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Background: There are conflicting studies reporting both an increase and a decrease in vitamin B12 (VB12) levels in non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to dissect the effects of steatosis and fibrosis on VB12., Methods: This is a cross-sectional study including all patients with a vibration-controlled transient elastography (VCTE) performed at the Hospital Miguel Servet (Zaragoza, Spain) between 2019 and 2022 for a chronic liver disease and having a recent blood test for VB12 levels. Liver fibrosis was assessed by VCTE and hepatic steatosis by ultrasonography and/or through controlled attenuation parameter (CAP)., Results: 1195 patients (NAFLD n = 441, other chronic liver disease n = 754) were included. Median age was 57 years, 53% female. Patients with NAFLD had lower levels of VB12 compared to the rest of chronic liver diseases (289 vs. 313 pg/mL, p < 0.001). A significant negative correlation was observed between VB12 levels and hepatic steatosis measured by CAP ( r = -0.13, p < 0.001). A significant positive correlation was observed between VB12 levels and liver stiffness in patients with NAFLD in both sexes (men r = 0.31, p < 0.001 and women r = 0.15, p = 0.016). A significant association between VB12 levels and liver fibrosis in cirrhosis stage was observed in patients with NAFLD (OR 1.06, 95% CI, 1.025-1.098, p = 0.001)., Conclusion: VB12 levels were lower with greater hepatic steatosis. In NAFLD, VB12 levels were lower compared to other chronic liver diseases but their levels increased with higher liver stiffness and in cirrhosis stage.

Introduction: percutaneous endoscopic gastrostomy (PEG) is considered as a safe and effective method for nutritional support in patients with malnutrition and swallowing impairment with an estimated survival of over two months. Some indications, such as advanced cognitive decline, contraindicate the technique., Materials and Methods: all patients who underwent PEG placement between January 2001 and May 2019 were included. Clinical data, indication, complications, and mortality were retrospectively analyzed., Results: a total of 648 patients (46.5 % male, mean age 70 ± 18.5 years) were included. The most common indications for PEG were advanced cognitive decline (31.5 %) and cerebrovascular disease (18.8 %). The mean follow-up was 12.07 months (IQR 3.27-34.73); 39.5 % of patients experienced complications (systemic 17.9 %, local 28.5 %). The most frequent were bronchoaspiration (9.7 %) and rupture/dysfunction (13.9 %), respectively. The presence of early complications (HR 1.63 [1.20-2.21]) and age (HR 1.02 [1.01-1.02]) was associated with shorter survival time, while female sex was a protective factor (HR 0.78 [0.66-0.94])., Conclusions: PEG is not without complications, with 39.5 % of patients experiencing them. Patients with early complications, male sex and older age have lower survival following PEG placement.

Background: The response to SARS-CoV-2 vaccination decreases in inflammatory bowel disease (IBD) patients, specially under anti-TNF treatment. However, data on medium-term effectiveness are limited, specially using new recommended seroconversion rate (>260BAU/mL). Our aim was to evaluate the 6-month>260 BAU-seroconversion rate after full vaccination and after booster-dose., Methods: VACOVEII is a Spanish multicenter, prospective study promoted by GETECCU. IBD patients full vaccinated against SARS-CoV-2 and without previous COVID-19 infection, treated or not with immunosuppressants, were included. The booster dose was administered 6 months after the full vaccination. Seroconversion was set at 260BAU/mL, according to most recent recommendations and was assessed 6 months after the full vaccination and 6 months after booster-dose., Results: Between October 2021 and March 2022, 313 patients were included (124 no treatment or mesalazine; 55 immunomodulators; 87 anti-TNF; 19 anti-integrin; and 28 ustekinumab). Most patients received mRNA-vaccines (86%). Six months after full vaccination, overall seroconversion rate was 44.1%, being significantly lower among patients on anti-TNF (19.5%, p<0.001) and ustekinumab (35.7%, p=0.031). The seroconversion rate after booster was 92%. Again, anti-TNF patients had a significantly lower seroconversion rate (67%, p<0.001). mRNA-vaccine improved seroconversion rate (OR 11.720 [95% CI 2.26-60.512])., Conclusion: The full vaccination regimen achieves suboptimal response in IBD patients, specially among those anti-TNF or ustekinumab. The booster dose improves seroconversion rate in all patients, although it remains limited in those treated with anti-TNF. These results reinforce the need to prioritize future booster doses in patients on immunosuppressants therapy, specially under anti-TNF, and using mRNA-vaccines., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Metabolic-associated steatohepatitis liver disease (MASLD) currently impacts a quarter of the global population, and its incidence is expected to increase in the future. As a result, hepatocellular carcinoma associated with MASLD is also on the rise. Notably, this carcinoma does not always develop alongside liver cirrhosis, often leading to a more advanced stage at diagnosis. The challenge lies in accurately identifying patients who are at a higher risk to tailor screening processes effectively. Additionally, several therapeutic approaches are being explored to prevent hepatocellular carcinoma, although there are no universally accepted guidelines yet.

