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ObjectiveImmune paresis in patients with acute-on-chronic liver failure (ACLF) accounts for infection susceptibility and increased mortality. Immunosuppressive mononuclear CD14+HLA-DR− myeloid-derived suppressor cells (M-MDSCs) have recently been identified to quell antimicrobial responses in immune-mediated diseases. We sought to delineate the function and derivation of M-MDSC in patients with ACLF, and explore potential targets to augment antimicrobial responses.DesignPatients with ACLF (n=41) were compared with healthy subjects (n=25) and patients with cirrhosis (n=22) or acute liver failure (n=30). CD14+CD15−CD11b+HLA-DR− cells were identified as per definition of M-MDSC and detailed immunophenotypic analyses were performed. Suppression of T cell activation was assessed by mixed lymphocyte reaction. Assessment of innate immune function included cytokine expression in response to Toll-like receptor (TLR-2, TLR-4 and TLR-9) stimulation and phagocytosis assays using flow cytometry and live cell imaging-based techniques.ResultsCirculating CD14+CD15−CD11b+HLA-DR− M-MDSCs were markedly expanded in patients with ACLF (55% of CD14+ cells). M-MDSC displayed immunosuppressive properties, significantly decreasing T cell proliferation (p=0.01), producing less tumour necrosis factor-alpha/interleukin-6 in response to TLR stimulation (all p<0.01), and reduced bacterial uptake of Escherichia coli (p<0.001). Persistently low expression of HLA-DR during disease evolution was linked to secondary infection and 28-day mortality. Recurrent TLR-2 and TLR-4 stimulation expanded M-MDSC in vitro. By contrast, TLR-3 agonism reconstituted HLA-DR expression and innate immune function ex vivo.ConclusionImmunosuppressive CD14+HLA-DR− M-MDSCs are expanded in patients with ACLF. They were depicted by suppressing T cell function, attenuated antimicrobial innate immune responses, linked to secondary infection, disease severity and prognosis. TLR-3 agonism reversed M-MDSC expansion and innate immune function and merits further evaluation as potential immunotherapeutic agent.

IntroductionThe ‘Hub and Spoke’ model for hepatology care has been implemented nationally to reduce variation in patient care and improve access to liver transplantation and specialist services. This model typically involves transferring patients from regional hospitals (spokes) to tertiary liver centres (hubs). However, rising pressures on NHS hospital bed spaces impacts this approach. A pilot study was conducted to investigate the benefits of reversing the ‘Hub and Spoke’ model, with hepatologists from the Royal Free Hospital (hub) providing in-person consults to patients at Barnet Hospital (spoke).MethodBetween June 3 and September 2, 2024, twice-weekly in-person, consultant-led hepatology ward rounds were conducted for liver-related admissions. Data was collected and compared to outcomes from the same period in 2023. Trainee experience was assessed via electronic feedback questionnaires.Results134 patients were reviewed. During the pilot, median time to specialist review from admission was 22 hours. Average length of stay was 13.25 days for patients with cirrhosis. All cirrhotics had follow-up appointments arranged, averaging 21 days post-discharge. The 28-readmission rate was 24% on discharge, with only 1/13 patients having an avoidable admission for ascitic drain insertion. Fewer referrals were made between Barnet and Royal Free Hospitals, 4 vs 22 in 2023. 4 patients were transferred to the Royal Free, compared to 12 the previous year. Other differences observed between 2023 and 2024 are summarised in table 1.Feedback from the 12 Barnet Hospital gastroenterology team members indicated that hepatology in-reach improved patient care, reduced the need for referral to the Royal Free Hospital, facilitated earlier discharge and enhanced follow-up planning. Resident doctors reported better support in managing liver patients and improved their hepatology training. Feedback also demonstrated that patients with liver related admissions in the ‘spoke site’ had better access to specialist meetings, potentially impacting patient outcomes.Abstract P337 Table 1Differences observed between 2023 vs 2024 2023 2024 Median time to specialist review from admission 78 hours 22 hours Average length of stay for patients with cirrhosis 17.5 days 13.25 days Follow up not arranged for patients with cirrhosis 31% 0% Average time to follow up in patients with cirrhosis 42 days 21 days 28-day readmission 25% 24% Readmissions for ascitic drains within 28 days (n) 41.6% (5/12) 7.7% (1/13) ConclusionThis pilot study demonstrates the positive impact of providing hepatology in-reach consults to ‘spoke’ district general hospitals from the ‘hub’ tertiary centre. With improvement to patient care, it has the potential to alleviate clinical and resource pressures whilst improving hepatology training.

