Search

In counteracting highly infectious and disruptive respiratory diseases such as COVID-19, vaccination remains the primary and safest way to prevent disease, reduce the severity of illness, and save lives. Unfortunately, vaccination is often not the first intervention deployed for a new pandemic, as it takes time to develop and test vaccines, and confirmation of safety requires a period of observation after vaccination to detect potential late-onset vaccine-associated adverse events. In the meantime, nonpharmacologic public health interventions such as mask-wearing and social distancing can provide some degree of protection. As climate change, with its environmental impacts on pathogen evolution and international mobility continue to rise, highly infectious respiratory diseases will likely emerge more frequently and their impact is expected to be substantial. How quickly a safe and efficacious vaccine can be deployed against rising infectious respiratory diseases may be the most important challenge that humanity will face in the near future. While some organizations are engaged in addressing the World Health Organization's "blueprint for priority diseases", the lack of worldwide preparedness, and the uncertainty around universal vaccine availability, remain major concerns. We therefore propose the establishment of an international candidate vaccine pool repository for potential respiratory diseases, supported by multiple stakeholders and countries that contribute facilities, technologies, and other medical and financial resources. The types and categories of candidate vaccines can be determined based on information from previous pandemics and epidemics. Each participant country or region can focus on developing one or a few vaccine types or categories, together covering most if not all possible potential infectious diseases. The safety of these vaccines can be tested using animal models. Information for effective candidates that can be potentially applied to humans will then be shared across all participants. When a new pandemic arises, these pre-selected and tested vaccines can be quickly tested in RCTs for human populations., Competing Interests: Peter Hotez is a co-inventor of a COVID-19 recombinant protein vaccine technology owned by Baylor College of Medicine (BCM) that was recently licensed by BCM non-exclusively and with no patent restrictions to several companies committed to advance vaccines for low- and middle-income countries. The co-inventors have no involvement in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries that result in a commercial license, a share of any royalty income, according to BCM policy. Jerome H. Kim services as the consultant for SK bioscience and Moderna. Other authors declare no competing financial interests.

Focal active colitis (FAC) is described as a histolopathological term indicating the isolated finding of focal neutrophil infiltration in the colonic crypts. Currently, there exist numerous debates regarding the clinical significance of diagnosing FAC, which may or may not have clinical relevance as it is frequently detected in colorectal biopsies without any other microscopic abnormalities. The objective of this narrative review is to provide an overview of the available evidence concerning the clinical implications of FAC, both in the adult population (among five studies available in the scientific literature) and in the pediatric context (based on two available studies).

Introduction: Individuals with chronic pancreatitis (CP) are at increased risk for nutritional complications during their clinical course. We appraised the literature to provide updated estimates of the prevalence and predictors of osteoporosis, osteopenia, and osteopathy in CP using a systematic review and meta-analysis., Methods: Search strategies were developed for major databases from inception through October 2021. Outcomes of interest included rates of osteopenia and osteoporosis based on dual-energy X-ray absorptiometry scans and risk factors. A random-effects model was used for analysis, and results were expressed as pooled cumulative rates along with 95% confidence interval (CI)., Results: From an initial total of 1,704 identified articles, we ultimately selected 17 studies that involved 1,659 subjects (n = 1,067 men) with CP. The pooled rate of osteopathy was 58% (95% CI: 49%-67%; P < 0.001; I 2 = 91.8%). The pooled rate of osteoporosis was 18% (95% CI: 12%-23%; P < 0.001; I 2 = 86.3%), and the pooled rate of osteopenia was 39% (95% CI: 31%-48%; P < 0.001; I 2 = 91.53%). In the systematic review, factors associated with decreased bone mineral density included smoking, alcohol consumption, older age, female sex, low body mass index, decreased vitamins D and K, and fecal elastase levels., Discussion: Patients with CP have high rates of osteopathy when assessed with dual-energy X-ray absorptiometry imaging. Additional studies with longitudinal follow-up are needed to understand the observed heterogeneity, the cumulative burden of disease, and rate of bone loss in CP., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Artificial intelligence (AI) in gastrointestinal endoscopy includes systems designed to interpret medical images and increase sensitivity during examination. This may be a promising solution to human biases and may provide support during diagnostic endoscopy., Areas Covered: This review aims to summarize and evaluate data supporting AI technologies in lower endoscopy, addressing their effectiveness, limitations, and future perspectives., Expert Opinion: Computer-aided detection (CADe) systems have been studied with promising results, allowing for an increase in adenoma detection rate (ADR), adenoma per colonoscopy (APC), and a reduction in adenoma miss rate (AMR). This may lead to an increase in the sensitivity of endoscopic examinations and a reduction in the risk of interval-colorectal cancer. In addition, computer-aided characterization (CADx) has also been implemented, aiming to distinguish adenomatous and non-adenomatous lesions through real-time assessment using advanced endoscopic imaging techniques. Moreover, computer-aided quality (CADq) systems have been developed with the aim of standardizing quality measures in colonoscopy (e.g. withdrawal time and adequacy of bowel cleansing) both to improve the quality of examinations and set a reference standard for randomized controlled trials.