Objective: The recommendations of the Spanish Ministry of Health on vaccination in risk groups include mesalazine among the treatments with a possible negative effect on its effectiveness. However, this is not the recommendation of most experts. Our objective was to evaluate the effect of mesalazine on the humoral response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD)., Methods: VACOVEII is a Spanish, prospective, multicenter study promoted by GETECCU, which evaluates the effectiveness of the SARS-CoV-2 vaccine in patients with IBD. This study includes IBD patients who have recieved the full vaccination schedule and without previous COVID-19 infection. Seroconversion was set at 260BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectiveness of the vaccine between patients treated with mesalazine and patients without treatment., Results: A total of 124 patients without immunosuppressive therapy were included, of which 32 did not receive any treatment and 92 received only mesalazine. Six months after full vaccination, no significant differences are observed in the mean concentrations of IgG anti-S between both groups. In the multivariate analysis, antibody titers were independently associated with the use of mRNA vaccines and with SARS-CoV-2 infection., Conclusion: Mesalazine does not have a negative effect on the response to SARS-CoV-2 vaccines in IBD patients., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Background: We lack predictors of response to biologics in the management of patients with inflammatory bowel disease (IBD). A recent study has shown a significant association between HLA-DQA1*05 carriers and the development of loss of response to anti-tumor necrosis factor (TNF) mediated by immunogenicity., Methods: Retrospective single-center cohort study including IBD patients who had received anti-TNF therapy as a first biologic and whose HLA-DQA1*05 had been determined. Primary nonresponse and secondary failure (assessed by survival analysis) have been evaluated as well as safety outcomes., Results: A total of 199 IBD patients (161 [81%] with Crohn's disease and 38 [19%] with ulcerative colitis) were included. A total of 42.4% were HLA-DQA1*05 carriers and 60% received combination therapy at the start of anti-TNF treatment. Median follow-up was 24 (interquartile range, 11-66) months. No statistically significant differences were found in primary nonresponse to anti-TNF (89.3% vs 87.8%; P = .825), depending on HLA carriers and noncarriers. No differences in secondary loss of response according to HLA variant in any of the analyses performed (full cohort, according to IBD or anti-TNF type) were observed. Again, no differences were observed in patients treated with combination therapy. In terms of safety, no significant differences were found in the rate of infusion reactions or serious adverse events., Conclusion: In our real-life cohort of IBD patients treated for the first time with anti-TNF, being an HLA-DQA1*05 carrier did not act as a predictor of response failure, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the variant., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: the risk of hepatocellular carcinoma (HCC) after eradication of the hepatitis C virus (HCV) is highly variable in patients with advanced fibrosis (F3). Long-term surveillance for HCC after sustained virological response (SVR) is controversial in these patients. The objective of this study was to describe the post-SVR follow-up in clinical practice in patients with F3 and determine the predictive factors for the development of HCC., Patients and Methods: a multicenter, observational and retrospective study was performed, which included HCV-monoinfected patients with F3 fibrosis determined by transient elastography who achieved SVR between 2015 and 2022, with follow-up until May 2023. Clinical-demographic, laboratory, elastography, and ultrasound variables were recorded before and after treatment. A descriptive and inferential analysis, Cox regression analysis and survival analysis were carried out with the R statistical software., Results: two hundred and nineteen patients were included in the study (65.3 % males, median age 57 years), and 175 (79.9 %) received ultrasound screening after SVR for 62 (6-90) months. The prescribing service was the only independent variable related to performing ultrasound surveillance (p = 0.004). Eight patients developed HCC. In multivariate analysis adjusted for sex, age, presence of diabetes and alcohol consumption, a post-SVR FIB-4 ≥ 3.25 was associated with a 12-fold increase in HCC risk. The cumulative probability of HCC was higher in the group of patients with FIB-4 ≥ 3.25 after SVR (p < 0.001)., Conclusion: post-SVR follow-up of patients with F3 fibrosis is variable in clinical practice. Using the FIB-4 after SVR allows us to identify those patients with a higher risk of HCC who benefit from biannual ultrasound screening.

