Evaluating the role of antibiotics in patients admitted to hospital With decompensated cirrhosis: Lessons from the ATTIRE trial

INTRODUCTION: Hospital-acquired infections (HAI) are common in cirrhosis with antibiotics frequently used to prevent infections, but their efficacy for this role is unknown. To investigate this, we used Albumin to Prevent Infection in Chronic Liver Failure (ATTIRE) data to evaluate whether antibiotic use in patients without infection prevented HAI. METHOD(S): In ATTIRE patients without infection at baseline grouped by antibiotic prescription or not, we studied HAI during trial treatment period and mortality, with propensity score matching to account for differences in disease severity. RESULT(S): Two hundred three of 408 patients prescribed antibiotics at enrollment did not have infection and they were more unwell than noninfected patients not given antibiotics. There were no differences in subsequent HAI comparing antibiotic treated (39/203, 19.2%) to nonantibiotic treated (73/360, 20.3%; P = 0.83). Twenty-eight-day mortality was higher in antibiotic-treated patients ( P = 0.004) likely reflecting increased disease severity. Matching groups using propensity scoring revealed no differences in HAI or mortality. In noninfected patients at enrollment treated with/without rifaximin, there were no differences in HAI ( P = 0.16) or mortality, confirmed with propensity matching. Patients given long-term antibiotic prophylaxis at discharge had no differences in 6-month mortality compared with nonantibiotic patients, although antibiotic-treated patients had more infections at trial entry, with numbers too small for matching. DISCUSSION: Half of antibiotics at study entry were given to patients without an infection diagnosis which did not reduce the overall risk of HAI or improve mortality. This supports prompt de-escalation or discontinuation of antibiotics guided by culture sensitivities at 24-48 hours after commencement if no infection and the patient is improving.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.https://doi.org/10.14309/ajg.000000000000193

The relationship between disease activity and UDCA response criteria in primary biliary cholangitis: A cohort study

BACKGROUND: Uncertainty exists about how best to identify primary biliary cholangitis (PBC) patients who would benefit from second-line therapy. Existing, purely clinical, ursodeoxycholic acid (UDCA) response criteria accept degrees of liver biochemistry abnormality in responding patients, emerging data, however, suggest that any degree of ongoing abnormality may, in fact, be associated with an increased risk of adverse outcomes. This cohort study explores the link between response status, the biology of high-risk disease and its implications for clinical practice. METHODS: Proteomics, exploring 19 markers previously identified as remaining elevated in PBC following UDCA therapy, were performed on 400 serum samples, from participants previously recruited to the UK-PBC Nested Cohort between 2014 and 2019. All participants had an established diagnosis of PBC and were taking therapeutic doses of UDCA for greater than 12 months. UDCA response status was assessed using Paris 1, Paris 2 and the POISE criteria, with additional analyses using normal liver blood tests stratified by bilirubin level. Statistical analysis using parametric t tests and 1-way ANOVA. FINDINGS: Disease markers were statistically significantly higher in UDCA non-responders than in responders for all the UDCA response criteria, suggesting a meaningful link between biochemical disease status and disease mechanism. For each of the criteria, however, marker levels were also statistically significantly higher in responders with ongoing liver function test abnormality compared to those who had normalised their liver biochemistry. IL-4RA, IL-18-R1, CXCL11, 9 and 10, CD163 and ACE2 were consistently elevated across all responder groups with ongoing LFT abnormality. No statistically significant differences occurred between markers in normal LFT groups stratified by bilirubin level. INTERPRETATION: This study provides evidence that any ongoing elevation in alkaline phosphatase levels in PBC after UDCA therapy is associated with some degree of ongoing disease activity. There was no difference in activity between patients with normal LFT when stratified by bilirubin. These findings suggest that if our goal is to completely control disease activity in PBC, then normalisation of alkaline phosphatase and bilirubin should be the treatment target. This would also simplify messaging around goals of therapy in PBC, benefiting both patients and clinicians. FUNDING: Funding by the UK Medical Research Council (Stratified Medicine Programme) and an independent research grant by Pfizer. The study funders played no role in the study design, data collection, data analyses, data interpretation or manuscript writing. Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.https://doi.org/10.1016/j.ebiom.2022.10406

