The Impact of Radiofrequency Ablation on Survival Outcomes and Stent Patency in Patients with Unresectable Cholangiocarcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Endoluminal biliary radiofrequency ablation (RFA) has been proposed as a palliative treatment for patients with malignant biliary obstruction (MBO) in order to improve stent patency and survival. However, the existing data on patients with inoperable extrahepatic cholangiocarcinoma (eCCA) are conflicting. We performed a meta-analysis of randomized trials comparing RFA plus stenting versus stenting alone in patients with inoperable eCCA. We searched for trials published in the PubMed/MEDLINE, Scopus, and Cochrane databases up to November 2023. Data extraction was conducted from published studies, and a quality assessment was carried out in accordance with the guidelines recommended by the Cochrane Collaboration. Hazard ratios (HRs) with 95% CI were estimated from the trials. The primary endpoints of interest were overall survival and stent patency. Out of 275 results, 5 randomized trials and 370 patients were included. While overall survival was not different between the groups (HR 0.62; 95% CI 0.36-1.07; p = 0.09; I2 = 80%;), the subgroup analysis of studies employing plastic stents showed a trend toward better survival in the RFA-treated group (HR 0.42; 95% CI 0.22-0.80; p = 0.009; I2 = 72%). Stent patency was improved in patients receiving RFA (HR 0.64; 95% CI 0.45-0.90; p = 0.01; I2 = 23%). Adverse events were not different between the groups (OR 1.21; 95% CI 0.69-2.12; p = 0.50; I2 = 0%). Despite the promising results, high heterogeneity and potential biases in the included studies suggest the need for further high-quality randomized trials to explore the potential cumulative effects of RFA on CCA treatment outcomes.

Risk Stratification in Primary Biliary Cholangitis.

Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease with a heterogeneous presentation, symptomatology, disease progression, and response to therapy. The current risk stratification assessment, aimed at identifying patients with a higher risk of disease progression, encompasses an in-depth analysis of demographic data, clinical and laboratory findings, antibody profiles, and the evaluation of liver fibrosis using both invasive and noninvasive techniques. Treatment response scores after one year of therapy remain to date a major factor influencing the prognosis of PBC patients. While the initial therapeutic approach with ursodeoxycholic acid (UDCA) is universally applied, new second-line treatment options have recently emerged, with many others under investigation. Consequently, the prevailing one-size-fits-all approach is poised to be supplanted by tailored strategies, ensuring high-risk patients receive the most appropriate treatment regimen from diagnosis. This will require the development of a risk prediction model to assess, at the time of diagnosis, the course, outcome, and response to first and additional treatments of PBC patients. This manuscript provides a comprehensive overview of the current and emerging tools used for risk stratification in PBC and speculates on how these developments might shape the disease landscape in the near future.

Intestinal Bacteremia After Liver Transplantation Is a Risk Factor for Recurrence of Primary Sclerosing Cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic progressive pathological process, related to inflammatory bowel disease and subsequent bacterial translocation. Liver transplantation (LT) is the only curative therapy, but outcomes are compromised by recurrence of PSC (rPSC). The aim of the study was to investigate a potential link between intestinal bacteremia, fucosyltransferase-2 (FUT2), and rPSC after LT. METHODS: LT recipients with PSC (n = 81) or without PSC (n = 271) were analyzed for clinical outcomes and positive bacterial blood cultures. A link between bacteremia and the genetic variant of the FUT2 gene was investigated. RESULTS: The incidence of inflammatory bowel disease was significantly higher in PSC recipients but not associated with rPSC. Bacteremia occurred in 31% of PSC recipients. The incidence of rPSC was 37% and was significantly more common in patients with intestinal bacteremia versus no bacteremia (82% versus 30%; P = 0.003). The nonsecretor polymorphism of the FUT2 gene was identified as a genetic risk factor for both intestinal bacteremia and rPSC. Combined FUT2 genotype and intestinal bacteremia in recipients resulted in the highest risk for rPSC (hazard ratio, 15.3; P < 0.001). CONCLUSIONS: Thus, in this article, we showed that bacterial translocation is associated with rPSC after LT and related to the FUT2 nonsecretor status.

Serological response after anti-SARS-CoV-2 BNT162b2 vaccine in IBD patients on biological therapy: a monocentric case-control study.

