage and the necessity for additional surgery. This article aims to perform a comprehensive review regarding the optimal strategy to reduce the risk of POR in CD patients and the current therapeutic options.

Ophthalmological Manifestations in Inflammatory Bowel Diseases: Keep an Eye on It.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not least, the eye. Approximately 10% of IBD patients can develop ocular EIMs (O-EIMs) with a higher prevalence in Crohn's disease (CD). Eye-redness, photophobia, pain, and blurred vision are the common symptoms, with a wide rate of severity and clinical impact on the quality of life. This narrative review aims to summarize the prevalence, pathogenesis, and current evidence-based management of O-EIMs, underlying the importance of a holistic approach and specialties collaboration for a prompt diagnosis and treatment. METHODS: PubMed was searched up to December 2023 to identify relevant studies investigating the pathogenesis, epidemiology, and treatment of O-EIMs in IBD patients. RESULTS: The mechanisms underlying O-EIMs are partially unknown, encompassing immune dysregulation, shared antigens between the eye and the gut, genetic predisposition, and systemic inflammation driven by high levels of interleukins and cytokines in IBD patients. The complexity of O-EIMs' pathogenesis reflects in the management of these conditions, varying from topical and systemic steroids to immunomodulatory molecules and biologic therapy, such as anti-tumor necrosis factor (TNF)-alpha. A multidisciplinary approach is the backbone of the management of O-EIMs.

Exploring the link: Porto-sinusoidal vascular disorder and inflammatory bowel disease - A comprehensive narrative review.

Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions involving the portal venules and sinusoids, independent of the presence of portal hypertension (PH), and for which liver biopsy is essential for diagnosis. PSVD has been shown to be common in patients with immune-mediated diseases, including inflammatory bowel disease (IBD). The association between PSVD and the use of thiopurines and thioguanine in patients with IBD has been well established. In addition, research suggests an association between PSVD and IBD, even in cases where patients haven't been exposed to specific medications, probably related to changes in intestinal permeability. The identification and management of patients with known IBD and PSVD is a challenge for gastroenterologists. This narrative review aims to summarize the currently available data on the association between IBD and PSVD and provide practical suggestions for the management of this group of patients.

Treat-to-Target and Regular Surveillance of Inflammatory Bowel Disease Are Associated with Low Incidence and Early-Stage Detection of Malignancies: A Retrospective Cohort Study.

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), increase the risk of malignancies, particularly colorectal cancer (CRC). We aimed to assess the incidence of malignancies in IBD patients managed using a treat-to-target approach and recommended surveillance. We retrospectively searched the electronic databases of two tertiary IBD centers in Milan from 2010 to 2019 for new diagnoses of malignancy in patients with pre-existing IBD. A total of 5239 patients with a follow-up of 19,820 years were included. In total, 71 malignancies were diagnosed in 70 patients (38 CD, 32 UC) with a mean age of 52.9 years, of whom 64% were former or active smokers. The annual incidence of all malignancies was 358 per 100,000 patient years (95% CI 275-444), and the standardized incidence rate (SIR) was 0.93 (95% CI 0.73-1.16). Gastrointestinal cancers were the most frequent (n = 17, 23.9%), in particular, CRC (n = 9), with an incidence of 45 per 100,000 (95% CI 15-74) and an SIR of 1.18 (95% CI 0.54-2.09). CRC occurred mainly in UC patients (6/8), while small bowel cancer was seen in CD patients (5/9). Melanoma and breast cancer (n = 8 each) were the most common non-GI cancers. No significant difference in incidence was found between CD or UC. Death occurred in nine patients (11%) and was due to cancer in eight of these cases, two of which were IBD-related. Most malignancies included in the surveillance were diagnosed at early (I-II) stages (20 vs. 4, p < 0.05). In patients with IBD, treat-to-target and strict surveillance were associated with a low incidence of cancer, similar to that of the general population, and the detection of malignancies at an early stage.

Lung Involvement in Inflammatory Bowel Diseases: Shared Pathways and Unwanted Connections.