Introduction: The burden of post-COVID-19 functional dyspepsia (FD) and irritable bowel syndrome (IBS) remains unclear. The aim of this meta-analysis was to estimate the rate of post-COVID-19 FD and IBS., Methods: MEDLINE, Scopus and Embase were searched through 17 December 2022. Studies reporting the incidence of FD and/or IBS in COVID-19 survivors and controls (without COVID-19), when available, according to the Rome criteria, were included. Estimated incidence with 95% confidence intervals (CI) was pooled. The odds ratio (OR) with 95% confidence intervals (CI) was pooled; heterogeneity was expressed as I 2 ., Results: Ten studies met the inclusion criteria and were included in the analysis. Overall, four studies including 1199 COVID-19 patients were considered for FD. Post-COVID-19 FD was reported by 72 patients (4%, 95% CI: 3%-5% and I 2 0%). The pooled OR for FD development (three studies) in post-COVID-19 patients compared to controls was 8.07 (95% CI: 0.84-77.87, p = 0.071 and I 2  = 67.9%). Overall, 10 studies including 2763 COVID-19 patients were considered for IBS. Post-COVID-19 IBS was reported by 195 patients (12%, 95% CI: 8%-16%, I 2 95.6% and Egger's p = 0.002 test). The pooled OR for IBS development (four studies) in COVID-19 patients compared to controls was 6.27 (95% CI: 0.88-44.76, p = 0.067 and I 2  = 81.4%); considering only studies with a prospective COVID-19 cohort (three studies), the pooled OR was 12.92 (95% CI: 3.58-46.60, p < 0.001 and I 2  = 0%)., Conclusions: COVID-19 survivors were found to be at risk for IBS development compared to controls. No definitive data are available for FD., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Sarcopenia has been associated with poor prognosis in chronic diseases., Aims: To investigate the role of sarcopenia in predicting clinical and endoscopic outcomes in patients with Crohn's disease (CD)., Methods: Consecutive CD patients who started biologics between 2014 and 2020 and underwent abdominal magnetic resonance or computed tomography within 6 months from the beginning of the biological therapy were enroled. Sarcopenia was defined as Psoas Muscle Index (PMI) lower than 5.4 cm²/m² (men) and 3.56 cm²/m² (women). Univariate and multivariate analyses were used to evaluate whether sarcopenia could predict steroid-free clinical remission (SFCR), endoscopic remission (ER), hospitalisation and surgery after 12 months of therapy., Results: 358 patients were included. Sarcopenia was found in 18.2% of patients, and it was associated with a lower rate of ER (14.8% vs 47.7%; p = 0.002) after 12 months of therapy, while it was not associated with SFCR (65.1% vs 70.1%; p = 0.435), hospitalisation (9.2% vs 7.8%; p = 0.801) and surgery (3.1% vs 6.1%; p = 0.549). Sarcopenia was identified as a predictor of lack of ER (odds ratio [OR]=5.2; p = 0.006), as well as smoking (OR=2.5; p = 0.028) and perianal disease (OR=2.6; p = 0.020)., Conclusion: Sarcopenia is a negative prognostic factor for ER in CD patients treated with biologics., Competing Interests: Conflict of interest S.R. served as an advisory board member for AbbVie and MSD Pharmaceuticals, and received lecture grants from AbbVie, Janssen, MSD, and Takeda Pharmaceuticals. F.S.M. served as an advisory board member and/or received lecture grants from AbbVie, Biogen, Galapagos, Janssen, MSD, Pfizer, Samsung Bioepis, and Takeda Pharmaceuticals. A.O served as an advisory board member for AbbVie, Galapagos, MSD, Janssen, Pfizer, Takeda Pharmaceuticals, and received lecture grants from AbbVie, MSD, Sofar, Chiesi, Janssen, Pfizer, and Takeda Pharmaceuticals. All other authors have no conflict of interest to declare., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: In clinical practice, standard endoscopic treatment of biliary stones fails in up to 10% of patients, and more invasive procedures such as percutaneous trans-hepatic interventions or surgery might become necessary. The aim of this multicenter retrospective study, based on prospectively-collected data, was to evaluate both the efficacy and the safety of digital-single operator cholangioscopy (D-SOC) to treat difficult biliary stones in cases with a previous failure of conventional endoscopic methods., Methods: Only patients with a previous failure of endoscopic standard treatment and a D-SOC-based biliary stone treatment using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) were included. The primary endpoint was to evaluate the stone clearance rate per procedure and per patient., Results: Out of 1258 ERCP performed at our centers, 31 cholangioscopes in 21 patients were solely performed for the treatment of difficult biliary stones using EHL or LL. A complete biliary stone removal was achieved in 67.7% (21/31) of all procedures including initial and repeated examinations, while in 35.4% (11/31) of all procedures an incomplete removal was accomplished of which 36.3% had a partial stone removal. In 22 procedures EHL was adopted as techniques to fragment and remove biliary stones, while in 9 procedures LL was used. In both the techniques, the complete stone removal rate and the incomplete stone removal rate were similar (75% vs. 77.7%, P>0.05). Furthermore, the success rate of digital D-SOC to treat difficult biliary stones was assessed per patient: overall, 100% of patients with difficult biliary stones were successfully treated using D-SOC. Only one patient experienced mild cholangitis classified ad mild adverse event following ASGE (American Society of Gastrointestinal Endoscopy) lexicon., Conclusions: Our data indicate that digital D-SOC assisted biliary stone treatment is highly efficient for the treatment of difficult biliary stones even in such patients in whom previous conventional endoscopic methods to treat biliary stones have failed. Therefore, D-SOC might be considered the new standard of care for these patients, being both, effective and safe.

Background and Aims: The introduction of motorized spiral enteroscopy (mSE) into clinical practice holds diagnostic and therapeutic potential for small-bowel investigations. This systematic review and meta-analysis aims to evaluate the performance of this modality in diagnosing and treating small-bowel lesions., Methods: A systematic search of MEDLINE, Cochrane, and ClinicalTrials.gov databases were performed through September 2022. The primary outcome was diagnostic success, defined as the identification of a lesion relative to the indication. Secondary outcomes were successful therapeutic manipulation, total enteroscopy rate (examination from the duodenojejunal flexion to the cecum), technical success (passage from the ligament of Treitz or ileocecal valve for anterograde and retrograde approach, respectively), and adverse event rates. We performed meta-analyses using a random-effects model, and the results are reported as percentages with 95% confidence intervals (CIs)., Results: From 2016 to 2022, 9 studies (959 patients; 42% women; mean age >45 years; 474 patients [49.4%] investigated for mid-GI bleeding/anemia) were considered eligible and included in analysis. The diagnostic success rate of mSE was 78% (95% CI, 72-84; I 2  = 78.3%). Considering secondary outcomes, total enteroscopy was attempted in 460 cases and completed with a rate of 51% (95% CI, 30-72; I 2  = 96.2%), whereas therapeutic interventions were successful in 98% of cases (95% CI, 96-100; I 2  = 79.8%) where attempted. Technical success rates were 96% (95% CI, 94-97; I 2  = 1.5%) for anterograde and 97% (95% CI, 94-100; I 2  = 38.6%) for retrograde approaches, respectively. Finally, the incidence of adverse events was 17% (95% CI, 13-21; I 2  = 65.1%), albeit most were minor adverse events (16%; 95% CI, 11-20; I 2  = 67.2%) versus major adverse events (1%; 95% CI, 0-1; I 2  = 0%)., Conclusions: mSE provides high rates of diagnostic and therapeutic success with a low prevalence of severe adverse events., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Competing Interests: We declare no competing interests.