Introduction: Intra-abdominal abscesses complicating Crohn's disease [CD] are a challenging situation. Their management, during hospitalisation and after resolution, is still unclear., Methods: Adult patients with CD complicated with intra-abdominal abscess. who required hospitalisation, were included from the prospectively maintained ENEIDA registry from GETECCU. Initial strategy effectiveness and safety to resolve abscess was assessed. Survival analysis was performed to evaluate recurrence risk. Predictive factors associated with resolution were evaluated by multivariate regression and predictive factors associated with recurrence were assessed by Cox regression., Results: In all, 520 patients from 37 Spanish hospitals were included; 322 [63%] were initially treated with antibiotics alone, 128 [26%] with percutaneous drainage, and 54 [17%] with surgical drainage. The size of the abscess was critical to the effectiveness of each treatment. In abscesses < 30 mm, the antibiotic was as effective as percutaneous or surgical drainage. However, in larger abscesses, percutaneous or surgical drainage was superior. In abscesses > 50 mm, surgery was superior to percutaneous drainage, although it was associated with a higher complication rate. After abscess resolution, luminal resection was associated with a lower 1-year abscess recurrence risk [HR 0.43, 95% CI 0.24-0.76]. However, those patients who initiated anti-TNF therapy had a similar recurrence risk whether luminal resection had been performed., Conclusions: Small abscesses [<30mm] can be managed with antibiotics alone; larger ones require drainage. Percutaneous drainage will be effective and safer than surgery in many cases. After discharge, anti-TNF therapy reduces abscess recurrence risk in a similar way to bowel resection., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The eradication of the hepatitis C virus (HCV) has revolutionized the hepatology paradigm, halting the progression of advanced liver disease in patients with chronic infection and reducing the risk of hepatocarcinoma. In addition, treatment with direct-acting antivirals can reverse the lipid and carbohydrate abnormalities described in HCV patients. Although HCV eradication may reduce the overall risk of vascular events, it is uncertain whether altered lipid profiles increase the risk of cerebrovascular disease in certain patients. We have conducted a review on HCV and lipid and carbohydrate metabolism, as well as new scientific advances, following the advent of direct-acting antivirals.

Background: Numerous scores are designed to predict outcomes of patients with liver cirrhosis. Our study aimed to evaluate the ability of the Liver Disease Undernutrition Screening Tool (LDUST) in predicting mortality and decompensation in outpatients with clinically significant portal hypertension (CSPH). We hypothesized that LDUST could help identify patients in need of nutritional supplementation and intervention., Methods: A prospective study of 57 CSPH patients (36.8% female, mean age: 63.5 ± 9.9 years) with a median follow-up of 41 months was conducted. Baseline liver function, nutrition, and sarcopenia were assessed, alongside LDUST. During follow-up, the occurrence of liver decompensation, hospital admission, need for emergency care, and mortality were evaluated., Results: A total of 56.1% of patients were Child A, and the most frequent etiology was alcohol (50.9%). Malnutrition risk according to LDUST raised mortality (HR: 25.96 (1.47-456.78)), decompensation (HR 9.78 (2.08-45.89)), and admission (HR 4.86 (1.09-21.61)) risks in multivariate Cox analysis. Combining LDUST with Child and MELD scores improved their decompensation prediction (0.936 vs. 0.811 and 0.866 vs. 0.700)., Conclusions: The LDUST has a solid ability to predict complications in cirrhosis outpatients with CSPH, and its integration with Child and MELD models enhances their predictive power. LDUST implementation could identify individuals necessitating early nutritional support.