Inflammatory bowel diseases (IBDs) are chronic, relapsing inflammatory disorders of the gastrointestinal tract, frequently associated with extraintestinal manifestations (EIMs) that can severely affect IBD patients' quality of life, sometimes even becoming life-threatening. Respiratory diseases have always been considered a rare and subsequently neglected extraintestinal manifestations of IBD. However, increasing evidence has demonstrated that respiratory involvement is frequent in IBD patients, even in the absence of respiratory symptoms. Airway inflammation is the most common milieu of IBD-related involvement, with bronchiectasis being the most common manifestation. Furthermore, significant differences in prevalence and types of involvement are present between Crohn's disease and ulcerative colitis. The same embryological origin of respiratory and gastrointestinal tissue, in addition to exposure to common antigens and cytokine networks, may all play a potential role in the respiratory involvement. Furthermore, other causes such as drug-related toxicity and infections must always be considered. This article aims at reviewing the current evidence on the association between IBD and respiratory diseases. The purpose is to raise awareness of respiratory manifestation among IBD specialists and emphasize the need for identifying respiratory diseases in early stages to promptly treat these conditions, avoid worsening morbidity, and prevent lung damage.

Checkpoint Inhibitor-Induced Colitis: From Pathogenesis to Management.

The advent of immunotherapy, specifically of immune checkpoint inhibitors (ICIs), for the treatment of solid tumors has deeply transformed therapeutic algorithms in medical oncology. Approximately one-third of patients treated with ICIs may de velop immune-related adverse events, and the gastrointestinal tract is often affected by different grades of mucosal inflammation. Checkpoint inhibitors colitis (CIC) presents with watery or bloody diarrhea and, in the case of severe symptoms, requires ICIs discontinuation. The pathogenesis of CIC is multifactorial and still partially unknown: anti-tumor activity that collaterally effects the colonic tissue and the upregulation of specific systemic inflammatory pathways (i.e., CD8+ cytotoxic and CD4+ T lymphocytes) are mainly involved. Many questions remain regarding treatment timing and options, and biological treatment, especially with anti-TNF alpha, can be offered to these patients with the aim of rapidly resuming oncological therapies. CIC shares similar pathogenesis and aspects with inflammatory bowel disease (IBD) and the use of ICI in IBD patients is under evaluation. This review aims to summarize the pathogenetic mechanism underlying CIC and to discuss the current evidenced-based management options, including the role of biological therapy, emphasizing the relevant clinical impact on CIC and the need for prompt recognition and treatment.

Atherosclerotic cardiovascular diseases in inflammatory bowel diseases: to the heart of the issue.

Atherosclerotic cardiovascular disease and stroke are the leading causes of morbidity and mortality worldwide. Along to the traditional risk factors for these diseases, chronic inflammation is known to be an important player in accelerating the process of atherosclerosis, which can result in an increased incidence of arterial thromboembolic events. As in other chronic inflammatory diseases, in the past few years, several studies suggested that subjects affected by inflammatory bowel diseases (IBD) may also be at an incremented risk of atherosclerotic disease, especially during the periods of disease's flare. Therefore, IBD treatment may assume an important role for achieving both disease remission and the control of the atherosclerotic risk. In this article we aimed to perform a comprehensive review on evidence on the increased risk of arterial thromboembolic events in patients affected by IBD and discuss the potential role of IBD therapy in reducing this risk.

Fibro-Stenosing Crohn's Disease: What Is New and What Is Next?

Fibro-stenosing Crohn's disease (CD) is a common disease presentation that leads to impaired quality of life and often requires endoscopic treatments or surgery. From a pathobiology perspective, the conventional view that intestinal fibro-stenosis is an irreversible condition has been disproved. Currently, there are no existing imaging techniques that can accurately quantify the amount of fibrosis within a stricture, and managing patients is challenging, requiring a multidisciplinary team. Novel therapies targeting different molecular components of the fibrotic pathways are increasing regarding other diseases outside the gut. However, a large gap between clinical need and the lack of anti-fibrotic agents in CD remains. This paper reviews the current state of pathobiology behind fibro-stenosing CD, provides an updated diagnostic and therapeutic approach, and finally, focuses on clinical trial endpoints and possible targets of anti-fibrotic therapies.

Pomegranate Extract Affects Gut Biofilm Forming Bacteria and Promotes Intestinal Mucosal Healing Regulating the Crosstalk between Epithelial Cells and Intestinal Fibroblasts.