Although metabolic risk factors are associated with more severe COVID-19, there is little evidence on outcomes in patients with non-alcoholic fatty liver disease (NAFLD). We here describe the clinical characteristics and outcomes of NAFLD patients in a cohort hospitalised for COVID-19. This study included all consecutive patients admitted for COVID-19 between February and April 2020 at Imperial College Healthcare NHS Trust, with either imaging of the liver available dated within one year from the admission or a known diagnosis of NAFLD. Clinical data and early weaning score (EWS) were recorded. NAFLD diagnosis was based on imaging or past medical history and patients were stratified for Fibrosis-4 (FIB-4) index. Clinical endpoints were admission to intensive care unit (ICU)and in-hospital mortality. 561 patients were admitted. Overall, 193 patients were included in the study. Fifty nine patients (30%) died, 9 (5%) were still in hospital, and 125 (65%) were discharged. The NAFLD cohort (n = 61) was significantly younger (60 vs 70.5 years, p = 0.046) at presentation compared to the non-NAFLD (n = 132). NAFLD diagnosis was not associated with adverse outcomes. However, the NAFLD group had higher C reactive protein (CRP) (107 vs 91.2 mg/L, p = 0.05) compared to non-NAFLD(n = 132). Among NAFLD patients, male gender (p = 0.01), ferritin (p = 0.003) and EWS (p = 0.047) were associated with in-hospital mortality, while the presence of intermediate/high risk FIB-4 or liver cirrhosis was not. The presence of NAFLD per se was not associated with worse outcomes in patients hospitalised for COVID-19. Though NAFLD patients were younger on admission, disease stage was not associated with clinical outcomes. Yet, mortality was associated with gender and a pronounced inflammatory response in the NAFLD group.

In this case of complex anticoagulation, a 60-year-old woman was treated with low-molecular-weight heparin for pulmonary embolism. As a result of anticoagulation, she then developed an acute subdural haemorrhage identified on CT brain scan requiring craniectomy. Subsequently, while continuing anticoagulation for treatment for pulmonary embolism, she additionally had a large intra-abdominal bleed within and around the psoas muscle identified on abdominal CT scan. Although the increased risk of bleeding is known with anticoagulation therapy, the case of both an intracerebral and intra-abdominal bleed is rare. However, the case does highlight how each individual has a unique physiological response to anticoagulation, in some cases more severe than others.

IntroductionThe burden of liver disease in the UK continues to rise, with the Office for Health Improvement and Disparities (OHID) finding a 22% increase in liver related hospital admissions in 2022 compared to 2021. We aimed to evaluate the referrals received at the Royal Free Hospital, a tertiary hepatology and liver transplant centre; describing rationale of referral, patient demographics and the types of referring centres.MethodsThis retrospective study was conducted over a 15-month period between 1st September 2023-30th November 2024. Data was extrapolated from an electronic referrals database and the Trustwide Electronic Patient Referrals (EPR) system. The British Association for the Study of the Liver (BASL) website was used to identify the Hepatology Level of the referring centre.Results1031 referrals were received at the Royal Free Hospital from referring centres, with 229 being transferred (22.2%). 69 referrals were made per month with approximately 15 of those being transferred. Figure 1 describes the breakdown of referrals received by category, and by how many were transferred. There were 594 (57.6%) males and 437 (42.4%) females referred. The average age of a patient referred was 54.2 years. There were 90 centres referring to RFH, with 50 (55.6%) being Level 1 Hepatology Centres, 10 (11.1%) being Enhanced Level 1, 29 (32.2%) being Level 2 and 1 (0.01%) being a Level 3 centre.Abstract P344 Figure 1ConclusionsThis observational study highlights the significant volume of patients referred to a typical tertiary level hepatology centre of which there are only 7 nationally. The majority of the referrals are due to chronic liver disease and its sequalae, with variceal bleeding being the leading cause of cases transferred. With a rising national and global prevalence, and a known disparity existing in the burden of liver disease and access to speciality care, we may need to reconsider how hepatology care is delivered to level 1 and level 2 hepatology centres in order to ensure equity in care.

