Philip Hendy reviews Thursz et al. 1The randomized double blind placebo controlled Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial demonstrates that pentoxifylline does not improve mortality in severe alcoholic hepatitis at 28 days or beyond. It also demonstrates that prednisolone provides a non-significant mortality benefit at 28 days which does not persist to 90 days or beyond and is associated with increased risk of infection.
Alcoholic hepatitis is a syndrome characterised by jaundice and liver dysfunction in the setting of significant long-term alcohol excess. Severe disease is associated with high mortality—30% at 1 month and 40% at 6 months.2 ,3 Treatment consists of organ support as required, as well as steroid and or pentoxifylline (PTX) therapy, both of which are included in national and international management guidelines. The European Association for the Study of the Liver guidelines include steroids and, in the case of ongoing sepsis, PTX.4 …
Conclusions: Initial data support the need for, and acceptability of, psychological care in an established IBD service.Psychological screening has been easy to implement, is well accepted, and it uncovers a high need for psychological support in the routine care setting.Longer-term outcomes will inform of potential mental or physical health benefits from this approach.
Abstract Background Intravenous corticosteroids (IVCS) remain the cornerstone of treatment for patients admitted to hospital with Acute Severe Ulcerative colitis (ASUC). Unfortunately, up to one third of patients do not respond to IVCS and need medical or surgical rescue treatment. Identifying patients who are unlikely to respond to IVCS at the point of admission would be clinically relevant since these patients could be offered early rescue treatment, potentially reducing morbidity. Methods This was a post-hoc analysis of a UK multicentre, randomised placebo-controlled trial of Interleukin 1 blockade in Acute Severe Ulcerative Colitis (the IASO trial).1,2 The intervention group did not differ from placebo treated patients in terms of need for rescue therapy or colectomy. Therefore we pooled both groups in this post-hoc analysis. We studied whether clinical symptoms as captured by the modified Truelove and Witts severity index (MTWSI) or its individual components or biochemical parameters at admission to hospital could predict response to IVCS. Results Among 106 randomised patients 68/106 (64%) patients responded to IVCS. 38/106 (36%) were non-responders to IVCS and needed medical rescue treatment (32 infliximab, 6 ciclosporin). Median time to rescue therapy was 4 days (interquartile range: 3-6 days). We observed no differences in baseline MTWSI score or in its individual components (Figure 1) between IVCS responders compared to IVCS non-responders. Baseline median C-reactive protein (CRP) (31.9 mg/L Vs 29.5 mg/L, p= 0.8) and baseline median albumin (36.5 g/L vs 35.0 g/L, p=0.4) were similar between IVCS responders and non-responders. Numerically, patients with higher baseline albumin were less likely to be non-responders to IVCS (upper quartile serum albumin: ≥40.0 g/L, non-responders 23% vs lower 3 quartiles 39% non-responders; p=0.17). 9 patients needed colectomy by day 98, all of whom had a baseline albumin below this threshold. Sensitivity analyses restricted to subpopulations of patients already on oral steroids at admission, those with a new diagnosis of ulcerative colitis, and those randomised to placebo vs anakinra yielded similar results. Conclusion Baseline clinical symptoms at hospitalisation (modified Truelove and Witts severity index and its individual components) and biochemical parameters (CRP and albumin) did not identify patients refractory to IVCS in the IASO trial. These findings suggest that response to IVCS in ASUC cannot be predicted from baseline clinical symptoms and biochemical parameters at admission to hospital. All colectomies occurred in patients with baseline albumin below 40 g/L. References 1.Thomas, M. G. et al. Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial. BMJ Open 9, e023765 (2019). 2.Raine, T. et al. OP33 Results of a randomised controlled trial to evaluate Interleukin 1 blockade with anakinra in patients with acute severe ulcerative colitis (IASO). J. Crohns Colitis 17, i43–i46 (2023).
Summary Background Infliximab and adalimumab have established roles in inflammatory bowel disease ( IBD ) therapy. UK regulators mandate reassessment after 12 months' anti‐ TNF therapy for IBD , with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation. Aim To establish outcomes following anti‐ TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta‐analysis. Methods A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease ( CD ) and 20 with ulcerative colitis [ UC ) and IBD unclassified ( IBDU )] withdrawn from anti‐ TNF for sustained remission. Meta‐analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD , 122 UC ). Results Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD , and 42% by 1 year and 47% by 2 years for UC / IBDU . Increased relapse risk in CD was associated with age at diagnosis [hazard ratio ( HR ) 2.78 for age <22 years], white cell count ( HR 3.22 for >5.25 × 10 9 /L) and faecal calprotectin ( HR 2.95 for >50 μg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta‐analysis, estimated 1‐year relapse rates were 39% and 35% for CD and UC / IBDU respectively. Retreatment with anti‐ TNF was successful in 88% for CD and 76% UC / IBDU . Conclusions Assimilation of all available data reveals remarkable homogeneity. Approximately one‐third of patients with IBD flare within 12 months of withdrawal of anti‐ TNF therapy for sustained remission.
Vitamin D may be immunomodulatory and alter faecal microbiota, but results from clinical studies in humans to date have been inconclusive. This study aimed to assess the effect of vitamin D replacement in vitamin D-deficient patients with and without ulcerative colitis [UC] on inflammation and faecal microbiota.Vitamin D was replaced over 8 weeks in patients with active UC [defined by faecal calprotectin ≥ 100 µg/g], inactive UC [faecal calprotectin < 100 µg/g] and non-inflammatory bowel disease [IBD] controls with baseline serum 25[OH] vitamin D <50 nmol/l, and markers of inflammation and faecal microbiota were analysed.Eight patients with active UC, nine with inactive UC and eight non-IBD controls received 40000 units cholecalciferol weekly for 8 weeks. Mean baseline 25[OH] vitamin D increased from 34 [range 12-49] to 111 [71-158] nmol/l [p < 0.001], with no difference across the groups [p = 0.32]. In patients with active UC, faecal calprotectin levels decreased from a median 275 to 111 µg/g [p = 0.02], platelet count decreased [mean 375 to 313 × 109/l, p = 0.03] and albumin increased [mean 43 to 45 g/l, p = 0.04]. These parameters did not change in patients with inactive UC or non-IBD controls. No changes in overall faecal bacterial diversity were noted although a significant increase in Enterobacteriaceae abundance was observed in patients with UC [p = 0.03].Vitamin D supplementation was associated with reduced intestinal inflammation in patients with active UC, with a concomitant increase in Enterobacteriaceae but no change in overall faecal microbial diversity.
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