Background: Pomegranate (Punica granatum) can be used to prepare a bioactive extract exerting anti-inflammatory activities. Clinical studies demonstrated an improvement in clinical response in inflammatory bowel disease (IBD) patients when pomegranate extract (PG) was taken as a complement to standard medications. However, the molecular mechanisms underlying its beneficial effects are still scarcely investigated. This study investigates the effect of PG on bacterial biofilm formation and the promotion of mucosal wound healing. Methods: The acute colitis model was induced in C57BL/6N mice by 3% dextran sodium sulfate administration in drinking water for 5 days. During the recovery phase of colitis, mice received saline or PG (200 mg/kg body weight) by oral gavage for 11 days. Colitis was scored daily by evaluating body weight loss, bleeding, and stool consistency. In vivo intestinal permeability was evaluated by fluorescein isothiocyanate-conjugated dextran assay, bacterial translocation was assessed by fluorescence in situ hybridization on tissues, whereas epithelial and mucus integrity were monitored by immunostaining for JAM-A and MUC-2 markers. Bacterial biofilm formation was assessed using microfluidic devices for 24 or 48 h. Primary fibroblasts were isolated from healthy and inflamed areas of 8 IBD patients, and Caco-2 cells were stimulated with or without PG (5 µg/mL). Inflammatory mediators were measured at the mRNA and protein level by RT-PCR, WB, or Bio-plex multiplex immunoassay, respectively. Results: In vivo, PG boosted the recovery phase of colitis, promoting a complete restoration of the intestinal barrier with the regeneration of the mucus layer, as also demonstrated by the absence of bacterial spread into the mucosa and the enrichment of crypt-associated fibroblasts. Microfluidic experiments did not highlight a specific effect of PG on Enterobacterales biofilm formation, even though Citrobacter freundii biofilm was slightly impaired in the presence of PG. In vitro, inflamed fibroblasts responded to PG by downregulating the release of metalloproteinases, IL-6, and IL-8 and upregulating the levels of HGF. Caco-2 cells cultured in a medium supplemented with PG increased the expression of SOX-9 and CD44, whereas in the presence of HGF or plated with a fibroblast-conditioned medium, they displayed a decrease in SOX-9 and CD44 expression and an increase in AXIN2, a negative regulator of Wnt signaling. Conclusions: These data provide new insight into the manifold effects of PG on promoting mucosal homeostasis in IBD by affecting pathogen biofilm formation and favoring the regeneration of the intestinal barrier through the regulation of the crosstalk between epithelial and stromal cells.

Mental Illnesses in Inflammatory Bowel Diseases: mens sana in corpore sano.

Background and aims: Inflammatory bowel diseases (IBD) are chronic disorders associated with a reduced quality of life, and patients often also suffer from psychiatric comorbidities. Overall, both mood and cognitive disorders are prevalent in chronic organic diseases, especially in the case of a strong immune component, such as rheumatoid arthritis, multiple sclerosis, and cancer. Divergent data regarding the true incidence and prevalence of mental disorders in patients with IBD are available. We aimed to review the current evidence on the topic and the burden of mental illness in IBD patients, the role of the brain-gut axis in their co-existence, and its implication in an integrated clinical management. Methods: PubMed was searched to identify relevant studies investigating the gut-brain interactions and the incidence and prevalence of psychiatric disorders, especially of depression, anxiety, and cognitive dysfunction in the IBD population. Results: Among IBD patients, there is a high prevalence of psychiatric comorbidities, especially of anxiety and depression. Approximately 20-30% of IBD patients are affected by mood disorders and/or present with anxiety symptoms. Furthermore, it has been observed that the prevalence of mental illnesses increases in patients with active intestinal disease. Psychiatric comorbidities continue to be under-diagnosed in IBD patients and remain an unresolved issue in the management of these patients. Conclusions: Psychiatric illnesses co-occurring in IBD patients deserve acknowledgment from IBD specialists. These comorbidities highly impact the management of IBD patients and should be studied as an adjunctive therapeutic target.

Cytokines in Spondyloarthritis and Inflammatory Bowel Diseases: From Pathogenesis to Therapeutic Implications.