IntroductionAs more specialists become dual accredited in internal medicine, non-gastroenterology specialists have greater exposure to gastroenterology patients over the course of their training, especially via the acute take. Simultaneously, the COVID pandemic has meant most regular local teaching has moved online with varying quality. This project aimed to evaluate 1) whether a standardised protocol can be used to successfully deliver large scale digital gastroenterology teaching that 2) is non-inferior when compared with traditional face to face teaching.MethodsTeaching was delivered to internal medical trainees on the acute management of ulcerative colitis and chronic liver disease. Two sessions were delivered a year apart, initially regionally, and then nationally. This was delivered via Zoom, using a standardised protocol based on guidelines to ensure consistency, with live-polled multiple-choice questions to encourage interaction. Each session was followed by Q&A related to that topic. Feedback was taken after each session. Outcome measures analysed were: number in attendance, whether viewers would recommend this teaching to others, whether they thought it ran smoothly, and how they felt about it when compared with face-to-face teaching as measured on a Likert scale. Given the subjective nature of our hypotheses, we accept that these are surrogate markers.Results171 trainees attended the initial regional teaching session and 469 the subsequent session. Following the first session, 98.9% of trainees would recommend the teaching to others, rising to 99.7% after the second session. 99% and 99.5% respectively agreed or strongly agreed with the statement the initial session ran smoothly, while 84.5% and 88.8% agreed or strongly agreed that digital teaching was as effective as face to face. The benefits of digital teaching were no travel (90%) ability to watch later (86%), whereas the downsides were loss of social interaction (60%) and harder to get study leave (39%).ConclusionsGastroenterology teaching for non-specialists can be delivered successfully at a large scale using a standardised protocol for digital teaching. The vast majority of trainees felt that digital sessions were as effective as face-to-face teaching with a lack of travel and flexibility on viewing time the main reported benefits.

ObjectiveIdentifying components of immuneparesis, a hallmark of chronic liver failure, is crucial for our understanding of complications in cirrhosis. Various suppressor CD4+ T cells have been established as potent inhibitors of systemic immune activation. Here, we establish the presence, regulation and mechanism of action of a suppressive CD4+ T cell subset expressing human leucocyte antigen G (HLA-G) in patients with acute decompensation of cirrhosis (AD).DesignFlow cytometry was used to determine the proportion and immunophenotype of CD4+HLA-G+ T cells from peripheral blood of 20 healthy controls (HCs) and 98 patients with cirrhosis (28 with stable cirrhosis (SC), 20 with chronic decompensated cirrhosis (CD) and 50 with AD). Transcriptional and functional signatures of cell-sorted CD4+HLA-G+ cells were delineated by NanoString technology and suppression assays, respectively. The role of immunosuppressive cytokine interleukin (IL)-35 in inducing this population was investigated through in vitro blockade experiments. Immunohistochemistry (IHC) and cultures of primary human Kupffer cells (KCs) were performed to assess cellular sources of IL-35. HLA-G-mediated T cell suppression was explored using neutralising antibodies targeting co-inhibitory pathways.ResultsPatients with AD were distinguished by an expansion of a CD4+HLA-G+CTLA-4+IL-35+ immunosuppressive population associated with disease severity, clinical course of AD, infectious complications and poor outcome. Transcriptomic analyses excluded the possibility that these were thymic-derived regulatory T cells. IHC analyses and in vitro cultures demonstrate that KCs represent a potent source of IL-35 which can induce the observed HLA-G+ phenotype. These exert cytotoxic T lymphocyte antigen-4-mediated impaired responses in T cells paralleled by an HLA-G-driven downregulation of T helper 17-related cytokines.ConclusionWe have identified a cytokine-driven peripherally derived suppressive population that may contribute to immuneparesis in AD.