In Patients With Severe Alcoholic Hepatitis, Prednisolone Increases Susceptibility to Infection and Infection-Related Mortality, and Is Associated With High Circulating Levels of Bacterial DNA

Background & Aims Infections are common in patients with severe alcoholic hepatitis (SAH), but little information is available on how to predict their development or their effects on patients. Prednisolone is advocated for treatment of SAH, but can increase susceptibility to infection. We compared the effects of infection on clinical outcomes of patients treated with and without prednisolone, and identified risk factors for development of infection in SAH. Methods We analyzed data from 1092 patients enrolled in a double-blind placebo-controlled trial to evaluate the efficacy of treatment with prednisolone (40 mg daily) or pentoxifylline (400 mg 3 times each day) in patients with SAH. The 2 × 2 factorial design led to 547 patients receiving prednisolone; 546 were treated with pentoxifylline. The trial was conducted in the United Kingdom from January 2011 through February 2014. Data on development of infection were collected at evaluations performed at screening, baseline, weekly during admission, on discharge, and after 90 days. Patients were diagnosed with infection based on published clinical and microbiologic criteria. Risk factors for development of infection and effects on 90-day mortality were evaluated separately in patients treated with prednisolone (n = 547) and patients not treated with prednisolone (n = 545) using logistic regression. Pretreatment blood levels of bacterial DNA (bDNA) were measured in 731 patients. Results Of the 1092 patients in the study, 135 had an infection at baseline, 251 developed infections during treatment, and 89 patients developed an infection after treatment. There was no association between pentoxifylline therapy and the risk of serious infection (P = .084), infection during treatment (P = .20), or infection after treatment (P = .27). Infections classified as serious were more frequent in patients treated with prednisolone (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.27−2.92; P = .002). There was no association between prednisolone therapy and infection during treatment (OR, 1.04; 95% CI, 0.78−1.37; P = .80). However, a higher proportion (10%) of patients receiving prednisolone developed an infection after treatment than of patients not given prednisolone (6%) (OR, 1.70; 95% CI, 1.07−2.69; P = .024). Development of infection was associated with increased 90-day mortality in patients with SAH treated with prednisolone, independent of model for end-stage liver disease or Lille score (OR, 2.46; 95% CI, 1.41−4.30; P = .002). High circulating bDNA predicted infection that developed within 7 days of prednisolone therapy, independent of Model for End-Stage Liver Disease and white blood cell count (OR, 4.68; 95% CI, 1.80−12.17; P = .001). In patients who did not receive prednisolone, infection was not independently associated with 90-day mortality (OR, 0.94; 95% CI, 0.54−1.62; P = .82) or levels of bDNA (OR, 0.83; 95% CI, 0.39−1.75; P = .62). Conclusions Patients with SAH given prednisolone are at greater risk for developing serious infections and infections after treatment than patients not given prednisolone, which may offset its therapeutic benefit. Level of circulating bDNA before treatment could identify patients at high risk of infection if given prednisolone; these data could be used to select therapies for patients with SAH. EudraCT no: 2009-013897-42; Current Controlled Trials no: ISRCTN88782125

Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE)

Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs

The United Kingdom and British Empire: A Figurational Approach

Drawing upon the work of Norbert Elias and the process [figurational] sociology perspective, this article examines how state formation processes are related to, and, affected by, expanding and declining chains of international interdependence. In contrast to civic and ethnic conceptions, this approach focuses on the emergence of the nation/nation-state as grounded in broader processes of historical and social development. In doing so, state formation processes within the United Kingdom are related to the expansion and decline of the British Empire. That is, by focusing on the functional dynamics that are embedded in collective groups, one is able to consider how the UK’s ‘state’ and ‘imperial’ figurations were interdependently related to changes in both the UK and the former British Empire. Consequently, by locating contemporary UK relations in the historical context of former imperial relationships, nationalism studies can go ‘beyond’ the nation/nation-state in order to include broader processes of imperial expansion and decline. Here, the relationship between empire and nationalism can offer a valuable insight into contemporary political movements, especially within former imperial groups

