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Summary Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose‐optimisation for ustekinumab nonresponse is limited. Aim To assess the effectiveness of dose escalation of ustekinumab. Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard‐dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation. Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose‐escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid‐free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow‐up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow‐up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission. Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.

Background The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn’s disease is in sharp contrast to its widespread use in clinical practice. Aims The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn’s disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease. Methods In a European community-based inception cohort, 488 patients with Crohn’s disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists. Results Overall, 292 (60%) patients with Crohn’s disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6–60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)). Conclusion In this European community-based inception cohort of unselected Crohn’s disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn’s disease, its use seems to result in a satisfying disease course for both patients and physicians.

Background We aimed to determine if there was a higher incidence of small intestinal bacterial overgrowth (SIBO) in non‐alcoholic fatty liver disease (NAFLD) than in patients without NAFLD. Moreover, we assessed whether patients with significant fibrosis (SF) had a higher incidence of SIBO compared with patients with non‐significant or no liver fibrosis. Methods NAFLD was diagnosed in 117 patients by using Fibroscan with a controlled attenuation parameter (CAP) as well as liver biopsy (LB). SIBO was defined by esophagogastroduodenoscopy with an aspiration of the descending duodenum. Results Patients with non‐alcoholic steatohepatitis (NASH) and those with SF on LB had a significantly higher incidence of SIBO than patients without NASH and those without SF, respectively (P < .05). According to histological characteristics, there was a higher proportion of patients in the SIBO group with higher steatosis and fibrosis grade, lobular and portal inflammation, and ballooning grade (P < .001). In multivariate analysis, significant predictors associated with SF and NASH were type 2 diabetes mellitus (T2DM) and SIBO. Moreover, in multivariate analysis, significant predictors that were independently associated with SIBO were T2DM, fibrosis stage and ballooning grade (OR 8.80 (2.07‐37.37), 2.50 (1.16‐5.37) and 27.6 (6.41‐119), respectively). The most commonly isolated were gram‐negative bacteria, predominantly Escherichia coli and Klebsiella pneumoniae. Conclusion In this relatively large population of patients, we used a gold standard for both SIBO (quantitative culture of duodenum's descending part aspirate) and NAFLD (LB), and we demonstrated that NASH patients and those with SF had a higher incidence of SIBO. Moreover, significant predictors independently associated with SIBO were T2DM, fibrosis stage and ballooning grade. Although TE is a well‐investigated method for steatosis and fibrosis detection, in our study, independent predictors of SIBO were histological characteristics of NAFLD, while elastographic parameters did not reach statistical significance.

The link between metabolic syndrome (MetS) and sarcopenia has not been extensively studied, but it is evident that they share several common features. Crucial mechanisms involved in sarcopenia-nonalcoholic fatty liver disease (NAFLD) interplay are based on effects of insulin resistance, chronic inflammation, oxidative stress, and crosstalk between organs by secretion of cytokines (hepatokines, adipokines, and myokines). Currently, published studies confirm the association of sarcopenia with the degree of NAFLD defined by liver histology. However, prospective studies that will give us information regarding the causal effect of NAFLD and sarcopenia are still needed. Furthermore, there is a need for a patient-friendly, noninvasive, low-cost method for detection of loss of skeletal muscle mass, strength, and physical performance in the context of NAFLD. Moreover, potential treatment strategies such as physical exercise and nutritional supplementation, that are usually a part of management of sarcopenia, should also be investigated in NAFLD patients, especially given the fact that for now, we do not have a good treatment option for NAFLD. Therefore, future investigations should combine studies on NAFLD and sarcopenia in terms of physical activity and nutritional interventions such as vitamin D supplementation. This review aims to report recent evidence concerning the links between sarcopenia and NAFLD and methods to assess sarcopenia.