Table 1 Baseline characteristics of NSBB users and non-users attending a specialist cirrhosis clinic at St Mary’s Hospital, London, UK Demographics NSBB (n=89) Non-NSBB (n=49) P value Sex (%) 0.39  Male 64 (71.9) 31 (63.3)  Female 25 (28.1) 18 (36.7) Age (years) (IQR) 58 (49–66) 59 (52–67) 0.47  Main aetiology (%) 0.52  Alcohol 48 (53.9) 31 (63.3)  Hepatitis C 16 (18.0) 7 (14.3)  Non-alcoholic steatohepatitis 6 (6.7) 6 (12.2) Disease severity (IQR)  Child-Pugh Score 8 (8–10) 8 (7–10) 0.39  Model For End-Stage Liver Disease score 13.50 (11.40–15.80) 11.80 (9.40–14.40) 0.006 Ascites (%)  None 38 (42.7) 17 (34.7) 0.12  Mild 24 (27.0) 9 (18.4)  Moderate 18 (20.2) 11 (22.4)  Severe 9 (10.1) 12 (24.5) Hepatic encephalopathy (%) 24 (27.0) 10 (20.4) 0.52 Hepatocellular carcinoma (%) 6 (6.7) 1 (2.0) 0.42 Laboratory parameters (IQR)  Sodium (mmol/L) 137 (133–139) 137 (135–138) 0.91  Creatinine (μmol/L) 70 (62–84) 63 (57–73) 0.03  Albumin (g/L) 29 (25–33) 30 (26–33) 0.33  Bilirubin (µmol/L) 39 (23–59) 30 (15–52) 0.06  International normalised ratio 1.3 (1.2–1.5) 1.3 (1.2–1.4) 0.03  Platelets (×109/L) 96 (66–144) 127 (83–136) 0.03 NSBB, non-selective beta blocker. Table 2 Baseline characteristics of patients with bDNA according to the use of NSBB Demographics NSBB group (n=11) Non-NSBB group (n=11) P value Age (years) (IQR) 57 (51–68) 51 (44–56) 0.14 Gender, % (n) 0.65  Male sex 63.6 (7/11) 72.7 (8/11)  Female sex 36.4 (4/11) 27.3 (3/11) Aetiology, % (n)  Alcoholic liver disease 54.5 (6/11) 72.7 (8/11) 0.38  Viral hepatitis (hepatitis B or C) 27.3 (3/11) 9.1 (1/11) 0.27 Non-alcoholic steatohepatitis 18.2 (2/11) 18.2 (2/11) 1.00 Model For End-Stage Liver Disease score (IQR) 14.9 (11.4–19.9) 14.5 (12.7–23.1) 0.72 Comorbidities, % (n)  Ischaemic heart disease 9.1 (1/11) 9.1 (1/11) 1.00  Lung disease 18.2 (2/11) 18.2 (2/11) 1.00  Diabetes mellitus 36.4 (4/11) 18.2 (2/11) 0.34 Primary infection site, % (n)  Spontaneous bacteraemia 27.3 (3/11) 36.4 (4/11) 0.65  Spontaneous bacterial peritonitis 18.2 (2/11) 9.1 (1/11) 0.53  Respiratory infection 27.3 (3/11) 18.2 (2/11) 0.61  Cellulitis – 18.2 (2/11) –  Urinary tract infection 18.2 (2/11) – –  Other abdominal infections 9.1 (1/11) 18.2 (2/11) 0.53 bDNA, bacterial DNA; NSBB, non-selective beta blocker. [...]we agree with Jachs et al that in clinical trials involving cirrhotic patients, where inflammatory/infective outcome measures are being assessed, consideration needs to be given to patient stratification by NSBB use to allow optimal study design and interpretation of results. [...]infections independently increase mortality in hospitalized patients with cirrhosis: the North American Consortium for the study of end-stage liver disease (NACSELD) experience.