Background and AimAlcohol-related liver disease (ALD) remains a leading cause of liver-related morbidity and mortality. Age, fibrosis stage, MELD score and continued alcohol consumption predict outcome in everyday clinical practice. In previous studies increased hepatocyte nuclear area and hepatocyte expression of p21, both markers of senescence, were associated with increased fibrosis stage and a poor outcome in non-alcohol-related fatty liver disease, while increased hepatocyte nuclear area was related to liver dysfunction in ALD cirrhosis. This study, therefore, investigated the pattern of hepatocyte cell cycle phase distribution and hepatocyte p21 expression in relation to outcome in ALD.MethodsLiver sections from two cohorts were studied. The first comprised 42 patients across the full spectrum of ALD. The second cohort comprised 77 patients with ALD cirrhosis. Immunohistochemistry assessed hepatocyte expression of cell cycle phase markers and p21. Regenerating liver (n=12) and “normal” liver sections (n=5) served as positive and negative controls, respectively.ResultsIn the first cohort there was little cell cycle progression beyond G1/S phase and increased hepatocyte p21 expression (p<0.0001), which correlated independently with fibrosis stage (p=0.005) and an adverse liver-related outcome (p=0.03). In the second cohort, both hepatocyte p21 expression (p<0.001) and MELD score (p=0.006) were associated independently with an adverse liver-related outcome; this association was stronger with hepatocyte p21 expression (AUROC 0.74; p=0.0002) than with MELD score (AUROC 0.59; p=0.13). Further, hepatocyte p21 expression co-localised with increased hepatic stellate cell activation.ConclusionsThe findings are consistent with impaired cell cycle progression beyond the G1/S phase in ALD. The striking independent associations between increased hepatocyte p21 expression and both fibrosis stage and an adverse liver-related outcome in both cohorts suggests hepatocyte senescence plays an important role in ALD. Measuring hepatocyte p21 expression is simple and cheap and in this series was a useful measure of long-term prognosis in ALD.

The 5-lipoxygenase data provide a cellular basis for increased tissue synthesis of the leukotriene B(4), as reflected in the colonic mucosa and rectal dialysates of patients with active inflammatory bowel disease, which contributes to neutrophil influx and colonic injury. The COX-1/COX-2 data highlight the ambiguous functional role of prostanoid pathways in inflammatory bowel diseases.

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IntroductionSwitching from an established biologic to a biosimilar to save costs was considered likely to be ‘inappropriate and ineffective’ by ECCO.1MethodsWith Area Prescribing Committee approval, all Crohns disease (CD) patients established on Remicade were provided with written and verbal information regarding the proposed switch, and all patients infused after April 2015 received Inflectra. Baseline calprotectin and Infliximab antibody and trough levels were undertaken. Harvey Bradshaw Indices (HBI) were assessed at every 8 week infusion.Results21 CD patients were already established on Remicade treatment. 1 patient did not receive Inflectra as he was relapsing with high antibody and low trough levels. 4 other patients with high antibody levels (>10iU/L) did receive Inflectra, but increasing symptoms led to alternative immunosuppression in 3 of these patients (2 with Adalumimab, 1 with Allopurinol/Azathioprine). A decision was made just to stop infliximab in the 4’th pt as they were in full clinical remission. The results of the remaining 16 patients are illustrated below.ConclusionAlthough this is a small dataset, early results are encouraging. Patients understood the rationale behind the switch. There were no significant adverse events as a consequence of the switch. The majority of patients either remained in clinical remission or improved during the follow up period. The annual confirmed cost savings of £220,000 permitted investment in further IBD nurse monitoring (0.5 WTE) and allowed the introduction of infliximab trough and antibody testing which has certainly optimised and rationalised treatment decisions in these complex patients.Abstract PTU-059 Figure 1Changes in HBIAbstract PTU-059 Figure 2CalprotectionReference1 Danese S, et al. ECCO position statement: the use of biosimilar medicines in the treatment of IBD. J Crohns Colitis 2013;7(7): 586–9.Disclosure of InterestNone Declared