Exploring changing attitudes to non-invasive liver fibrosis tests in secondary care pathways: comparison of two national surveys

INTRODUCTION: The increasing availability of non-invasive tests (NITs) has created the opportunity to explore their use in improving risk stratification of advanced liver disease. The study aimed to determine the attitudes and practices among UK secondary care specialists, focusing primarily on attitudes to fibrosis assessment and the use of NITs. METHODS: Two web-based surveys were circulated, first between 2014 and 2015 (survey 1), and again in 2021 (survey 2). The surveys were promoted via the British Society of Gastroenterology, the British Association for the Study of the Liver and using Twitter. RESULTS: In survey 1, 215 healthcare professionals (HCPs) completed the online survey. 112 HCPs completed survey 2. 71 acute UK trusts were represented in survey 1 compared with 60 trusts in survey 2. Between the two surveys, the proportion of HCPs performing fibrosis assessment in all or nearly all cases rose from 45.1% to 74.1% (χ2=25.01; p<0.0001). 46.5% (n=33/71) respondents in acute services reported the use of NITs in clinical pathways in survey 1, rising to 70.0% (n=42/60) in survey 2 (χ2=7.35; p=0.007). Availability of tests has increased but is not universal. The proportion reporting availability as a barrier to uptake fell from 57.2% of responses in survey 1 to 38.4% in 2021 χ2=11.01; p=0.0009). CONCLUSION: Between 2014 and 2021, the role of NITs in fibrosis assessment has risen substantially, as has the proportion of clinicians using NITs in clinical pathways to assess risk of liver disease. Poor access to NITs remains the predominant barrier

Characteristics of alcohol recovery narratives: Systematic review and narrative synthesis

Background and aims Narratives of recovery from alcohol misuse have been analysed in a range of research studies. This paper aims to produce a conceptual framework describing the characteristics of alcohol misuse recovery narratives that are in the research literature, to inform the development of research, policy, and practice. Methods Systematic review was conducted following PRISMA guidelines. Electronic searches of databases (Ovid MEDLINE, EMBASE, CINHAL, PsychInfo, AMED and SCOPUS), grey literature, and citation searches for included studies were conducted. Alcohol recovery narratives were defined as "first-person lived experience accounts, which includes elements of adversity, struggle, strength, success, and survival related to alcohol misuse, and refer to events or actions over a period of time". Frameworks were synthesised using a three-stage process. Sub-group analyses were conducted on studies presenting analyses of narratives with specific genders, ages, sexualities, ethnicities, and dual diagnosis. The review was prospectively registered (PROSPERO CRD42021235176). Results 32 studies were included (29 qualitative, 3 mixed-methods, 1055 participants, age range 17-82years, 52.6% male, 46.4% female). Most were conducted in the United States (n = 15) and Europe (n = 11). No included studies analysed recovery narratives from lower income countries. Treatment settings included Alcoholic Anonymous (n = 12 studies), other formal treatment, and 'natural recovery'. Eight principle narrative dimensions were identified (genre, identity, recovery setting, drinking trajectory, drinking behaviours, stages, spirituality and religion, and recovery experience) each with types and subtypes. All dimensions were present in most subgroups. Shame was a prominent theme for female narrators, lack of sense of belonging and spirituality were prominent for LGBTQ+ narrators, and alienation and inequality were prominent for indigenous narrators. Conclusions Review provides characteristics of alcohol recovery narratives, with implications for both research and healthcare practice. It demonstrated knowledge gaps in relation to alcohol recovery narratives of people living in lower income countries, or those who recovered outside of mainstream services.Copyright: © 2022 Subhani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.https://doi.org/10.1371/journal.pone.026803