Publications
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Nathwani R, Mukherjee S, Forlano R, et al., 2020, Letter: liver disease and COVID-19 - not the perfect storm, Alimentary Pharmacology and Therapeutics, Vol: 52, Pages: 572-574, ISSN: 0269-2813
This article is linked to Garrido et al papers. To view these articles, visit https://doi.org/10.1111/apt.15813 and https://doi.org/10.1111/apt.15886.
Rhodes F, Cococcia S, Vergis N, et al., 2019, AN ALGORITHM COMBINING HYALURONIC ACID, PROCOLLAGEN III AMINO-TERMINAL PEPTIDE AND THE GLASGOW ALCOHOLIC HEPATITIS SCORE IN A SINGLE NUMBER PREDICTS 90-DAY MORTALITY IN ALCOHOL-RELATED HEPATITIS., Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 817A-818A, ISSN: 0270-9139
Vergis N, Thursz M, Atkinson S, 2019, Assessment and management of infection in alcoholic hepatitis, Seminars in Liver Disease, Vol: 40, Pages: 11-19, ISSN: 0272-8087
Severe alcoholic hepatitis (SAH) is a condition characterized by jaundice and liver failure that develops after heavy and prolonged alcohol consumption. Infection frequently complicates the natural history of the disease and is independently associated with mortality. Objective recognition and recording of infection are therefore essential in the evaluation of therapeutic interventions and for antibiotic stewardship. This review will evaluate infections that complicate SAH at admission and beyond. Factors that associate with the development of infection will be identified and clinical and laboratory techniques available to identify infection will be discussed. Common pathogens and frequently used antibiotics will be reviewed and recommendations will be made for the management of infection for SAH patients. New techniques to assess infection earlier and more precisely may improve diagnosis and treatment of this important driver of mortality in SAH.
Forrest EH, Storey N, Sinha R, et al., 2019, Baseline neutrophil-to-lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis., Alimentary Pharmacology and Therapeutics, Vol: 50, Pages: 442-453, ISSN: 0269-2813
BACKGROUND: Treating severe alcoholic hepatitis involves the exposure of patients to corticosteroids for 7 days to assess "response". AIM: To assess the prognostic and therapeutic implications of baseline Neutrophil-to-Lymphocyte ratio (NLR) in patients with severe alcoholic hepatitis. METHODS: Patients recruited to the STOPAH trial and an independent validation group were analysed retrospectively. Area under the Receiver Operating Curve (AUC) analysis was performed. Kaplan-Meier analysis was used to assess survival. Log-rank test and Odds ratio (OR) were used for comparative analysis. RESULTS: Baseline NLR was available for 789 STOPAH patients. The AUC for NLR was modest for 90-day outcome (0.660), but it was associated with infection, acute kidney injury (AKI) and severity of alcoholic hepatitis. Ninety-day survival was not affected by prednisolone treatment if NLR < 5 or > 8 < 5 but mortality was reduced with prednisolone treatment when the NLR was 5-8:21.0% cf. 34.5%; P = 0.012. Prednisolone treatment increased the chance of Lille response if the NLR was ≥ 5 (56.5% cf. 41.1%: P = 0.01; OR 1.86) but increased the risk of Day 7 infection (17.3% cf. 7.4%: P = 0.006; OR 2.60) and AKI (20.8% cf. 7.0%: P = 0.008; OR 3.46) if the NLR was > 8. Incorporation of NLR into a modified Glasgow Alcoholic Hepatitis Score (mGAHS) improved the AUC to 0.783 and 0.739 for 28-day and 90-day outcome, respectively. CONCLUSION: The NLR is associated with AKI and infection in severe alcoholic hepatitis. The NLR identifies those most likely to benefit from corticosteroids at baseline (NLR 5-8). The mGAHS has a good predictive value for 28- and 90-day outcomes.