BACKGROUND: Inflammatory bowel disease (IBD) patients on biological therapy are receiving vaccines against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). However, it is unclear if IBD therapy could influence the response to this vaccine. In a case-control study, we assessed the antibody profiling after anti-SARS-CoV-2 BNT162b2 vaccine in IBD patients on biological therapy. METHODS: We analyzed seroprevalence and antibody titer, after 14 weeks from the first BNT162b2 vaccine dose, in IBD patients on biological therapy and health care workers (HCWs). In IBD patients, medical history and disease data were recorded. RESULTS: Eighty-two subjects were enrolled in this study. Among them, 40 were IBD patients on biological therapy and 42 were HCWs. All subjects developed an IgG anti-Spike antibody titer above the cut-off. IBD patients on biological therapy developed a lower antibody titer than HCWs (P<0.00001). No differences were reported in patients who received at least one dose of the vaccine within a period of 7 days from the last biological drug administration, compared to all other IBD patients. A difference was found between patients who were on concomitant immunosuppressive therapy and patients on sole biological therapy (P=0.0287). Patients with presence of any sign of disease activity (clinical, endoscopic or laboratory) showed a higher development of antibody titer compared to those in complete disease remission (P=0.0468). CONCLUSIONS: Our data indicate that in IBD patients, treatment with biological therapies do not affect the seroprevalence but leads to a lower antibody titer development after anti-SARS-CoV-2 BNT162b2 vaccine.

Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy.

Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRß induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis. For instance, a better prognosis is associated with IL-33 expression and low stromal IL-6 (whose secretion is stimulated by microRNA). In contrast, a worst prognosis is given by the expression of PDGF-D, podoplanin, SDF-1, α-SMA high expression, and periostin. The maturity phenotype has a prognostic relevance too. New therapeutic strategies involving CAFs are currently under study. Promising results are obtained with anti-PlGF therapy, nintedanib (BIBF1120), navitoclax, IPI-926, resveratrol, and controlled hyperthermia.

Farnesoid X Receptor, Bile Acid Metabolism, and Gut Microbiota.

Obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) are characterized by the concepts of lipo- and glucotoxicity. NAFLD is characterized by the accumulation of different lipidic species within the hepatocytes. Bile acids (BA), derived from cholesterol, and conjugated and stored in the gallbladder, help the absorption/processing of lipids, and modulate host inflammatory responses and gut microbiota (GM) composition. The latter is the new "actor" that links the GI tract and liver in NAFLD pathogenesis. In fact, the discovery and mechanistic characterization of hepatic and intestinal farnesoid X receptor (FXR) shed new light on the gut-liver axis. We conducted a search on the main medical databases for original articles, reviews, meta-analyses of randomized clinical trials, and case series using the following keywords, their acronyms, and their associations: farnesoid X receptor, bile acids metabolism, gut microbiota, dysbiosis, and liver steatosis. Findings on the synthesis, metabolism, and conjugation processes of BAs, and their action on FXR, change the understanding of NAFLD physiopathology. In detail, BAs act as ligands to several FXRs with GM modulation. On the other hand, the BAs pool is modulated by GM, thus, regulating FXRs functioning in the frame of liver fat deposition and fibrosis development. In conclusion, BAs passed from their role of simple lipid absorption and metabolism agents to messengers between the gut and liver, modulated by GM.

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.

Migration rate using fully covered metal stent in anastomotic strictures after liver transplantation: Results from the BASALT study group.