Liver diseases are the major predisposing conditions for the development of malnutrition, sarcopenia, and frailty. Recently, the mechanism of the onset of these complications has been better established. Regardless of the etiology of the underlying liver disease, the clinical manifestations are common. The main consequences are impaired dietary intake, altered macro- and micronutrient metabolism, energy metabolism disturbances, an increase in energy expenditure, nutrient malabsorption, sarcopenia, frailty, and osteopathy. These complications have direct effects on clinical outcomes, survival, and quality of life. The nutritional status should be assessed systematically and periodically during follow-up in these patients. Maintaining and preserving an adequate nutritional status is crucial and should be a mainstay of treatment. Although general nutritional interventions have been established, special considerations are needed in specific settings such as decompensated cirrhosis, alcohol-related liver disease, and metabolic-dysfunction-associated fatty liver disease. In this review, we summarize the physiopathology and factors that impact the nutritional status of liver disease. We review how to assess malnutrition and sarcopenia and how to prevent and manage these complications in this setting.

Background & Aims: Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardiovascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradication of HCV, with positive effects on metabolic health although paradoxically associated with increased total and LDL-cholesterol. The aims of this study were 1) to characterize dyslipidemia (lipoprotein content, number, and size) in naive HCV-infected individuals and 2) to evaluate the longitudinal association of metabolic changes and lipoparticle characteristics after DAA therapy., Methods: We conducted a prospective study with one-year follow-up. 83 naive outpatients treated with DAAs were included. Those co-infected with HBV or HIV were excluded. IR was analyzed using the HOMA index. Lipoproteins were studied by fast-protein liquid chromatography (FPLC) and Nuclear Magnetic Resonance Spectroscopy (NMR)., Results: FPLC analysis showed that lipoprotein-borne HCV was only present in the VLDL region most enriched in APOE. There was a lack of association between HOMA and total cholesterol or cholesterol carried by LDL or HDL at baseline. Alternatively, a positive association was found between HOMA and total circulating triglycerides (TG), as well as with TG transported in VLDL, LDL, and HDL. HCV eradication with DAAs resulted in a strong and significant decrease in HOMA (-22%) and HDL-TG (-18%) after one-year follow-up., Conclusions: HCV-dependent lipid abnormalities are associated with IR and DAA therapy can reverse this association. These findings may have potential clinical implications as the HDL-TG trajectory may inform the evolution of glucose tolerance and IR after HCV eradication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Retrospective studies suggest that coronavirus disease (COVID-19) commonly involves gastrointestinal (GI) symptoms and complications. Our aim was to prospectively evaluate GI manifestations in patients hospitalized for COVID-19., Methods: This international multicentre prospective cohort study recruited COVID-19 patients hospitalized at 31 centres in Spain, Mexico, Chile, and Poland, between May and September 2020. Patients were followed-up until 15 days post-discharge and completed comprehensive questionnaires assessing GI symptoms and complications. A descriptive analysis as well as a bivariate and multivariate analysis were performer using binary logistic regression. p<0.05 was considered significant., Results: Eight hundred twenty-nine patients were enrolled; 129 (15.6%) had severe COVID-19, 113 (13.7%) required ICU admission, and 43 (5.2%) died. Upon admission, the most prevalent GI symptoms were anorexia (n=413; 49.8%), diarrhoea (n=327; 39.4%), nausea/vomiting (n=227; 27.4%), and abdominal pain (n=172; 20.7%), which were mild/moderate throughout the disease and resolved during follow-up. One-third of patients exhibited liver injury. Non-severe COVID-19 was associated with ≥2 GI symptoms upon admission (OR 0.679; 95% CI 0.464-0.995; p=0.046) or diarrhoea during hospitalization (OR 0.531; 95% CI 0.328-0.860; p=0.009). Multivariate analysis revealed that worse hospital outcomes were not independently associated with liver injury or GI symptoms., Conclusion: GI symptoms were more common than previously documented, and were mild, rapidly resolved, and not independently associated with COVID-19 severity. Liver injury was a frequent complication in hospitalized patients not independently associated with COVID-19 severity., (Copyright © 2022 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Aims: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD., Methods: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54., Results: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]., Conclusions: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce., Methods: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered., Results: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection., Conclusions: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies., Competing Interests: Declaration of Competing Interest MM has served as a speaker, consultant and advisory member for or has received research funding from AbbVie, Gilead, Janssen, MSD, Pfizer, Shire Pharmaceuticals, Faes, Takeda, Tillots; PN has served as a speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Janssen, Takeda, Roche, Sandoz, Ferring, Adacyte, Faes Farma, Kern Pharma, Pfizer, Shire Pharmaceuticals, Vifor Pharma, Chiesi and Tillots; MDM-A has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Shire Pharmaceuticals, Tillotts Pharma, FaesPharma; MB-W has served as a speaker, consultant and advisory member for or has received research funding from MSD, Ferring, Abbvie, Janssen, Biogen and Takeda; MC has served as a speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Takeda, Jannsen, Pfizer, Otsuka Pharmaceutical, Chiesi, Ferring, Shire Pharmaceuticals and Dr. Falk Pharma; MS-A has served as a speaker, consultant and advisory member for or has received research funding from Takeda, Janssen, MSD, Abbvie, Ferring, Chiesi, Tillots and Pfizer; MBA has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gillead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma; YZ has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Takeda, Kern Pharma, Biogen; JPG has served as a speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene, Gilead, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, and Vifor Pharma; JG has served as a speaker, consultant and advisory member for or has received research funding from Roche, MSD, Abbvie, Kern Pharma, Takeda, Janssen, Pfizer, Ferring, Chiesi and GE Healthcare; DB has served as a speaker, consultant and advisory member for or has received research funding from Abbvie, Janssen, Ferring, Pfizer, and Takeda; DC-D has served as a speaker, consultant and advisory member for or has received research funding from MSD, Ferring, Abbvie, Janssen, Faes Farma, Pfizer, Tillots and Takeda; SM has served as a speaker, consultant and advisory member for or has received research funding from MSD, Ferring, Abbvie, Janssen, Pfizer and Takeda; LM has served as a speaker and advisory member for or has received research funding from MSD, Takeda, Janssen, Abbvie and Pfizer; FC has served as a speaker, consultant and advisory member for or has received research funding from Takeda, Janssen, MSD, and Ferring; MC has served as a speaker, consultant and advisory member for or has received research funding from Takeda, Janssen, Faes Farma, and MSD; ED has served as a speaker, consultant and advisory member for or has received research funding from AbbVie, Adacyte Therapeutics, Celltrion, Gilead, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, Tillots, Ferring, and Thermofisher; the remaining authors have no potential conflicts to declare., (Copyright © 2022. Published by Elsevier Ltd.)