Parker R, Kim SJ, Im GY, et al., 2019, Obesity in acute alcoholic hepatitis increases morbidity and mortality, EBioMedicine, Vol: 45, Pages: 511-518, ISSN: 2352-3964
BackgroundAlcohol and obesity synergise to increase the risk of liver-related mortality. We examined the influence of adiposity on clinical outcomes in alcoholic hepatitis (AH) and the underlying inflammatory crosstalk between adipose tissue (AT) and the liver.MethodsA cohort of 233 patients with AH from the UK and USA provided data to analyse the effects of obesity in AH. Body mass index was corrected for the severity of ascites, termed cBMI. Inflammatory and metabolic profiling was undertaken by proteome analysis of human serum samples. The effect of alcohol on adipose tissue and CXCL11 expression was studied in 3 T3-derived adipocytes and in mice using the high-fat diet-plus-binge ethanol model.FindingsObesity was common amongst patients with AH, seen in 19% of individuals. Obesity (HR 2.22, 95%CI 1.1–4.3, p = .022) and underweight (HR 2.38, 1.00–5.6, p = .049) were independently associated with mortality at 3 months. Proteome analysis demonstrated multiple metabolic and inflammatory factors differentially expressed in obese AH verse lean AH, with CXCL11 being the most elevated factor in obese AH. In vitro analysis of cultured adipocytes and in vivo analysis of mouse models showed that alcohol induced CXCL11 expression in AT, but not in liver.InterpretationObesity is common in AH and associated with a greater than two-fold increase in short-term mortality. Obese AH is associated with a different inflammatory phenotype, with the greatest elevation in CXCL11. These data confirm that adiposity is clinically important in acute alcohol-related liver disease and illustrate the adipose-liver inflammatory axis in AH.FundThis work was supported in part by an EASL Sheila Sherlock Physician Scientist Fellowship. The funder played no role in gathering or analysing data or writing the manuscript. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the U
Tyson LD, Atkinson S, Pechlivanis A, et al., 2019, Serum bile acid profiles distinguish severe alcoholic hepatitis from decompensated alcohol-related cirrhosis, International Liver Congress, Publisher: ELSEVIER SCIENCE BV, Pages: E108-E108, ISSN: 0168-8278
Vergis N, Atkinson S, Thursz M, 2019, The future of therapy for alcoholic hepatitis - beyond corticosteroids, Journal of Hepatology, Vol: 70, Pages: 785-787, ISSN: 0168-8278
Corticosteroids are the only treatment proven to reduce mortality from severe alcoholic hepatitis (SAH), though the benefit is short-lived.1 Several potential therapies are currently under evaluation in human clinical trials (Table 1). These therapies target: i) malnutrition; ii) intestinal dysbiosis and its portal translocation; iii) bile acid production; iv) hepatocyte death; v) hepatocyte regeneration; and vi) life-threatening complications of the disease itself.
Forrest E, Storey N, Sinha R, et al., 2019, Baseline neutrophil-to-lymphocyte ratio indicates both prevalent and incident infection and acute kidney injury, and is related to corticosteroid Lille response in alcoholic hepatitis, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E47-E47, ISSN: 0168-8278
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Forrest E, Storey N, Sinha R, et al., 2019, A modified Glasgow alcoholic hepatitis score incorporating the neutrophil-to-lymphocyte ratio is superior to other baseline scores of prognosis in alcoholic hepatitis, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E277-E278, ISSN: 0168-8278