BACKGROUND AND STUDY AIM: The traditional endoscopic therapy of anastomotic strictures (AS) after orthotopic liver transplantation (OLT) is multiple ERCPs with the insertion of an increasing number of plastic stents side-by-side. Fully covered self-expanding metal stents (cSEMS) could be a valuable option to decrease the number of procedures needed or non-responders to plastic stents. This study aims to retrospectively analyse the results of AS endoscopic treatment by cSEMS and to identify any factors associated with its success. PATIENTS AND METHODS: Ninety-one patients (mean age 55.9 ± 7.6 SD; 73 males) from nine Italian transplantation centres, had a cSEMS positioned for post-OLT-AS between 2007 and 2017. Forty-nine (54%) patients were treated with cSEMS as a second-line treatment. RESULTS: All the procedures were successfully performed without immediate complications. After ERCP, adverse events occurred in 11% of cases (2 moderate pancreatitis and 8 cholangitis). In 49 patients (54%), cSEMSs migrated. After cSEMS removal, 46 patients (51%) needed further endoscopic (45 patients) or radiological (1 patient) treatments to solve the AS. Lastly, seven patients underwent surgery. Multivariable stepwise logistic regression showed that cSEMS migration was the only factor associated with further treatments (OR 2.6, 95% CI 1.0-6.6; p value 0.03); cSEMS implantation before 12 months from OLT was associated with stent migration (OR 5.2, 95% CI 1.7-16.0; p value 0.004). CONCLUSIONS: cSEMS appears to be a safe tool to treat AS. cSEMS migration is the main limitation to its routinary implantation and needs to be prevented, probably with the use of new generation anti-migration stents.

Therapeutic effects of dexamethasone-loaded hyaluronan nanogels in the experimental cholestasis.

A major function of the intrahepatic biliary epithelium is bicarbonate excretion in bile. Recent reports indicate that budesonide, a corticosteroid with high receptor affinity and hepatic first pass clearance, increases the efficacy of ursodeoxycholic acid, a choleretic agent, in primary biliary cholangitis patients. We have previously reported that bile ducts isolated from rats treated with dexamethasone or budesonide showed an enhanced activity of the Na+/H+ exchanger isoform 1 (NHE1) and Cl-/HCO3- exchanger protein 2 (AE2) . Increasing the delivery of steroids to the liver may result in three beneficial effects: increase in the choleresis, treatment of the autoimmune or inflammatory liver injury and reduction of steroids' systemic harmful effects. In this study, the steroid dexamethasone was loaded into nanohydrogels (or nanogels, NHs), in order to investigate corticosteroid-induced increased activities of transport processes driving bicarbonate excretion in the biliary epithelium (NHE-1 isoform) and to evaluate the effects of dexamethasone-loaded NHs (NHs/dex) on liver injury induced by experimental cholestatis. Our results showed that NHs and NHs/dex do not reduce cell viability in vitro in human cholangiocyte cell lines. Primary and immortalized human cholangiocytes treated with NHs/dex show an increase in the functional marker expression of NHE1 cholangiocytes compared to control groups. A mouse model of cholangiopathy treated with NHs/dex shows a reduction in markers of hepatocellular injury compared to control groups (NHs, dex, or sham group). In conclusion, we believe that the NHs/dex formulation is a suitable candidate to be investigated in preclinical models of cholangiopathies.

Future challenges in gastroenterology and hepatology, between innovations and unmet needs: A SIGE Young Editorial Board's perspective.

Gastroenterology, Digestive Endoscopy and Hepatology have faced significant improvements in terms of diagnosis and therapy in the last decades. However, many fields still remain poorly explored, and many questions unanswered. Moreover, basic-science, as well as translational and clinical discoveries, together with technology advancement will determine further steps toward a better, refined care for many gastroenterological disorders in the future. Therefore, the Young Investigators of the Italian Society of Gastroenterology (SIGE) joined together, offering a perspective on major future innovations in some hot clinical topics in Gastroenterology, Endoscopy, and Hepatology, as well as the current pitfalls and the grey zones.

Gastrointestinal Complications after Allogeneic Hematopoietic Stem Cell Transplant: A Multidisciplinary Approach with Early Endoscopic Evaluation.

Gastrointestinal complications (GICs) represent the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Differential diagnosis of GICs is of paramount importance since early and reliable identification of graft-versus-host disease (GVHD) is essential for a correct management of the patients. The aim of the present retrospective study was to evaluate the occurrence of GICs after allo-HSCT and to assess the diagnostic performance of a quick endoscopic and histological assessment in the differential diagnosis between GVHD and other GI conditions. Between January 2015 and August 2019, 122 consecutive patients receiving an allo-HSCT were managed by an interdisciplinary team, supported by a dedicated endoscopic service. Clinical, therapeutic, endoscopic and histological data were analyzed for each patient. Collectively, 94 of the patients developed GICs (77%). A moderate-severe mucositis was the most frequent complication, occurring in 79 patients (84%). Acute GI-GVHD was diagnosed in 35 patients (37% of whom with GICs) and 19 of them with a moderate-severe grade. Infective acute colitis developed in eight patients, mainly due to Clostridium difficile (CD) and Cytomegalovirus infections (8.5%). Rectal biopsy showed the highest sensitivity and specificity (80% and 100%, respectively). However, when biopsy procedures were guided by symptoms and performed on apparently intact mucosa, upper histology also provided a high negative predictive value (80%). Our multidisciplinary approach with a quick endoscopic/histologic investigation in the patients receiving an allo-HSCT and who suffered GICs could improve diagnostic and therapeutic management in this challenging setting.