Branched-chain amino acids (BCAA) supplementation is used to promote protein synthesis in different clinical conditions in which proteolysis is increased. In addition, lower plasma BCAA levels have been related to an increased risk of hepatic encephalopathy in liver cirrhosis. In this article we will review the role of supplementation with BCAAs and BCAA derivative β-hydroxy-β-methylbutyrate (HMB) in liver cirrhosis, focusing on nutritional and clinical effects. Evidence shows that BCAA supplementation slightly increases muscle mass and body mass index, with an upward trend in muscular strength and no change in fat mass. Moreover, BCAA supplementation improves symptoms of hepatic encephalopathy, and is indicated as second-line therapy. The evidence is more limited for BCAA derivatives. HMB supplementation appears to increase muscle mass in chronic diseases associated with cachexia, although this effect has not yet been clearly demonstrated in liver cirrhosis studies. To date, HMB supplementation has no clinical indication in liver cirrhosis.

Background: Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited., Methods: At 18 centers, we randomly assigned patients who presented with acute pancreatitis to receive goal-directed aggressive or moderate resuscitation with lactated Ringer's solution. Aggressive fluid resuscitation consisted of a bolus of 20 ml per kilogram of body weight, followed by 3 ml per kilogram per hour. Moderate fluid resuscitation consisted of a bolus of 10 ml per kilogram in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 ml per kilogram per hour in all patients in this group. Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to the patient's clinical status. The primary outcome was the development of moderately severe or severe pancreatitis during the hospitalization. The main safety outcome was fluid overload. The planned sample size was 744, with a first planned interim analysis after the enrollment of 248 patients., Results: A total of 249 patients were included in the interim analysis. The trial was halted owing to between-group differences in the safety outcomes without a significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; adjusted relative risk, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P = 0.32). Fluid overload developed in 20.5% of the patients who received aggressive resuscitation and in 6.3% of those who received moderate resuscitation (adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94, P = 0.004). The median duration of hospitalization was 6 days (interquartile range, 4 to 8) in the aggressive-resuscitation group and 5 days (interquartile range, 3 to 7) in the moderate-resuscitation group., Conclusions: In this randomized trial involving patients with acute pancreatitis, early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes. (Funded by Instituto de Salud Carlos III and others; WATERFALL ClinicalTrials.gov number, NCT04381169.)., (Copyright © 2022 Massachusetts Medical Society.)