Vergis N, Scarborough AJ, Morris JA, et al., 2018, Prone or Left for Colonoscopy? A Randomized Controlled Trial of Prone Versus Left-sided Starting Position for Colonoscopy, JOURNAL OF CLINICAL GASTROENTEROLOGY, Vol: 52, Pages: E82-E86, ISSN: 0192-0790
Atkinson SR, Vergis N, Louvet A, et al., 2017, Universal screening of acute medical admissions for excess alcohol consumption: What's the misuse?, JOURNAL OF HEPATOLOGY, Vol: 67, Pages: 448-450, ISSN: 0168-8278
Atkinson S, Maurice J, Vergis N, et al., 2017, SERUM PROCALCITONIN CORRELATES WITH BASELINE RENAL FUNCTION AND PREDICTS MORTALITY IN SEVERE ALCOHOLIC HEPATITIS, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A167-A167, ISSN: 0017-5749
Atkinson SR, Maurice J, Vergis N, et al., 2017, Serum procalcitonin correlates with baseline renal function and predicts mortality in severe alcoholic hepatitis, International Liver Congress / 52nd Annual Meeting of the European-Association-for-the-Study-of-the-Liver, Publisher: ELSEVIER SCIENCE BV, Pages: S117-S117, ISSN: 0168-8278
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Vergis N, Atkinson SR, Knapp S, et al., 2016, In patients with severe alcoholic hepatitis, prednisolone increases susceptibility to infection and infection-related mortality, associated with high circulating levels of bacterial DNA, Gastroenterology, Vol: 152, Pages: 1068-1077.e4, ISSN: 0016-5085
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
Atkinson S, Vergis N, Thursz M, 2016, INFECTION IN SEVERE ALCOHOLIC HEPATITIS: RESULTS FROM THE STOPAH TRIAL, GUT, Vol: 65, Pages: A274-A275, ISSN: 0017-5749
Vergis N, Atkinson SR, Maurice JB, et al., 2016, IDENTIFYING PATIENTS WITH ELEVATED CIRCULATING BACTERIAL DNA MAY REDUCE INFECTION AND DEATH IN ALCOHOLIC HEPATITIS, GUT, Vol: 65, Pages: A20-A21, ISSN: 0017-5749
Vergis N, McGrath AK, Stoddart CH, et al., 2016, Reply to Kaif et al., American Journal of Gastroenterology, Vol: 111, Pages: 1035-1035, ISSN: 1572-0241
Vergis N, McGrath AK, Stoddart CH, et al., 2016, Right-versus Conventional Left-Sided Starting Position for Colonoscopy: The Issues to Be Considered Reply, AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol: 111, Pages: 897-898, ISSN: 0002-9270
Scarborough AJ, Morris JA, Vergis N, et al., 2016, PRONE OR LEFT STARTING POSITION FOR COLONOSCOPY? A RANDOMISED CONTROLLED TRIAL, Publisher: BMJ PUBLISHING GROUP, Pages: A218-A219, ISSN: 0017-5749
Vergis N, McGrath AK, Stoddart CH, et al., 2016, Right Lateral Decubitus for Routine Colonoscopy: Beware the Potential Risk of Aspiration Reply, AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol: 111, Pages: 899-899, ISSN: 0002-9270
Morris J, Scarborough AJ, Vergis N, et al., 2016, Prone or Left Starting Position for Colonoscopy (POLCOL)? A Randomised Controlled Trial, DDW ASGE Meeting, Publisher: MOSBY-ELSEVIER, Pages: AB535-AB536, ISSN: 0016-5107
Vergis N, Khamri W, Gill US, et al., 2016, Effect of prednisolone therapy on monocyte phenotype and function in alcoholic hepatitis, Spring Meeting on Clinician Scientists in Training, Publisher: ELSEVIER SCIENCE INC, Pages: 103-103, ISSN: 0140-6736
Vergis N, Khamri W, Beale K, et al., 2016, Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase, Gut, Vol: 66, Pages: 519-529, ISSN: 1468-3288
