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Dr. Alastair O'Brien

Alastair O'Brien

Research interests

My research is directed towards combating infection in acute decompensation liver disease patients (AD). Having documented the extremely poor outcome for AD in intensive care (ICU), I believe the greatest gain will be achieved by tackling the major cause of ICU admission from the ward, infection, which is due to immune suppression. I have combined molecular science, clinical studies and large scale data analysis in order to pursue this. My research group consists of a post-doctoral research fellow, 3 PhD students, a data manager, clinical research nurse and clinical trial team at the UCL Comprehensive Clinical Trials Unit. This is funded by The Wellcome Trust, Department of Health,  Medical Research Council and Biotechnology and Biological Sciences Research Council.
My work identified the first molecular mechanism (elevated Prostaglandin E2, (PGE2) to explain immune suppression in AD patients (Nature Medicine). Importantly I identified that albumin could antagonise PGE2 which led to my randomised controlled trial (ATTIRE) to test whether albumin can prevent infection and improve mortality (www.attiretrial.com). This is the largest interventional study currently recruiting worldwide in patients with advanced liver disease at 30 hospitals (866 patients) throughout the UK. This will complete November 2018.

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Selected Publications

  1. China L, Skene S, Shabir Z, Maini A, Sylvestre Y, Bennett K, Bevan S, O’Beirne J, Forrest E, Portal J, Ryder S, Wright G, Gilroy DW & O’Brien AJ. Administration of Albumin Solution Increases Serum Levels of Albumin in Patients with Chronic Liver Failure in a Single-arm Feasibility Trial. Clin Gastroenterol Hepatol. 2017 Sep 12. pii: S1542-3565(17)31098-4. [Epub ahead of print]
  2. China L, Maini A, Skene S, Shabir Z, Sylvestre, Colas R, Ly L, Becares Salles N, Belloti V, Dalli J, Gilroy DW & O’Brien AJ. Albumin Counteracts Immune-suppressive Effects of Lipid Mediators in Patients With Advanced Liver Disease. Clin Gastroenterol Hepatol. 2017 Aug 28. pii: S1542-3565(17)30993-X. doi: 10.1016/j.cgh.2017.08.027. [Epub ahead of print]
  3. ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for a single-arm feasibility trial. China L, Muirhead N, Skene SS, Shabir Z, De Maeyer RP, Maini A, Gilroy DW, O'Brien AJ. BMJ Open. 2016 Jan 25;6(1):e010132.
  4. Shallcross L, O'Brien A. Antimicrobial resistance in liver disease: better diagnostics are needed. Lancet Gastroenterol Hepatol. 2017 Mar;2(3):151-153.
  5. Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. O'Brien AJ, Fullerton JN, Massey KA, Auld G, Sewell G, James S, Newson J, Karra E, Winstanley A, Alazawi W, Garcia-Martinez R, Cordoba J, Nicolaou A, Gilroy DW. Nature Medicine. 2014;20(5):518-23.
  6. O'Brien AJ, Welch CA, Singer, M, Harrison DA.  Prevalence and outcome of cirrhosis patients admitted to UK intensive care. A comparison against dialysis-dependent chronic renal failure patients. Intensive Care Med. 2012; 38:991-1000.

Keywords

Liver cirrhosis, Immune suppression, Eicosanoids, Albumin