Background and Aims: Malnutrition is a condition that has a great impact on oncology patients. Poor nutritional status is often associated with increased morbidity and mortality, increased toxicity, and reduced tolerance to chemotherapy, among other complications. The recently developed GLIM criteria for malnutrition aim to homogenize its diagnosis, considering the baseline disease status. We aimed to evaluate the performance of these new criteria for the prediction of complications and mortality in patients with cancer. Methods: This work is a prospective, single-center study. All outpatients under active treatment for head and neck, upper gastrointestinal, and colorectal tumors between February and October 2020 were recruited. These patients were followed up for 6 months, assessing the occurrence of complications and survival based on GLIM diagnoses of malnutrition. Results: We enrolled 165 outpatients, 46.66% of whom were malnourished. During the 6-month follow-ups, patients with malnutrition (46.7%, according to GLIM criteria) had a ~3-fold increased risk of hospital admission (p < 0.001) and occurrence of severe infection (considered as those requiring hospitalization, intravenous antibiotics, and/or drainage by interventional procedures) (p = 0.002). Similarly, malnourished patients had a 3.5-fold increased risk of poor pain control and a 4.4-fold increased need for higher doses of opioids (both p < 0.001). They also had a 2.6-fold increased risk of toxicity (p = 0.044) and a 2.5-fold increased likelihood of needing a dose decrease or discontinuation of cancer treatment (p = 0.011). The 6-month survival of malnourished patients was significantly lower (p = 0.023) than in non-malnourished patients. Conclusions: Diagnoses of malnutrition according to the GLIM criteria in oncology patients undergoing active treatment predict increased complications and worse survival at 6-month follow-ups, making them a useful tool for assessing the nutritional status of oncology patients.

Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes., Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease., Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models., Results: 167 patients (53% female, 9.6% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4% of patients, requiring initiation of statins in 15%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up., Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population.

Background: Many studies have assessed different malnutrition screening tools in oncologic patients. However, very few have been carried out using the new GLIM criteria for malnutrition. The objective of our study is to compare the most recommended screening tools with respect to the new GLIM criteria for malnutrition in cancer patients., Methods: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department at the Lozano Blesa Hospital in Zaragoza. We recruited 165 patients with tumors of the upper-gastrointestinal-tract, colorectal, and head-and-neck region undergoing outpatient treatment. All of them received MST, MUST, Nutriscore, MNA and CONUT screening tools, as well as the GLIM diagnostic criteria, which was used as the gold standard., Results: MNA-SF showed the best sensitivity (0.99) and lowest specificity while CONUT had the best specificity (0.89) and lowest sensitivity to detect cancer-related malnutrition. We observed high variability in the diagnostic capabilities of Nutriscore when tumor location was considered, reducing sensitivity in patients with colorectal cancer compared to those with tumors of the upper-gastrointestinal-tract or head-and-neck location (0.25, 0.83, and 0.91 respectively). The highest index of agreement between the screening tools was found between MST, MUST and Nutriscore tests. Regarding the GLIM criteria, the highest agreement index was presented by MUST tool (0.66), while CONUT presented the lowest (0.12)., Conclusions: Selecting the screening tool according to the type of cancer and its location may allow us to optimize its use and increase its performance, exploiting the advantages of each of them in the different populations., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

We present the case of a 38-year-old man with no previous medical history who went to the emergency department due to abdominal pain and diarrheal stools with blood of 24 hours of evolution. The patient reports consumption of anti-inflammatories the previous days due to back pain.