Background and study aims Pancreatic necrosis is an independent predictor of morbidity and mortality among patients with acute pancreatitis. We compared the safety and outcomes of three techniques including endoscopic necrosectomy, fluoroscopy-guided percutaneous necrosectomy by an interventional radiologist, and surgical necrosectomy. Patients and methods Using the Nationwide Readmissions Database, we identified hospitalized patients who underwent pancreatic necrosectomy from 2016 to 2019. They were identified using the International Classification of Diseases, 10th Revision, Procedure Coding System. Results: Of the 2,281 patients meeting the selection criteria, the method of pancreatic necrosectomy was as follows: endoscopy (n = 672), percutaneous (n = 1,338), and surgery (n = 271). Compared to surgery, the rate of mortality was lowest for endoscopy (hazard ratio (HR) 0.27; 95 % CI 0.08-0.90; P  = 0.033) followed by percutaneous (HR 0.44; 95 % CI, 0.20-0.98; P  = 0.045). Endoscopy was associated with less post-procedure bleeding compared to percutaneous and surgical necrosectomy ( P  < 0.001), as well as lower rates of post-procedure renal failure ( P  < 0.001) and respiratory failure ( P  = 0.002). Endoscopy was associated with average shorter lengths of stay and total hospital costs when compared with percutaneous and surgical approaches, respectively (20.1 vs 25.8 vs 38.3 days; P  < 0.001) and ($ 57K vs $ 76K vs $ 123K; P  < 0.001). Conclusions Endoscopic necrosectomy is associated with significantly lower risk of inpatient mortality, adverse events, length of stay, and cost when compared to percutaneous and surgical approaches., Competing Interests: Competing interests Dr. Douglas G. Adler is a consultant for Boston Scientific and Micro Tech. All other authors have no relevant conflict of interests., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Adequate bowel cleansing is critical for a high-quality colonoscopy because it affects diagnostic accuracy and adenoma detection. Nevertheless, almost a quarter of procedures are still carried out with suboptimal preparation, resulting in longer procedure times, higher risk of complications, and higher likelihood of missing lesions. Current guidelines recommend high-volume or low-volume polyethylene glycol (PEG)/non-PEG-based split-dose regimens. In patients who have had insufficient bowel cleansing, the colonoscopy should be repeated the same day or the next day with additional bowel cleansing as a salvage option. A strategy that includes a prolonged low-fiber diet, a split preparation regimen, and a colonoscopy within 5 h of the end of preparation may increase cleansing success rates in the elderly. Furthermore, even though no specific product is specifically recommended in the other cases for difficult-to-prepare patients, clinical evidence suggests that 1-L PEG plus ascorbic acid preparation are associated with higher cleansing success in hospitalized and inflammatory bowel disease patients. Patients with severe renal insufficiency (creatinine clearance < 30 mL/min) should be prepared with isotonic high volume PEG solutions. Few data on cirrhotic patients are currently available, and no trials have been conducted in this population. An accurate characterization of procedural and patient variables may lead to a more personalized approach to bowel preparation, especially in patients undergoing resection of left colon lesions, where intestinal preparation has a poor outcome. The purpose of this review was to summarize the evidence on the risk factors influencing the quality of bowel cleansing in difficult-to-prepare patients, as well as strategies to improve colonoscopy preparation in these patients., Competing Interests: Conflict-of-interest statement: All authors have no proprietary, financial, professional, or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of this manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Data from the first wave of the coronavirus disease 2019 (COVID-19) pandemic suggested that patients with inflammatory bowel disease (IBD) are not at higher risk of being infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and that a worse prognosis is not associated with immunomodulatory drugs, with the possible exception of systemic steroids., Methods: This retrospective, observational study included consecutive IBD patients from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) cohort who had a SARS-CoV-2 infection diagnosis (polymerase chain reaction-confirmed presence of the viral genome in a nasopharyngeal swab) during the second COVID-19 pandemic wave (September 2020 to December 2020). Data regarding demographics, IBD features and treatments, and comorbidities were analyzed in correlation with COVID-19 clinical outcomes., Results: Data on 122 patients (mean age, 43.9 ± 16.7 years; males, 50.0%; Crohn's disease, 62.3%; ulcerative colitis, 37.7%) were reported. Twelve patients developed COVID-19-related pneumonia (9.8%), 4 (3.3%) required respiratory assistance (nonmechanical ventilation or orotracheal intubation), and 4 died (case fatality rate, 3.3%). In a multivariable analysis, age (odds ratio [OR], 1.034; 95% CI, 1.006-1.147; P = .032) and severe IBD activity (OR, 13.465; 95% CI, 1.104-164.182; P = .042) were independent predictors of COVID-19-related pneumonia, while severe IBD activity (OR, 15.359; 95% CI, 1.320-178.677; P = .030) was the only independent predictor of severe COVID-19, a composite endpoint defined as the need for respiratory assistance or death. A trend towards a protective role of tumor necrosis factor α inhibitors on pneumonia development was reported (P = .076)., Conclusions: In this cohort of patients with IBD and SARS-CoV-2 infection, severe IBD activity was the only independent risk factor for severe COVID-19., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS). Methods: Data derived from a multicenter series of 313 HCC patients treated with lenvatinib between 2019 and 2022 were analyzed. Actuarial survival estimates were computed using the Kaplan−Meier method and compared with the log-rank test. We performed an event-based counterfactual mediation analysis to estimate direct (chronic inflammation and immunosuppression), indirect (tobacco smoking, alcohol use, illicit drug abuse with injections), and the total effect of viral etiology on OS. Results were expressed as hazard ratio (HR) and 95% CI. Results: Median OS was 21 months (95% CI: 20−23) in the group with other etiologies and 15 months (14−16) in the group with viral etiology (p < 0.0001). The total effect of viral etiology was associated with OS (HR 2.76, 1.32−5.21), and it was mainly explained by the pure direct effect of viral etiology (HR 2.74, 1.15−4.45). By contrast, its total indirect effect was not associated with poorer survival (HR 1.05, 0.82−2.13). These results were confirmed when considering tobacco, alcohol consumption, or injection drug abuse as potential mediators. Median progression-free survival was 9 months (8−10) in patients with other etiologies and 6 months (5−7) in patients with viral etiology (p < 0.0001). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Patients affected by HCC with nonviral etiology treated with lenvatinib exhibit longer survival than those with viral etiology. This finding may have relevance in the treatment decision-making process.