Spondyloarthritis and inflammatory bowel diseases are chronic immune disorders of the joints and the gut that often coexist in the same patient, increasing the burden of each disorder, worsening patients' quality of life, and influencing therapeutic strategies. Genetic predisposition, environmental triggers, microbiome features, immune cell trafficking, and soluble factors such as cytokines contribute to the pathogenesis of both articular and intestinal inflammation. Most of the molecular targeted biological therapies developed over the last two decades were based on evidence that specific cytokines may be involved in these immune diseases. Despite pro-inflammatory cytokine pathways sharing the pathogenesis of both articular and gut diseases (i.e., tumor necrosis factor and interleukin-23), several other cytokines (i.e., interleukin-17) may be differently involved in the tissue damage process, depending on the specific disease and the organ involved in inflammation, making difficult the identification of a therapeutic plan that is efficacious for both inflammatory manifestations. In this narrative review, we comprehensively summarize the current knowledge on cytokine involvement in spondyloarthritis and inflammatory bowel diseases, underlining similarities and differences among their pathogenetic pathways; finally, we provide an overview of current and potential future treatment strategies to simultaneously target both articular and gut immune disorders.

Artificial intelligence and inflammatory bowel disease: Where are we going?

Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, are chronic and relapsing conditions that pose a growing burden on healthcare systems worldwide. Because of their complex and partly unknown etiology and pathogenesis, the management of ulcerative colitis and Crohn's disease can prove challenging not only from a clinical point of view but also for resource optimization. Artificial intelligence, an umbrella term that encompasses any cognitive function developed by machines for learning or problem solving, and its subsets machine learning and deep learning are becoming ever more essential tools with a plethora of applications in most medical specialties. In this regard gastroenterology is no exception, and due to the importance of endoscopy and imaging numerous clinical studies have been gradually highlighting the relevant role that artificial intelligence has in inflammatory bowel diseases as well. The aim of this review was to summarize the most recent evidence on the use of artificial intelligence in inflammatory bowel diseases in various contexts such as diagnosis, follow-up, treatment, prognosis, cancer surveillance, data collection, and analysis. Moreover, insights into the potential further developments in this field and their effects on future clinical practice were discussed.

Technological advances in inflammatory bowel disease endoscopy and histology.

Accurate disease characterization is the pillar of modern treatment of inflammatory bowel disease (IBD) and endoscopy is the mainstay of disease assessment and colorectal cancer surveillance. Recent technological progress has enhanced and expanded the use of endoscopy in IBD. In particular, numerous artificial intelligence (AI)-powered systems have shown to support human endoscopists' evaluations, improving accuracy and consistency while saving time. Moreover, advanced optical technologies such as endocytoscopy (EC), allowing high magnification in vivo, can bridge endoscopy with histology. Furthermore, molecular imaging, through probe based confocal laser endomicroscopy allows the real-time detection of specific biomarkers on gastrointestinal surface, and could be used to predict therapeutic response, paving the way to precision medicine. In parallel, as the applications of AI spread, computers are positioned to resolve some of the limitations of human histopathology evaluation, such as interobserver variability and inconsistencies in assessment. The aim of this review is to summarize the most promising advances in endoscopic and histologic assessment of IBD.

Gastrointestinal System: COVID-19 and Potential Mechanisms Associated with Coagulopathy.

SARS-CoV-2 is a novel coronavirus that expanded worldwide, generating a pandemic of acute respiratory syndrome called "coronavirus disease 2019" (COVID-19), which resulted in a global health crisis. The spectrum of COVID-19 manifestations ranges from none or mild symptoms to severe respiratory failure associated with systemic manifestations, mostly gastrointestinal symptoms. Hypercoagulability is an important feature of COVID-19 disease, which can potentially influence patients' prognosis. Therefore, gastroenterologists should focus on subjects with concomitant hypercoagulable gastrointestinal disorders as they may display a higher risk of thrombotic complications during SARS-CoV-2 infection. The aim of this review is to summarize the available evidence regarding the interplay of the prothrombotic pathogenetic mechanisms of both COVID-19 and hypercoagulable digestive diseases and the possible clinical implications. We summarized the potential interplay of prothrombotic mechanisms of both COVID-19 and hypercoagulable digestive diseases in the graphical abstract.

Critical Appraisal of Filgotinib in the Treatment of Ulcerative Colitis: Current Evidence and Place in Therapy.