Background: Risk for severe COVID-19 increases with age. Different vaccination strategies are currently being considered, including those aimed at slowing down transmission and those aimed at providing direct protection to those most at risk., Methods: The objectives of the current study were i) to assess age-related incidence and survival between PCR-diagnosed COVID-19 cases (n = 61,993) in the Autonomous Community of Aragon from March to November 2020, and ii) to characterize age differences regarding the course of the disease in hospitalized patients in a tertiary university hospital., Results: We found a similar incidence of COVID-19 in individuals between 10 and 79 years. Incidence increased in those over 80 years possibly because of the elevated transmission within the nursing homes. We observed a profound disparity among age groups; case fatality rates (CFRs) were near 0 in cases younger than 39 years throughout different waves. In contrast, there was an age-dependent and progressive increase in the CFRs, especially during the first pandemic wave. SARS-CoV-2 infection caused a more severe and rapid progression in older patients. The elderly required faster hospitalization, presented more serious symptoms on admission, and had a worse clinical course. Hospitalized older individuals, even without comorbidities, had an increased mortality risk directly associated with their age. Lastly, the existence of comorbidities dramatically increased the CFRs in the elderly, especially in males., Conclusion: The elevated incidence of COVID-19 and the vulnerability of the elderly call for their prioritization in vaccination and targeted prevention measures specifically focused on this aged population., Competing Interests: The authors have declared that no competing interests exist.

Background: The use of nutrition-screening tools in cirrhotic patients is not systematized. Recently, specific tools have been proposed for patients with cirrhosis, but their diagnostic capabilities have been scarcely studied., Methods: This was a prospective study that includes outpatients with liver cirrhosis undergoing follow-up in the hepatology consultations of a tertiary-care university hospital. A trained gastroenterologist applied the screening tools: Liver Disease Universal Screening Tool (LDUST), Royal Free Hospital-Nutrition Prioritizing Tool (RFH-NPT), and Mini Nutritional Assessment-Short Form (MNA-SF). Subsequently, the diagnosis of malnutrition was made according to Global Leadership Initiative for Malnutrition (GLIM) criteria by an endocrinologist, who was blind to the results of the screening tools., Results: Sixty-three patients (38.1% women, mean age 63.1 ± 9.9 years) with cirrhosis (60.3% Child-Pugh A, 34.9% Child-Pugh B, and 4.8% Child-Pugh C) were evaluated. The prevalence of malnutrition was 38.1% (15.9% moderate, 22.2% severe). Advanced stages of cirrhosis were associated with a higher prevalence of malnutrition (P = .021). MNA-SF was the most accurate screening tool, being superior to RFH-NPT and LDUST. It presented better sensitivity than RFH-NPT (88% [0.68-0.97] vs 67% [0.45-0.84], P = .031) and better specificity than both LDUST (97% [0.87-0.99] vs 62% [0.45-0.77], P < .001) and RFH-NPT (97% [0.87-0.99] vs 82% [0.67-0.93], P = .016)., Conclusions: According to the GLIM criteria, malnutrition affected 38.1% of patients with cirrhosis, being severe in 22% of the patients. MNA-SF is the most accurate screening test, superior even to tools specifically designed for cirrhotic patients (LDUST)., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab., Aims: To evaluate the impact of biologics on the risk of PC., Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis., Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27)., Conclusions: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

Background & Aims: Malnutrition is one of the most prevalent problems among oncological patients. It reduces the response to treatments and negatively impacts survival. In 2019, a consensus criteria for diagnosing malnutrition (GLIM criteria) were proposed by most scientific nutrition societies. The objective of our work is 1) to assess the diagnostic capacity of the GLIM criteria in ambulatory patients with cancer and 2) to compare the GLIM with the ESPEN criteria to evaluate the contributions of these new criteria with respect to the existing ones., Methods: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department in the Lozano Blesa Clinical Hospital in Zaragoza (Spain). One hundred and sixty-five outpatients with tumors in the upper gastrointestinal tract, head and neck, and colorectal locations were recruited. All of them received the MST, MUST, and Nutriscore screening tools along with the ESPEN and GLIM diagnostic criteria., Results: The prevalence of malnutrition was 46.7% according to the GLIM criteria and 21.2% using the ESPEN tool. Patients diagnosed by GLIM had a higher body mass index (BMI, 24.3 kg/m 2 ) and muscle mass (MM, 16.1 kg/m 2 ) than those diagnosed by ESPEN (21.2 kg/m 2 and 14.3 kg/m 2 respectively, both p = 0.001). The MST, MUST, and Nutriscore tools had a higher degree of concordance with GLIM compared to ESPEN (MST 0.53 vs 0.26; MUST 0.36 vs 0.66; Nutriscore 0.28 vs 0.54)., Conclusions: The found prevalence of malnutrition in cancer patients is higher using the GLIM instead of ESPEN criteria. This disparity can be explained at least in part by the difficulty of the ESPEN criteria for malnutrition to diagnose patients with high baseline BMI or MM. The use of criteria with greater sensitivity, such as the new GLIM criteria, could help early diagnosis and thus early intervention in cancer patients., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Liver and pancreatic diseases have significant consequences on nutritional status, with direct effects on clinical outcomes, survival, and quality of life. Maintaining and preserving an adequate nutritional status is crucial and should be one of the goals of patients with liver or pancreatic disease. Thus, the nutritional status of such patients should be systematically assessed at follow-up. Recently, great progress has been made in this direction, and the relevant pathophysiological mechanisms have been better established. While the spectrum of these diseases is wide, and the mechanisms of the onset of malnutrition are numerous and interrelated, clinical and nutritional manifestations are common. The main consequences include an impaired dietary intake, altered macro and micronutrient metabolism, energy metabolism disturbances, an increase in energy expenditure, nutrient malabsorption, sarcopenia, and osteopathy. In this review, we summarize the factors contributing to malnutrition, and the effects on nutritional status and clinical outcomes of liver and pancreatic diseases. We explain the current knowledge on how to assess malnutrition and the efficacy of nutritional interventions in these settings.