Factors affecting the quality of bowel preparation for colonoscopy in the elderly are not fully known, and current guidelines provide no specific recommendations. This study aimed to assess the difference in bowel cleansing in young and elderly patients and evaluate predictors of bowel cleansing in the elderly. We retrospectively reviewed a prospective cohort of 1289 patients performing colonoscopy after a 1-, 2-, or 4-L PEG-based preparation. All 1289 were included in the analysis. Overall, 44.6% of patients were aged ≥65 years. Cleansing success (CS) was achieved in 77.3% and 70.3% of patients aged <65 years and ≥65 years, respectively. At multivariable analysis, split regimen (OR = 2.43, 95% CI = 1.34−4.38; p = 0.003), adequate cleansing at previous colonoscopy (OR = 2.29, 95% CI = 1.14−4.73; p = 0.02), tolerability score (OR = 1.29, 95% CI = 1.16−1.44; p < 0.001), a low-fiber diet for at least 3 days (OR = 2.45, 95% CI = 1.42−4.24; p = 0.001), and colonoscopy within 5 h after the end of preparation (OR = 2.67, 95% CI = 1.28−5.56; p = 0.008) were independently associated with CS in the elderly. Combining a low-fiber diet for at least 3 days, split preparation, and colonoscopy within 5 h allowed a CS rate above 90% and should always be encouraged. A 1-L PEG-ASC preparation was also associated with greater high-quality cleansing of the right colon and may be preferred.

Background: There is currently scarce knowledge about markers of early therapeutic response in patients with inflammatory bowel disease (IBD) treated with biologics. The aim of this study was to evaluate the role of fecal calprotectin (FC) as an early predictor of mucosal healing and clinical remission., Methods: Data from a multicenter series of 172 IBD patients treated with biologics between 2017 and 2020 were analyzed. Treatment outcomes were mucosal healing and clinical remission assessed at 2 years. FC levels were assessed at 14 weeks (post-induction), at 6 months, and yearly. The receiver operating characteristic (ROC) curve analysis was performed to calculate the best cut-off in % change of FC levels between post-induction and baseline predicting treatment outcomes. Sensitivity, specificity, and accuracy for several post-induction FC cut-off points were also calculated., Results: At 2 years, mucosal healing was noted in 77 patients (44.7%), of whom were 41 Crohn's disease (CD) and 36 ulcerative colitis (UC) patients, whereas 106 patients experienced clinical remission (61.6%), of whom were 59 CD and 47 UC patients. Both baseline and post-induction FC levels were significantly higher in non-responders as compared to responders. On the other hand, FC decrease was less pronounced in non-responders. Similar results were observed in all subgroups, namely according to disease (CD vs. UC), or treatment used (TNF-inhibitors vs. vedolizumab). The best cut-off points were -86% in % change in FC levels to predict mucosal healing and -83% for clinical remission., Conclusions: The current study suggests a predictive role of post-induction FC assessment to predict treatment response in IBD patients treated with biologics.