Background and Aims: Patients affected by moderate-to-severe Ulcerative Colitis (UC) demand a challenging management. Small molecules, administrated as oral agents, have the ambition of overcoming the limitations of the biologic agents (ie, parenteral administration, rapidity of action, primary and secondary non-responsiveness). Beyond tofacitinib, a pan-Janus kinase (JAK) inhibitor already approved for the treatment of moderate-to-severe UC, novel more selective molecules like filgotinib are being currently evaluated in randomized clinical trials. We aimed to review the current evidence on filgotinib, a JAK-1 preferential inhibitor, in the treatment of UC and its place in therapy in the current scenario. Methods: PubMed and EMBASE were searched to identify relevant studies: those investigating the efficacy and safety of filgotinib in the treatment of UC patients were included in this narrative review. Results: The current preliminary data have shown that filgotinib is safe and effective in inducing clinical end endoscopic response in both biologic-naïve and biologic-experienced patients with moderate-to-severe UC, also with high inflammatory burden at baseline. In the SELECTION trial, one case of pulmonary embolism occurred with filgotinib 200 mg induction, and three venous thrombosis cases were observed in the placebo maintenance/LTE; the incidence of herpes zoster was ≤1% in all UC treated patients. Filgotinib represents an appealing treatment option for its high selectiveness, route of administration and rapidity of action; cost-effectiveness studies and head-to-head trials are needed to better define its place in therapy.

Sphingosine 1-Phosphate Modulation in Inflammatory Bowel Diseases: Keeping Lymphocytes Out of the Intestine.

Inflammatory bowel diseases (IBDs) are chronic and disabling conditions that, uncontrolled, lead to irreversible bowel damage and associated comorbidities. Despite the new era of biological therapies, IBDs remain not curative. The treatment purpose is to induce endoscopic remission, reduce the progression of the disease and improve the quality of life. Optimal and early treatment could enable the prevention of their complications. Small molecules, administrated as oral agents, have the capacity of overcoming the limitations of biologic agents (i.e., parenteral administration, rapidity of action and primary and secondary non-responsiveness). Of special interest are results from the use of oral sphingosine 1-phosphate (S1P) receptor modulators (ozanimod, etrasimod, fingolimod and laquinimod), based on S1P activities to target lymphocyte recirculation in the mucosa, acting as immunosuppressive agents. Most S1P modulators are reported to be safe and effective in the treatment of both UC and CD. High and satisfactory rates of clinical remission as well as endoscopic improvement and remission can be achieved with these molecules. Safety alarms remain rather low, although the S1P binding to two of its G protein-coupled receptors, 2 and 3 (S1PR2 and S1PR3), may be associated with cardiovascular risks. Cost-effectiveness studies and head-to-head trials are needed to better define their place in therapy. This review summarizes these emerging data published by PubMed and EMBASE databases and from ongoing clinical trials on the safety and efficacy of selectivity of S1P modulators in the treatment of IBD.

Ileal Pouch-Anal Anastomosis and Pouchitis: The Role of the Microbiota in the Pathogenesis and Therapy.

Inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are life-long disorders characterized by the chronic relapsing inflammation of the gastrointestinal tract with the intermittent need for escalation treatment and, eventually, even surgery. The total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical intervention of choice in subjects affected by ulcerative colitis (UC). Although IPAA provides satisfactory functional outcomes, it can be susceptible to some complications, including pouchitis as the most common. Furthermore, 10-20% of the pouchitis may develop into chronic pouchitis. The etiology of pouchitis is mostly unclear. However, the efficacy of antibiotics in pouchitis suggests that the dysbiosis of the IPAA microbiota plays an important role in its pathogenesis. We aimed to review the role of the microbiota in the pathogenesis and as a target therapy in subjects who develop pouchitis after undergoing the surgical intervention of total proctocolectomy with IPAA reconstruction.

Digital single-operator cholangioscopy in diagnostic and therapeutic bilio-pancreatic diseases: A prospective, multicenter study.