Anticoagulation and Vessel Recanalization in Cirrhotic Patients with Splanchnic Vein Thrombosis: A Multidisciplinary "Real Life" Experience.

BACKGROUND AND AIM: Splanchnic vein thrombosis (SVT) is a potentially life-threatening complication of liver cirrhosis. This study aimed to evaluate the impact of a multi-disciplinary approach and early anticoagulation therapy (AT) on bleeding/thrombotic events, recanalization rates and outcome of cirrhotic patients with SVT. METHODS: This is a single-center, registry-based cohort study. Over 17 years, 149 SVT patients were enrolled and prospectively evaluated. Regarding cirrhotic-SVT, a pre-specified algorithm, guiding initial posology of AT and follow-up visits schedule, was performed. Major bleeding (MB), thrombotic events, functional liver scores and all cause-mortality were investigated. Efficacy of AT was evaluated by radiological imaging. RESULTS: In cirrhotic-SVT, the incidence rate of MB was 8.4 per 100 patient-year (95% CI, 3.83-15.97), while the incidence rate of thrombosis was 5.6 per 100 patient-year (95% CI, 2.05-12.2). In incidental SVT treated with AT, MB incidence was 6.5 per 100 patient-year (95% CI: 2.8-12.82), while in symptomatic SVT was 2.2 per 100 patient-year (95% CI: 0.25-8.02). All thrombotic recurrences occurred in incidental SVT (7.7 per 100 patient-years; 95% CI, 3.71-14.26). Overall survival was significantly higher in patients who had at least a partial recanalization (p < 0.01) and partial/total recanalization was independently associated with improved MELD score at multivariate analysis (HR 2.62, 95% CI 1.1-6.47, p = 0.03). CONCLUSION: In cirrhotic SVT patients, partial or total resolution of thrombosis ameliorates liver function and is associated with higher overall survival. A multidisciplinary approach together with radiological follow-up at pre-fixed time improves patient selection and monitoring.

Involvement of Autophagy in Ageing and Chronic Cholestatic Diseases.

Autophagy is a "housekeeping" lysosomal degradation process involved in numerous physiological and pathological processes in all eukaryotic cells. The dysregulation of hepatic autophagy has been described in several conditions, from obesity to diabetes and cholestatic disease. We review the role of autophagy, focusing on age-related cholestatic diseases, and discuss its therapeutic potential and the molecular targets identified to date. The accumulation of toxic BAs is the main cause of cell damage in cholestasis patients. BAs and their receptor, FXR, have been implicated in the regulation of hepatic autophagy. The mechanisms by which cholestasis induces liver damage include mitochondrial dysfunction, oxidative stress and ER stress, which lead to cell death and ultimately to liver fibrosis as a compensatory mechanism to reduce the damage. The stimulation of autophagy seems to ameliorate the liver damage. Autophagic activity decreases with age in several species, whereas its basic extends lifespan in animals, suggesting that it is one of the convergent mechanisms of several longevity pathways. No strategies aimed at inducing autophagy have yet been tested in cholestasis patients. However, its stimulation can be viewed as a novel therapeutic strategy that may reduce ageing-dependent liver deterioration and also mitigate hepatic steatosis.

Role of autophagy in cholangiocarcinoma: Pathophysiology and implications for therapy.