Background: We evaluated an on-demand ferric carboxymaltose (FCM) infusion strategy in inflammatory bowel disease (IBD) patients with iron deficiency anemia (IDA)., Aims: The primary outcome was the response rate to single or multiple FCM infusions after 12 months. Secondary outcomes were the response rate to a single FCM infusion after 3 months and the FCM safety profile., Methods: We retrospectively included 185 IBD patients who received at least one FCM infusion of 500 mg, between 2015 and 2018. FCM was administered to patients with Hb ≤10 g/dL and hypoferritinemia and repeated according to the physician's assessment. Complete response (CR) was defined as Hb ≥12 g/dL (≥13 g/dL for men) or Hb increase ≥2 g/dL. Partial response (PR) was defined as an Hb increase between 1 and 2 g/dL. A univariate analysis was performed at 3 and 12 months., Results: After 12 months, the response rate was 75.1% (CR, 48.6%; PR, 26.4%; mean number of FCM infusions, 1.7 ± 1.1). In total 169/185 patients received a single FCM infusion during the first 3 months and 79.2% achieved response (CR, 56.8%; PR, 22.4%). At univariate analysis, no variable was associated with response. No adverse events were reported., Conclusions: An on-demand strategy was effective and well-tolerated in treating IDA in IBD patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: There is increasing interest in expanding the use of lumen-apposing metal stents (LAMSs) in patients with pancreatic fluid collections (PFCs). The aim of this study was to determine whether there is a hospital volume threshold for which patient outcomes could be optimized., Methods: Data from a large multicenter series of patients with PFCs treated with LAMSs were retrieved. Rate of adverse events (AEs) was the primary outcome. Multivariable models with restricted cubic splines were used to identify a hospital volume threshold by plotting hospital volume against the log odds ratio (OR) of AE rate. Propensity score matching was applied to obtain 2 well-balanced groups according to hospital volume, and univariate/multivariate logistic regression analysis was performed to identify significant predictors of AEs., Results: Overall, 516 patients were included. Increasing hospital volume was associated with a reduced AE rate (P = .03), and the likelihood of experiencing an AE declined as hospital volume increased up to 15 cases. After propensity score matching, 175 patients in the high-volume (>15 cases) and 132 in the low-volume hospital group were compared. Overall, 41 AEs were observed (13.3%), of which 14 (8%) and 27 (20.4%) occurred at high-volume and low-volume centers, respectively (P = .001). Severe and fatal events were observed more frequently in low-volume centers (6% vs 1.7% and 2.2% vs 0%, respectively; P = .05). In multivariate analysis, main pancreatic duct injury (OR, 2.62; 95% confidence interval [CI], 1.26-4.67; P = .02), presence of abnormal vessels (OR, 2.93; 95% CI, 1.41-5.02; P = .006), and institutional experience (OR, 2.95; 95% CI, 1.48-5.90; P = .002) were significant predictors of AEs., Conclusions: With 15 procedures representing the minimum number of cases associated with the lowest risk for postprocedural AEs, hospital volume is associated with improved outcomes. (Clinical trial registration number: NCT03903523.)., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn's disease (CD) following ileocolonic resection is unknown., Aims: To assess the effectiveness of VDZ in this setting., Methods: All consecutive CD patients with a baseline colonoscopy at 6-12 months from the ileocolonic resection showing postoperative recurrence (Rutgeerts score ≥i2) and treated with VDZ after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ and defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up., Results: Fifty-eight patients were included (mean follow-up: 24.8 ± 13.1 months). Endoscopic success was reported in 47.6% of patients. Clinical failure was reported in 19.0% of patients at one year, and in 32.8% of patients at the end of follow-up. A new resection was required in 7 patients (12.1%)., Conclusions: VDZ may be an effective option for the treatment of postoperative recurrence of CD., Competing Interests: Conflict of Interest None declared., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Adalimumab is used to treat ulcerative colitis, but additional effectiveness and safety data are needed., Patients and Methods: This retrospective study considered adults with ulcerative colitis treated with adalimumab at 19 hospitals. Clinical data were collected from the start of treatment, after 2, 6 and 12 months, and at the last visit. Outcome measures of effectiveness were treatment duration, reasons for discontinuation and colectomy., Results: We studied 381 patients treated with adalimumab for a median of 12.1 months. Disease activity at the start of treatment was moderate to severe in 262 cases (68.8%) and endoscopic activity was moderate to severe in 339 cases (89.0%). At week 8, clinical responses were observed in 177 cases (46.5%) and clinical remission in 136 cases (35.7%). At 12 months, remission was observed in 128 cases (33.6%). Overall, 44 patients required colectomy, and 170 patients (44.6%) were still taking adalimumab when data were collected. Variables associated with adalimumab discontinuation were concomitant steroid treatment, severe clinical-endoscopic activity at baseline, need for adalimumab intensification and drug-related adverse events. Variables associated with colectomy were concomitant steroid treatment and high baseline C-reactive protein., Conclusion: Adalimumab is safe and effective for the treatment of ulcerative colitis., Competing Interests: Conflict of Interest None declared., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Several observational studies on Tofacitinib (TOFA) in ulcerative colitis (UC) have been published over the last 2 years., Aims: To estimate effectiveness and safety of TOFA arising from real-world experience., Methods: PubMed Central/Medline and Embase were systematically searched for real-world observational studies on TOFA for the treatment of UC through November 2020., Results: Seven studies comprising 759 patients met the inclusion criteria. The pooled estimate rates were 49% for clinical response, 40% for clinical remission, and 34% for corticosteroid-free clinical remission at induction, while the rates of endoscopic response and endoscopic remission were 37% and 19%, respectively. At maintenance, the pooled estimate rates of clinical response, clinical remission, and corticosteroid-free clinical remission were 36%, 35%, and 24%, respectively. The pooled estimate of incidence rate of adverse events was 53.0 per 100 person-years (PY), while the pooled estimate of incidence rate of withdrawal of TOFA due to adverse events was 9.3 per 100 PY, with a pooled rate of infections of 17.6 per 100 PY., Conclusions: Cumulative analysis of data from real-world studies confirmed the good efficacy of TOFA in UC shown by randomized controlled trials for both induction and maintenance, while the safety profile was consistent with previous reports., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Conventional endoscopic resection techniques such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), represent the standard of care for treatment of superficial gastrointestinal lesions. In 2012 a novel technique called underwater endoscopic mucosal resection (U-EMR) was described by Binmoeller and colleagues. This substantial variation from the standard procedure was afterwards applied at endoscopic submucosal dissection (U-ESD) and recently proposed also for peroral endoscopic myotomy (U-POEM) and endoscopic full-thickness resection (U-EFTR)., Methods: This paper aims to perform a comprehensive review of the current literature related to supporting the underwater resection techniques with the aim to evaluate their safety and efficacy., Results: Based on the current literature U-EMR appears to be feasible and safe. Comparison studies showed that U-EMR is associated with higher "en-bloc" and R0 resection rates for colonic lesions, but lower "en-bloc" and R0 resection rates for duodenal non-ampullary lesions, compared to standard EMR. In contrast to U-EMR, little evidence supporting U-ESD are currently available. A single comparison study on gastric lesions showed that U-ESD had shorter procedural times and allowed a similar "en-bloc" resection rates compared to standard ESD. No comparison studies between U-ESD and ESD are available for colonic lesions. Finally, only some anecdotal experiences have been reported for U-POEM or U-EFTR, and the feasibility and effectiveness of these techniques need to be further investigated., Conclusions: Further prospective studies are necessary to better explore the advantages of underwater techniques compared to the respective standards of care, especially in the setting of U-ESD where consistent data are lacking and where standardization of the technique is needed.