BACKGROUND AND AIM: Digital single-operator cholangioscopy (D-SOC) is an endoscopic procedure that is increasingly used for the management of bilio-pancreatic diseases. We aimed to investigate the efficacy and safety of D-SOC for diagnostic and therapeutic indications. METHODS: This is a multicenter, prospective study(January 2016-June 2019) across eighteen tertiary centers. The primary outcome was procedural success of D-SOC. Secondary outcomes were: D-SOC visual assessment and diagnostic yield of SpyBite biopsy in cases of biliary strictures, stone clearance rate in cases of difficult biliary stones, rate of adverse events(AEs) for all indications. RESULTS: D-SOC was performed in 369 patients (201(54,5%) diagnostic and 168(45,5%)therapeutic). Overall, procedural success rate was achieved in 360(97,6%) patients. The sensitivity, specificity, PPV, NPV and accuracy in biliary strictures were: 88,5%, 77,3%, 83,3%, 84,1% and 83,6% for D-SOC visual impression; 80,2%, 92,6%, 95,1%, 72,5% and 84,7% for the SpyBite biopsy, respectively. For difficult biliary stones, complete duct clearance was obtained in 92,1% patients (82,1% in a single session). Overall, AEs occurred in 37(10%) cases.The grade of AEs was mild or moderate for all cases, except one which was fatal. CONCLUSION: D-SOC is effective for diagnostic and therapeutic indications.Most of the AEs were minor and managed conservatively, even though a fatal event has happened that is not negligible and should be considered before using D-SOC.

Endoscopic Surveillance in Inflammatory Bowel Diseases: Selecting a Suitable Technology.

In the treat-to-target era, endoscopy has become the backbone of the assessment of remission, defined as mucosal healing, in inflammatory bowel disease (IBD) patients. Current recommendations indicate that endoscopic procedures should be performed with high-definition white-light endoscopy (HD-WLE), as it guarantees the best possible visualization of the mucosa. With respect to endoscopic surveillance, the preventive strategy for dysplasia and colorectal cancer (CRC) in long-standing IBD, is the use of dye-chromoendoscopy (DCE), which enhances the mucosal pattern of the colonic walls. DCE has been established as the gold standard for dysplasia detection and is at present incorporated in all international guidelines. Over the past years, novel technologies, such as high-definition endoscopic imaging, and optical and digital enhancement tools have revolutionized the quality and level of fine details of vascular and mucosal patterns. These endoscopic images have the ambition to reflect histological changes for suspected neoplastic lesions and inflammation or healing and are emerging as potential alternatives to DCE. Indeed, the comparison of DCE with high-definition imaging is an open issue that deserves further investigation. We aimed to examine and summarize the technical aspects and the current evidence on endoscopic technologies with a specific focus on the surveillance in IBD patients.

Relief of jaundice in malignant biliary obstruction: When should we consider endoscopic ultrasonography-guided hepaticogastrostomy as an option?

BACKGROUND: Since it was first described in 2001, endoscopic ultrasonography-guided biliary drainage (EUS-BD) has emerged as an alternative procedure for achieving an endoscopic internal drainage in case of endoscopic retrograde cholangiopancreatography (ERCP) failure. Biliary drainage can be achieved by either a transduodenal extrahepatic approach through EUS-guided choledochoduodenostomy (EUS-CDS), or a transgastric intrahepatic approach, namely EUS-guided hepaticogastrostomy (EUS-HGS) which already holds a remarkable place in the treatment of patients with malignant biliary obstruction. DATA SOURCES: For this review we did a comprehensive search of PubMed/MEDLINE from inception to May 31, 2021 for papers with a significant sample size (at least 20 patients enrolled) dealing with EUS-HGS. Data on technical success, clinical success and rate of adverse events were collected. RESULTS: A total of 22 studies with different design, comprising 874 patients, were included. Technical success was achieved in about 96% of cases (ranging from 65% to 100%). Clinical success was obtained in almost 91% of cases (ranging from 76% to 100%). Overall rate of adverse events was 19% (ranging from 0% to 35%). Abdominal pain, self-limiting pneumoperitoneum, bile leak, cholangitis, bleeding, perforation and intraperitoneal migration of the stent were the most common. CONCLUSIONS: Despite both safety and efficacy profile, at the moment HGS still remains a challenging procedure at every single step and must therefore be conducted by a very experienced endoscopist in interventional EUS and ERCP procedures, who is able to deal with the possible severe adverse events of this procedure. A rapid introduction in clinical practice of dedicated devices is desiderable.