Cholangiocarcinoma (CCA) is a malignant tumour of the biliary system that originates from the neoplastic transformation of cholangiocytes. CCA is characterized by late diagnosis and poor outcome, with surgery considered as the last option for management. Autophagy is a physiological lysosomal degradation process, essential for cellular homeostasis and ubiquitous in all eukaryotic cells. Several studies have reported a potential involvement of autophagy in cancer, but it remains unclear whether activation of this process represents a survival mechanism of cancer cells. In the present review, we examine the autophagic process and summarize the current knowledge about the involvement of autophagy in the progression of cancer. The link between autophagy and chemoresistance and the use of autophagic markers in diagnosis are also considered in detail. Preliminary evidence shows that the combination of autophagy modulators (activators or inhibitors) with conventional chemotherapeutic agents offers a possible treatment option against signalling pathways that are hyperactivated or altered in CCA. In vitro evidence suggests that combination of chemotherapy agents, such as cisplatin, under activation or inhibition of autophagic processes, in two different CCA cell lines, may improve chemosensitivity and reduce cell survival, respectively. A deeper understanding of these pathways, in both cancer and non-cancer cells, could unveil possible therapeutic targets to treat CCA patients.

The Management of Cholestatic Liver Diseases: Current Therapies and Emerging New Possibilities.

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two chronic cholestatic liver diseases affecting bile ducts that may progress to biliary cirrhosis. In the past few years, the increasing knowledge in the pathogenesis of both diseases led to a growing number of clinical trials and possible new targets for therapy. In this review, we provide an update on the treatments in clinical use and summarize the new drugs in trials for PBC and PSC patients. Farnesoid X Receptor (FXR) agonists and Pan-Peroxisome Proliferator-Activated Receptor (PPAR) agonists are the most promising agents and have shown promising results in both PBC and PSC. Fibroblast Growth Factor 19 (FGF19) analogues also showed good results, especially in PBC, while, although PBC and PSC are autoimmune diseases, immunosuppressive drugs had disappointing effects. Since the gut microbiome could have a potential role in the pathogenesis of PSC, recent research focused on molecules that could change the microbiome, with good results. The near future of the medical management of these diseases may include new treatments or a combination of multiple drugs targeting different signaling pathways at different stages of the diseases.

Gastrointestinal disorders as immune-related adverse events.

Immune checkpoint inhibitors, such as cytotoxic T-lymphocyte antigen 4 inhibitors, programmed cell death 1 inhibitors and programmed cell death-ligand 1 inhibitors, have recently emerged as novel drugs in the anti-cancer therapy. Their use in different types of advanced cancer has shown good results and an increase in survival rates. However, immune-related adverse events (irAEs) are frequent and often require special care. IrAEs may affect all the organs, but they are most commonly seen in skin, lungs, endocrine glands and in the gastrointestinal tract where small bowel, colon, the liver and/or the pancreas can be involved. Despite being usually mild and self-resolving, irAEs may present in severe and life-threatening forms, causing the withdrawal of anti-cancer therapy. IrAEs, therefore, represent a challenging condition to manage that often requires the cooperation between the oncologists and the gastroenterologists in order to identify and treat them adequately.

HDL cholesterol protects from liver injury in mice with intestinal specific LXRα activation.

BACKGROUND AND AIMS: Liver X receptors (LXRs) exert anti-inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects. METHODS: Mice with intestinal constitutive LXRα activation (iVP16-LXRα) were exposed to intraperitoneal injection of carbon tetrachloride (CCl4 ) for 8 weeks, and in vitro cell models were used to evaluate the beneficial effect of high-density lipoproteins (HDL). RESULTS: After CCl4 treatment, the iVP16-LXRα phenotype showed reduced M1 macrophage infiltration, increased expression M2 macrophage markers, and lower expression of hepatic pro-inflammatory genes. This anti-inflammatory effect in the liver was also associated with decreased expression of hepatic oxidative stress genes and reduced expression of fibrosis markers. iVP16-LXRα exhibited increased reverse cholesterol transport in the gut by ABCA1 expression and consequent enhancement of the levels of circulating HDL and their receptor SRB1 in the liver. No hepatic steatosis development was observed in iVP16-LXRα. In vitro, HDL induced a shift from M1 to M2 phenotype of LPS-stimulated Kupffer cells, decreased TNFα-induced oxidative stress in hepatocytes and reduced NF-kB activity in both cells. SRB1 silencing reduced TNFα gene expression in LPS-stimulated KCs, and NOX-1 and IL-6 in HepG2. CONCLUSIONS: Intestinal activation of LXRα modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy.