Background: SARS-CoV-2 disease (COVID-19) is a major challenge for the healthcare system and physicians, imposing changes in daily clinical activity., Aims: we aimed to describe what European trainees and young gastroenterologists know about COVID-19 and identify training gaps to implement educational programs., Methods: A prospective web-based electronic survey was developed and distributed via e-mail to all members of the Italian Young Gastroenterologist and Endoscopist Association and to European representatives., Results: One hundred and ninety-seven subjects participated in the survey, of whom 14 (7.1%) were excluded. The majority were gastroenterologists in training (123, 67.7%) working in institutions with COVID-19 inpatients (159, 86.9%), aged ≤30 years (113, 61.8%). The activity of Gastroenterology Units was restricted to emergency visits and endoscopy, with reductions of activities of up to 90%. 84.5% of participants felt that the COVID-19 outbreak impacted on their training, due to unavailability of mentors (52.6%) and interruption of trainee's involvement (66.4%). Most participants referred absence of training on the use of personal protective equipment, oxygen ventilation systems and COVID-19 therapies., Conclusion: COVID-19 outbreak significantly impacted on gastroenterologists' clinical activity. The resources currently deployed are inadequate, and therefore educational interventions to address this gap are warranted in the next future., Competing Interests: Conflicts of Interest None declared., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Previous systematic cumulative analyses of the placebo arm in ulcerative colitis (UC) were limited by the wide heterogeneity in the scores and definitions of response. We aimed at estimating the placebo rates of remission, response, and mucosal healing (MH) in phase 2 and 3 randomized placebo-controlled trials of biologics and small molecule drugs that used homogeneous criteria for the assessment of outcomes., Methods: PubMed Central, Embase, and reference lists of articles were systematically searched through July 2017. Only studies that employed the Mayo score were included., Results: Thirty-one randomized placebo-controlled trials consisting of 2702 patients met the inclusion criteria. At induction, the pooled estimates of the placebo rates of remission, response, and MH were 9% (95% confidence interval [CI], 7%-12%; range: 0%-29%; I2 = 75.0%), 34% (95% CI, 31%-38%; range: 12%-75%; I2 = 61.3%), and 26% (95% CI, 22%-30%; range: 2%-65%; I2 = 77.7%), respectively. At maintenance, the pooled estimates of the placebo rates of remission, response, and MH were 14% (95% CI, 10%-18%; range: 6%-30%; I2 = 73.0%), 23% (95% CI, 20%-27%; range: 18%-36%; I2 = 53.0%), and 19% (95% CI, 15%-23%; range: 12%-30%; I2 = 65.0%), respectively. Among the variables assessed by logistic regression analysis, multiple factors influenced the outcomes of placebo arms, including concomitant systemic steroids at baseline, endoscopic central reading, being naïve or non-naïve to anti-TNFs, and disease duration., Conclusions: Despite the wide use of homogeneous criteria for the assessment of clinical and endoscopic outcomes, a high heterogeneity among placebo arms of modern trials in UC still exists., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Direct-acting antivirals (DAAs) revolutionised the treatment of chronic HCV-related disease achieving high rates of sustained virological response (SVR), also in more advanced patients, with a good safety profile and a proven positive effect on the reduction of risk of HCC occurrence. Nevertheless, patients with an history of successfully treated early HCC were initially excluded from pivotal trials. Although some initial retrospective studies, affected by several methodological issues, raised concerns regarding a possible harmful effect on the risk of HCC recurrence after antiviral therapy, more recent prospective studies and meta-analyses provided evidence that risk of HCC recurrence after DAA therapy is similar, or even lower, than that observed in patients treated with interferon or in DAA-untreated controls. In the future, a meta-analyses of individual patient data would be necessary to definitively close this clinical debate, as well as prospective studies assessing ‘true endpoints’, such as overall survival.

Binge drinking (BD) is a common pattern of alcohol consumption among adolescents. At present few data are available on the possible relationship between BD and alcohol use disorders (AUD) in adolescents. The aim of this study was to assess the prevalence of BD and relationship between BD behavior and AUD among adolescents. A total of 2704 students attending 10 purposively selected high schools from three Italian provinces were surveyed. Questionnaires regarding socio-demographic data, pattern and amount of alcohol intake, smoking habits, use of illicit drugs, and physical activity were administered. AUD and affective disorders were also evaluated. Alcohol intake was reported by 2126 participants; 1278 reported at least one episode BD in the last year and 715 in the last month. A diagnosis of AUD was made in 165 adolescents. The prevalence of AUD was higher in adolescents that reported BD behavior than in those that did not report BD (11.6% vs 0.9%, respectively; p < 0.0001). Logistic regression showed a positive relationship between a diagnosis of AUD and BD behavior (OR 9.6; 95% CI 4.7-22·9; p < 0.0001). In conclusion alcohol consumption with the pattern of BD among adolescents is highly related to development of AUD.

Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections in the world and is a leading cause of morbidity and mortality in hospitalized patients.Although several antibiotics effectively treat CDI, some individuals do not respond to these drugs and may be cured by transplanting stool from healthy donors. This procedure, termed Faecal Microbiota Transplantation (FMT), has demonstrated remarkable efficacy as a treatment for recurrent CDI.FMT has also been investigated in other diseases and disorders where perturbations to the gut microbiota have been theorized to play a causative role in pathogenesis and severity, such as inflammatory bowel disease (IBD). Although FMT is currently not recommended to cure IBD patients in clinical practice, several studies have recently been carried out with promising results. The aim of future research is therefore to standardize protocols and develop FMT as a therapeutic option for these patients.This review summarizes data on the use of FMT as a treatment for CDI and IBD, with special attention given to studies conducted in European countries.