Aim: To evaluate the effectiveness and safety of tofacitinib in ulcerative colitis [UC] in real life., Methods: Patients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score [PMS]. Short-term response/remission was assessed at Weeks 4, 8, and 16., Results: A total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio [OR] = 0].2; 95% confidence interval [CI] = 0].1-0.4) was the only variable associated with lower likelihood of achieving remission at Week 8. Higher PMS at Week 4 [OR = 0.5; 95% CI = 0.3-0.7] and higher PMS at Week 8 [OR = 0.2; 95% CI = 0.1-0.5] were associated with lower probability of achieving remission at Week 16. A total of 45 patients [40%] discontinued tofacitinib over time. Higher PMS at Week 8 was the only factor associated with higher tofacitinib discontinuation [hazard ratio = 1.5; 95% CI = 1.3-1.6]. A total of 34 patients had remission at Week 8; of these, 65% had relapsed 52 weeks after achieving remission; the dose was increased to 10 mg/12 h in nine patients, and five of them reached remission again. Seventeen patients had adverse events., Conclusions: Tofacitinib is effective and safe in UC patients in real practice, even in a highly refractory cohort. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5%) were discharged (109 (20.5%) died). A total of 319 (64.3%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9%) and GGT (47.3%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.

Introduction: Ustekinumab, a monoclonal antibody that blocks interleukins 12/23, has proven in clinical trials its efficacy in inducing and maintaining clinical remission of Crohn's disease (CD). Its effectiveness and safety in actual clinical practice is less known and may differ from trials., Objective: To evaluate its effectiveness and safety in clinical practice (intravenous induction pattern essentially), such as induction and over the long term, in patients with CD refractory to biological treatment., Material and Methods: Multicentre retrospective analysis (6 hospitals in Aragón), which includes all patients (N=69) with CD undergoing treatment with ustekinumab (either with intravenous or subcutaneous induction), who had at least 16 weeks of follow-up. The clinical response or remission has been evaluated at weeks 16, 24, 32 and 48 using the Harvey-Bradshaw index., Results: A total of 69 patients have been included, mean age 42 years, 54% men. A percentage of 89.86 (95% CI [0.805, 0.949]) of the patients presented clinical improvement at week 16 (15.95% remission, 73.92% response). In the subsequent follow-up, this response has been maintained. Age (OR 0.95, P=.028) and smoking habits (OR 0.19, P=.027) have been identified by an ordinal regression model as predictors of poor treatment response while the need for biological change due to adverse effect (OR 96, P=.00017) and due to loss of secondary response (OR 7.07, P=.034) have been predictors of good response. No serious adverse effects have been reported that forced them to stop taking ustekinumab., Conclusion: Ustekinumab is effective and safe in real clinical practice to achieve induction and maintenance of the response in patients with refractory CD. Tobacco and age have been shown to be predictors of poor response, while the indication for adverse effect to previous biological and for loss of secondary response has been shown to be predictors of good response., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)