Objective In order to explain the increasedsusceptibility to serious infection in alcoholic hepatitis,we evaluated monocyte phagocytosis, aberrations ofassociated signalling pathways and their reversibility, andwhether phagocytic defects could predict subsequentinfection.Design Monocytes were identified from blood samplesof 42 patients with severe alcoholic hepatitis usingmonoclonal antibody to CD14. Phagocytosis andmonocyte oxidative burst (MOB) were measured ex vivousing flow cytometry, luminometry and bacterial killingassays. Defects were related to the subsequentdevelopment of infection. Intracellular signallingpathways were investigated using western blotting andPCR. Interferon-γ (IFN-γ) was evaluated for itstherapeutic potential in reversing phagocytic defects.Paired longitudinal samples were used to evaluate theeffect of in vivo prednisolone therapy.Results MOB, production of superoxide and bacterialkilling in response to Escherichia coli were markedlyimpaired in patients with alcoholic hepatitis.Pretreatment MOB predicted development of infectionwithin two weeks with sensitivity and specificity thatwere superior to available clinical markers. Accordingly,defective MOB was associated with death at 28 and90 days. Expression of the gp91phox subunit ofnicotinamide adenine dinucleotide phosphate (NADPH)oxidase was reduced in patients with alcoholic hepatitisdemonstrating defective MOB. Monocytes were refractoryto IFN-γ stimulation and showed high levels of anegative regulator of cytokine signalling, suppressor ofcytokine signalling-1. MOB was unaffected by 7 days invivo prednisolone therapy.Conclusions Monocyte oxidative burst and bacterialkilling is impaired in alcoholic hepatitis while bacterialuptake by phagocytosis is preserved. Defective MOB isassociated with reduced expression of NADPH oxidase inthese patients and predicts the development of infectionand death.
Abeles RD, Antoniades C, Manakkat-Vijay G, et al., 2016, MODULATION OF THE NON-CANONICAL NFKB PATHWAYS MAY UNDERLIE ALTERNATIVE ACTIVATION OF CIRCULATING CD14HI MONOCYTES IN HYPER-ACUTE LIVER FAILURE, EASL International Liver Congress, Publisher: ELSEVIER SCIENCE BV, Pages: S311-S312, ISSN: 0168-8278
Khamri W, Abeles D, Hou T, et al., 2016, CTLA-4 IS A NEGATIVE REGULATOR OF T CELL ACTIVATION IN ACUTE LIVER FAILURE, EASL International Liver Congress, Publisher: ELSEVIER SCIENCE BV, Pages: S152-S152, ISSN: 0168-8278
Atkinson S, Vergis N, Thursz M, 2016, INFECTION IN SEVERE ALCOHOLIC HEPATITIS: RESULTS FROM THE STOPAH TRIAL, EASL International Liver Congress, Publisher: ELSEVIER SCIENCE BV, Pages: S174-S175, ISSN: 0168-8278
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Vergis N, Khamri W, Antoniades C, et al., 2016, HIGH FREQUENCY OF INFLAMMATORY CD16+MONOCYTES IN ALCOHOLIC HEPATITIS CAN BE REDUCED BY TREATMENT WITH PREDNISOLONE, EASL International Liver Congress, Publisher: ELSEVIER SCIENCE BV, Pages: S238-S238, ISSN: 0168-8278
Vergis N, McGrath AK, Stoddart CH, et al., 2015, Right Or Left in COLonoscopy (ROLCOL)? A Randomized Controlled Trial of Right- versus Left-Sided Starting Position in Colonoscopy, AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol: 110, Pages: 1576-1581, ISSN: 0002-9270
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- Citations: 22
Petts G, Lloyd K, Vergis N, et al., 2015, The Liver Biopsy in Alcoholic Hepatitis: Data from the Steroids or Pentoxifylline in Alcoholic Hepatitis (STOPAH) Clinical Trial, 8th Joint Meeting of the British-Division of the International-Academy-of-Pathology and the Pathological-Society-of-Great-Britain-and-Ireland, Publisher: WILEY-BLACKWELL, Pages: S23-S23, ISSN: 0022-3417
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Beale K, Vergis N, Sadiq F, et al., 2015, MONOCYTE OXIDATIVE BURST DEFECT IN ALCOHOLIC HEPATITIS IS RESISTANT TO INTERFERON GAMMA, 2nd Digestive-Disorders-Federation Conference, Publisher: BMJ PUBLISHING GROUP, Pages: A450-A450, ISSN: 0017-5749
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