Prognostic ability of BCLC-B Subclassification in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Background and aims. A subclassification system for intermediate hepatocellular carcinoma (HCC) was recently proposed to optimize treatment allocation. The aim of this study was to assess the prognostic ability of that substaging proposal., Patients and Methods: This is a retrospective multicenter cohort study including patients with intermediate HCC treated with transarterial chemoembolization (TACE). Predictors of survival were identified using the Cox proportional regression model., Results: 289 Barcelona Clinic Liver Cancer (BCLC) B patients were included. Median overall survival of the whole cohort was 23 months (C.I. 95% 20.2- 25.8). Child A status (H.R. 1.35, C.I. 95% 1.02-1.78) and tumour burden beyond the up-to-seven criterion (H.R. 1.39, C.I. 95% 1.07- 1.80) were independent prognostic factors for overall survival on multivariate analysis. Analysis of the substages showed that median survival was 33.0 months for B1 stage (n = 81), 20.8 months for B2 stage (n = 106), 16.1 months for B3 stage (n = 24), 22.2 months for B4 stage (n = 42) and 15.0 months for quasi-C stage (n = 36). Regarding the discriminatory ability of the substaging proposal, the log rank test showed a significant survival difference for B1vs. B4 (p = 0.003) and B1 vs. Quasi-C (p = 0.039) and a trend for B1 vs. B2 (p = 0.05) and B1 vs. B3 (p = 0.05)., Conclusions: Apart from substage B1, BCLC-B subclassification does not discriminate perfectly patients treated with TACE. Also some patients in substage B4 can benefit from TACE.

Background: Few studies investigated the role of mycophenolate mofetil in inflammatory bowel disease, and none of them had specifically focused on patients with previous multiple intolerances and/or nonresponses to conventional immunosuppressants and biologics., Aims: To evaluate clinical benefit and tolerability profile of mycophenolate mofetil in patients with inflammatory bowel disease and limited treatment options., Methods: All consecutive patients with previous multiple intolerances and/or nonresponses to immunosuppressants and biologics who started an off-label treatment with mycophenolate mofetil from January 2014 to February 2016 were entered in a prospectively maintained database., Results: Twenty-four patients were included. Four weeks after initiation of mycophenolate mofetil therapy, a steroid-free remission was achieved in 4 patients (16.7%), while a clinical response in 13 (54.1%). At the end of follow-up, 12 patients (50.0%) remained on mycophenolate mofetil. Six achieved and maintained steroid-free remission throughout the study period (25.0%), and a further 6 patients (25.0%) achieved a clinical response with complete discontinuation of steroids. Twelve patients (50.0%) were considered as treatment failure, and five of them underwent surgery., Conclusions: This is the first experience reporting a clinical benefit and tolerability of mycophenolate mofetil in patients with inflammatory bowel disease and multiple previous failures to other immunosuppressants and/or biologics., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease.

Background: Drugs and herbal products can induce autoimmune hepatitis. We assessed frequency and clinical outcomes of patients suffering from drug-induced autoimmune hepatitis., Methods: All patients with drug-induced liver injury admitted between 2000 and 2011 were retrospectively studied. Diagnoses of drug-induced autoimmune hepatitis and idiopathic autoimmune hepatitis were made according to simplified criteria. After discharge, all patients had regular follow-up and were contacted to update outcomes., Results: Among 10,270 in-hospital patients, 136 (1.3%) were diagnosed with drug-induced liver injury. Among them, 12 (8.8%) were diagnosed as drug-induced autoimmune hepatitis (41.7% males, age range 17-73); 8 (66.7%) were with jaundice at admission. Liver biopsies showed a pattern compatible with drug-induced autoimmune hepatitis, featured by severe portal inflammation and lymphoplasmacytic infiltrate. Drug-induced autoimmune hepatitis group had a shorter duration of drug intake, and higher values of transaminases and gamma globulins. All patients received immunosuppressive therapy with subsequent clinical remission, and five achieved a steroid-free long-term remission., Conclusions: A diagnosis of drug-induced autoimmune hepatitis was quite rare in our cohort, and clinical pattern was similar to idiopathic autoimmune hepatitis. Severe portal inflammation, prominent portal-plasma cells, rosette formation and severe focal necrosis were significantly more frequent in drug-induced autoimmune hepatitis as compared to drug-induced liver injury., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: In Chronic Hepatitis C (CHC), the influence of steatosis on liver stiffness measurement (LSM) is still debated. We assessed the impact of steatosis and its ultrasonographical sign - bright liver echo pattern (BLEP) - on LSM values and on transient elastography (TE) accuracy for the diagnosis of liver fibrosis, in a cohort of consecutive patients with Genotype 1 (G1) CHC., Methods: Patients (n=618) were assessed by clinical, ultrasonographic and histological (Scheuer score) features. TE was performed using the M probe., Results: Male gender (p=0.04), steatosis as continuous variable (p<0.001), severity of necroinflammation (p=0.02) and stage of fibrosis (p<0.001) were associated with LSM by multivariate linear regression analysis. Among patients within the same fibrosis stages (F0-F2 and F3-F4; F0-F3 and F4), mean LSM values, expressed in kPa, were significantly higher in subjects with moderate-severe steatosis (⩾20% at liver biopsy) compared with those without, as well as in patients with BLEP on US compared with their counterpart. In subjects without severe fibrosis (F0-F2) and without cirrhosis (F0-F3), a higher rate of false-positive LSM results was observed in patients with steatosis ⩾20% compared with those without (F0-F2: 35.3% vs. 17.9%; F0-F3: 38.9% vs. 16.6%), and in patients with BLEP on US (F0-F2: 28.0% vs. 18.3%; F0-F3: 29.7% vs. 17.8%) compared with their counterpart., Conclusions: In patients with G1 CHC, the presence of moderate-severe steatosis, detected by histology or by US, should always be taken into account in order to avoid overestimations of liver fibrosis assessed by TE., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Aim: To investigate clinical and biochemical features of hepatorenal syndrome (HRS), to assess short and long-term survival evaluating potential predictors of early mortality., Methods: Sixty-two patients with liver cirrhosis and renal failure, defined as a serum creatinine value > 1.5 mg/dL on at least two measurements within 48 h, admitted to our tertiary referral Unit from 2001 to 201, were retrospectively reviewed. Among them, 33 patients (53.2%) fulfilled the revised criteria of the International Ascites Club for the diagnosis of HRS. Twenty-eight patients were treated with combinations of terlipressin and albumin, two with dopamine and albumin, and three with albumin alone. No patients were suitable for liver transplantation. Complete response was defined as normalization of creatinine levels to less than 1.5 mg/dL, partial response as a decrease of at least 50% but not to less than 1.5 mg/dL, no response as no reduction in creatinine or a decrease of less 50% compared to pre-treatment values. All of the patients were followed up for at least 1 year until January 2013., Results: HRS type 1 was diagnosed in 15 patients (45.5%). Hepatitis C virus infection was the primary etiology (69.6%), followed by alcohol (15.2%), and cryptogenesis (15.2%). Complete response to therapy was obtained in only 3 cases (9.1%) and partial response in 7 patients (21.2%). Median survival was 30 d (range: 10-274) without significant differences between type 1 and type 2 HRS. By univariate analysis, Child-Pugh class C (P = 0.009), presence of hepatocellular carcinoma (P = 0.04), low serum sodium (P = 0.02), high bilirubin values (P = 0.009) and high Model for End-stage Liver Disease (MELD) score (P = 0.03) were predictive factors of 30-d mortality. By multivariate analysis, only serum sodium < 132 mEq/L (OR = 31.39; P = 0.02) and MELD score > 27 (OR = 18.72; P = 0.01) were independently associated with a survival of less than one month., Conclusion: HRS still has a poor prognosis, even when vasoactive drug therapies are extensively used.