Gut-Liver Axis and Inflammasome Activation in Cholangiocyte Pathophysiology.

The Nlrp3 inflammasome is a multiprotein complex activated by a number of bacterial products or danger signals and is involved in the regulation of inflammatory processes through caspase-1 activation. The Nlrp3 is expressed in immune cells but also in hepatocytes and cholangiocytes, where it appears to be involved in regulation of biliary damage, epithelial barrier integrity and development of fibrosis. Activation of the pathways of innate immunity is crucial in the pathophysiology of hepatobiliary diseases, given the strong link between the gut and the liver. The liver secretes bile acids, which influence the bacterial composition of the gut microbiota and, in turn, are heavily modified by microbial metabolism. Alterations of this balance, as for the development of dysbiosis, may deeply influence the composition of the bacterial products that reach the liver and are able to activate a number of intracellular pathways. This alteration may be particularly important in the pathogenesis of cholangiopathies and, in particular, of primary sclerosing cholangitis, given its strong association with inflammatory bowel disease. In the present review, we summarize current knowledge on the gut-liver axis in cholangiopathies and discuss the role of Nlrp3 inflammasome activation in cholestatic conditions.

New biliary and pancreatic biodegradable stent placement: a single-center, prospective, pilot study (with video).

BACKGROUND AND AIMS: In recent years, the feasibility and safety of endoscopic placement of different biodegradable biliary stents have been investigated. New, helicoidally shaped, biliary and pancreatic biodegradable stents have been developed for endoscopic use. Stents are provided in different sizes and with 3 expected speeds of degradation: slow (11 weeks), medium (20 days), and fast (12 days). The aim of this study was to evaluate degradation time, technical outcomes, and safety of these stents. METHODS: This was a single-center, prospective, pilot study (August 2018 to January 2019) of consecutive patients with indication for biliary or pancreatic plastic stent positioning during ERCP. The primary outcome was the evaluation of degradation time of the stents, which was controlled by abdominal radiograph. Secondary outcomes were the evaluation of specific stent-related technical features (loadability, pushability, and fluoroscopic visibility) as compared with commonly used plastic stents and adverse events (AEs). RESULTS: Thirty-eight patients (11 women [28.9%]; median age, 68.05 ± 10.74 years) who received 53 biodegradable stents (34 [64.2%] biliary and 19 [35.8%] pancreatic stents) were enrolled in the study. Thirty-five (66%) slow-degrading stents, 6 (11.3%) medium-degrading stents, and 12 (22.6%) fast-degrading stents were used. At time 1, partial degradation of the stents was present in 48 cases (90.6%). Five stents (9.4%) prematurely migrated. At the subsequent time 2 evaluation, complete degradation occurred in 100% of cases. Stent loadability was defined as excellent in all cases. Pushability of the stent was scored as excellent in 48 cases (90.5%), good in 4 cases (7.5%), and fair in 1 case (1.9%). Fluoroscopic visualization was excellent in 11 cases (20.8%), good in 39 cases (73.6%), and fair in 3 (5.6%). Only 1 AE of mild post-ERCP pancreatitis occurred. CONCLUSIONS: The results of our study suggest that the biodegradation of the new biliary and pancreatic stents is reliable and in line with expected times and technically successful in a variety of indications. Further randomized multicenter studies are required to validate our preliminary findings. (Clinical trial registration number: NCT03767166.).

Aging and the Biological Response to Liver Injury.

Interest in understanding the aging process has recently risen in the scientific community. Aging, commonly defined as the functional decline in the function of organs and tissues, is indeed the major risk factor for the development of many chronic diseases, such as cardiovascular diseases, pathologies of nervous system, or cancer. To date, the influence of aging in the pathophysiology of liver and biliary diseases is not fully understood. Although liver cells have a high regenerative capacity, hepatocytes and cholangiocytes undergo extensive molecular changes in response to aging. Following time-dependent damage induced by aging, liver cells initially activate compensatory mechanisms that, if hyperstimulated, may lead to the decline of regenerative capacity and the development of pathologies. A deeper understanding of molecular aging has undoubtedly the potential to improve the clinical management of patients, possibly unveiling new pathways for selective drug treatment.