Surgical resection and imaging guided treatments play a crucial role in the management of hepatocellular carcinoma (HCC). Although the primary end point of treatment of HCC is survival, radiological response could be a surrogate end point of survival, and has a key role in HCC decision-making process. However, radiological assessment of HCC treatment efficacy is often controversial. There are few doubts on the evaluation of surgical resection; in fact, all known tumor sites should be removed. However, an unenhancing partial linear peripheral halo, in most cases, surrounding a fluid collection reducing in size during follow-up is demonstrated in successfully resected tumor with bipolar radiofrequency electrosurgical device. Efficacy assessment of locoregional therapies is more controversial and differs between percutaneous ablation (e.g., radiofrequency ablation and percutaneous ethanol injection) and transarterial treatments (e.g., conventional transarterial chemoembolization, transarterial chemoembolization with drug eluting beads and radioembolization). Finally, a different approach should be used for new systemic agent that, though not reducing tumor mass, could have a benefit on survival by delaying tumor progression and death. The purpose of this brief article is to review HCC imaging appearance after treatment.

Primary biliary cirrhosis is a slowly progressive cholestatic autoimmune liver disease that mainly affects middle-aged women with an estimated prevalence ranging from 6.7 to 402 cases per million. Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber disease, is an autosomal dominant disorder characterized by angiodysplastic lesions (telangiectases and arteriovenous malformations) that can affect many organs, including liver, with a prevalence of 1-2 cases per 10000. We describe the coexistence, for the first time to our knowledge, of these two rare diseases in a 50-year old Caucasian woman. In this setting, the relevance of an accurate medical history, the role of liver histology and the characterization of liver involvement through dynamic imaging techniques can be emphasized.

Aim: To investigate the clinical course of untreatable hepatocellular carcinoma (HCC) identified at any stage and to identify factors associated with mortality., Methods: From January 1999 to December 2010, 320 out of 825 consecutive patients with a diagnosis of HCC and not appropriate for curative or palliative treatments were followed and managed with supportive therapy. Cirrhosis was diagnosed by histological or clinical features and liver function was evaluated according to Child-Pugh score. The diagnosis of HCC was performed by Ultra-Sound guided biopsy or by multiphasic contrast-enhanced computed tomography or gadolinium-enhanced magnetic resonance imaging. Data were collected for each patient including all clinical, laboratory and imaging variables necessary for the outcome prediction staging systems considered. HCC staging was performed according Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program scores. Follow-up time was defined as the number of months from the diagnosis of HCC to death. Prognostic baseline variables were analyzed by multivariate Cox analysis to identify the independent predictors of survival., Results: Seventy-five per cent of patients had hepatitis C. Ascites was present in 169 patients (53%), while hepatic encephalopathy was present in 49 patients (15%). The Child-Pugh score was class A in 105 patients (33%), class B in 142 patients (44%), and class C in 73 patients (23%). One hundred patients (31%) had macroscopic vascular invasion and/or extra-hepatic spread of the tumor. A single lesion > 10 cm was observed in 34 patients (11%), while multinodular HCC was present in 189 patients (59%). Thirty nine patients (12%) were BCLC early (A) stage, 55 (17%) were BCLC intermediate (B) stage, 124 (39%) were BCLC advanced (C) stage, and 102 (32%) were end-stage BCLC (D). At the time of this analysis (July 2011), 28 (9%) patients were still alive. Six (2%) patients who were lost during follow-up were censored at the last visit. The overall median survival was 6.8 mo, and the 1-year survival was 32%. The 1-year survival according to BCLC classes was 100%, 79%, 12% and 0%, for BCLC A, B, C and D, respectively. There was a significant difference in survival between each BCLC class. The median survival of patients of BCLC stages A, B, C and D was 33, 17.4, 6.9, and 1.8 mo, respectively (P < 0.05 for comparison between stages). The median survival of Child-Pugh A, B and C classes were 9.8 mo (range 6.4-13), 6.1 (range 4.9-7.3), and 3.7 (range 1.5-6), respectively (P < 0.05 for comparison between stages). By univariate analysis, the variables significantly associated to an increased liklihood of mortality were Eastern Cooperative Oncology Group performance status (PS), presence of ascites, low level of albumin, elevated level of bilirubin, international normalized ratio (INR) and Log-[(α fetoprotein (AFP)]. At multivariate analysis, mortality was independently predicted by bad PS (P < 0.0001), high INR values (P = 0.0001) and elevated Log-(AFP) levels (P = 0.009)., Conclusion: This study confirms the heterogeneous behavior of untreated HCC. BCLC staging remains an important prognostic guide and may be important in decision-making for palliative treatment.